Advances in Statin Therapy & Beyond in CVD (ASTC): A Textbook of Cardiology Praveen Chandra, Navin C Nanda, HK Chopra, GS Wander, Viveka Kumar, AK Pancholia, Jagat Narula, CN Manjunath, CK Ponde
INDEX
Page numbers followed by b refer to box, f refer to figure, fc refer to flowchart, and t refer to table.
A
Abdominal aneurysm 456, 459
repair 459
Abdominal aortic aneurysm 102, 178, 284, 458, 448, 674
pathogenesis of 458
Abdominal obesity 52, 291
Abdominal pain 290
Acceleration index 681
Acetylcholine 335
Acid derivative 98
Acquired immunodeficiency syndrome 4, 19, 713
Acromegaly 89
Activated nicotinamide adenine dinucleotide phosphate oxidase 771
Acute coronary
events 343
heart disease 185
Acute coronary syndrome 1113, 26, 32, 44, 45, 54, 74, 103, 115, 117, 144, 238, 282, 317, 320, 321, 323, 324, 328, 329, 332, 333, 342, 344f, 347, 349, 361, 368, 420, 430, 431, 450, 452, 497, 538, 548, 592, 699, 610, 735737, 794, 795, 802, 842, 855, 857, 858, 867, 869, 873, 884, 887, 887t, 910
development of 317
history of 534
pathogenesis of 321
secondary prevention of 318
statin in 45, 322, 325
Acute ischemic stroke 468
statin in 45
Acute kidney
failure 230
injury 284, 376, 348, 818
Acyl-coenzyme A cholesterol acyltransferase inhibitors 751
Ad hoc analysis 364
Adaptive intimal thickening 582
Adenine dinucleotide phosphate 317
Adenosine triphosphate 524, 892
citrate lyase 250, 863, 848
Adhesion molecules 317, 452, 810
Adipocyte 303
derived renin-angiotensin-aldosterone system 404
Adipogenesis 169
effects on 544
Adipose tissue 179
dysregulation 545
Adjunct nonstatin therapy 735
Adult treatment panel 45
Aerobic exercises 83
Aggressive lipid lowering 104, 592
initiation 570
Air
pollution 76
purifiers 333
Airway epithelium, structural hallmark of 786
Airway smooth muscle proliferation 786
Alanine aminotransferase 74, 167, 213, 518, 739, 795, 803
activity of 350
Alanine transaminase 285
Albumin 21
Albuminuria 21, 99, 284
Alcohol 82, 135, 141, 291
abuse, history of 418
consumption 81, 174, 397
excessive 82, 290
high 289
moderate 82
use 433
Alcoholism 81, 89
Alipogene tiparvovec 252
Alirocumab 10, 28, 47, 68, 351, 361, 362, 364, 497, 750, 839, 862, 867, 873t, 875, 883
Alpha-linolenic acid 707
Alveolar epithelial cells 788
Alzheimer's dementia 716
Alzheimer's disease 145, 146, 221, 222, 225, 264, 439
Amino acids 89
Aminotransferase elevation, risk of 157
Amiodarone 66, 68, 83, 85, 163, 567, 739, 812
Amlodipine 66, 739
Amlodipine monotherapy 399
Ampulla cardiomyopathy 378
Anacetrapib 255
Androgen excess, signs of 204
Aneurysm 50
growth rate 458
rupture rate 459
Angina 5, 335, 794
pectoris 335, 712
Angiogenesis 132, 133, 133f, 657
attenuation of 133
biphasic effects on 132
control of 134
Angiography 594
Angioplasty 115, 420
Angiopoietin-1 133
Angiopoietin-like protein 3 127, 250, 862
inhibitor 863, 912
Angiotensin 133, 196, 448, 453, 639
Angiotensin receptor
antagonists 567
blockers 186, 573, 816
neprilysin inhibitors 415
subtype 195
Angiotensin-converting enzyme 245, 453
inhibitors 186, 415, 573
Angiotensins 135
ANKDD1A gene 245
Ankle-brachial index 5, 37, 237, 512, 545, 581, 735
Anorexia nervosa 86
Anthocyanins 357
Antiarrhythmic drugs 433
Antiatherogenic agents 333
Antiatherosclerotic vascular protection 453
Anticoagulant therapy 465
Antidepressant effects 154
Antihyperlipidemic therapy 209
Antihypertensive medications 386
Antihypertensive treatment 400
Anti-inflammatory actions 421
Anti-inflammatory agents 147, 774
role of 452
Anti-inflammatory cytokine 93
interleukin 220
Anti-inflammatory effect 181, 195, 468, 716718, 810
Anti-inflammatory molecule 257
Anti-inflammatory pleiotropic effects 93
Anti-inflammatory property 93, 197
Antioxidant 224, 399, 717, 727
effect 166, 195, 716
enzymes 190
Antiplatelet 465
Anti-proprotein convertase subtilsinkexin 9 monoclonal antibodies 875t
Antipsychotics 89
Antiretroviral therapy 10, 89
Antisense oligonucleotide 69, 215, 301, 309, 884, 910
therapy 301
Antithrombotic agents 343
Antithrombotic effect 65, 431
Aorta 447, 448, 452
abdominal 668f
aneurysm, descending 457
ascending 457
atherosclerosis of 453
Aortic aneurysm 452
management of 453
reduced growth of 674
statin in 448
Aortic arch 667f
Aortic arterial stiffness 448
Aortic atheromatous plaques 447
Aortic atherosclerosis 303, 447, 452, 667, 670672
statin therapy in 453
Aortic atherosclerotic
plaque 227, 447, 451
statin effect evaluation 665
Aortic disease 456
statin in 445
Aortic distensibility 595, 671, 673f
measurement of 595
Aortic stenosis 219, 456, 457, 606, 607, 607f, 608
congenital 608
progression 457, 608
Aortic transcatheter valve, placement of 457
Aortic valve
area 607
calcification 606, 607
leaflets 607f
opening 647
replacement 606
Aortic vessel wall thickness 672
Aortic wall 458
stiffness 673
volume 667
Apheresis 301
Apical ballooning cardiomyopathy 378
Apo E gene 337
Apolipoprotein 67, 69, 73, 77, 162, 250, 451
A 68
AI 303
ratios 78
B 4, 7, 13, 18, 21, 36, 37, 78, 96, 100, 137, 272, 312, 367, 434, 512, 861, 862, 919
containing lipoproteins 94
gene 328
measurements of 18
B-100 14
E 243
levels of 129
Apoprotein 330
Apoptosis 165
delaying 420
prone for 699
reduction in 443
Apoptotic pathways 494
Arcus corneae 85
Arcus senilis 780, 780f
Arrhythmia 111, 202, 267, 433, 699
Arrhythmogenesis, suppression of 420
Arterial diameter change 595
Arterial distensibility 595
Arterial fibrillation 402
Arterial lumen 684f
narrowing of 481
obliteration of 684
stenosis 481
Arterial revascularization 842
Arterial stiffness 447, 448, 450, 594596
basic principles of 594
early-age 473
index 595
local 595
measurement of 594
Arterial strain 595
Arterial wall 184, 266
Arteriogenesis 494
Arteriosclerotic cardiovascular disease 736
Artery
flow waveform 680f
segmental 680f
stiffening of 684
thrombosis, large 474
wall of 582f
Arthralgias 850
Asialoglycoprotein receptor 301, 895
ASNSD1 gene 245
Aspartate aminotransferase 79, 167, 220, 803
Aspergillus terreus 72, 122, 405, 515, 733
Aspirin 615, 652
Asthma 83, 220, 785, 786, 789
Astrocytes 465
Asymmetric dimethylarginine 180, 379
Atherogenesis 138, 332, 528f, 660f
effects on 544
low risk of 431
Atherogenic dyslipidemia 9, 32, 122, 290, 753, 755, 866, 919
Atherogenic lipids 116
Atherogenic lipoprotein 27, 65, 322
Atheroma 118, 271, 481
calcification in 612f
formation of 482
plaque volume 334
regression 801
volume 592
large 344
Atheromatous plaque
evaluation of 694
formation 447
structure of 582f
Atherosclerosis 25, 50, 54, 81, 85, 91, 93, 137, 138, 139fc, 144, 146, 184, 196, 225, 259, 266, 279, 334, 361, 393, 404, 422, 447, 448fc, 452, 493, 496, 510, 581, 583, 591, 599, 610, 612, 657, 670, 671, 674, 699, 700f, 702
cardiovascular disease 25
cause of 351
conventional imaging of 701
development of 184, 200, 266
disease progression 65
in young diabetes 510
marker of subclinical 582
pathogenesis of 282, 528, 554f
pathology of 657
pathophysiology of 200, 201fc, 267fc, 537
prevention of 201, 267
process 593
progression 116, 584
regression of 342, 584
reversal of 556, 592, 738
trials 856
risk in community study 582, 834
statin-induced regression of 588
stress-induced 138
Atherosclerotic areas 481
Atherosclerotic cardiovascular disease 4, 9, 21, 30, 37t, 39, 46, 61, 76, 81, 94, 115, 126, 194, 204, 218, 237, 247, 251, 257, 272, 282, 293, 296, 303, 312, 332, 353, 367, 385, 390, 402, 450, 473, 510, 517, 533, 538, 548, 566, 597, 606, 622, 657, 707, 734, 752, 758, 793, 802, 840, 859, 866, 873, 875, 884, 886t, 887, 891, 900, 905, 912
development of 329, 385
prevention of 355, 534
primary prevention of 36, 36fc, 298, 533, 734
progression of 452
risk categories for 333t
risk factor for 18
risk of 3, 67, 271, 386
secondary prevention of 296, 734
treatment of 194
Atherosclerotic carotid
artery plaque 487f
disease 599
Atherosclerotic coronary artery disease 329
Atherosclerotic disease 38, 200, 266, 376, 471, 493, 597
prevention of 322
Atherosclerotic formation 486
Atherosclerotic heart disease 418
Atherosclerotic lesion 188, 259
progression of 196
Atherosclerotic origin 38, 76, 390
Atherosclerotic peripheral vascular disease 493
Atherosclerotic plaque 197, 329, 342, 447, 450f, 451, 494f, 583f, 589f, 691
formation 342f, 453
imaging 693
inflammation 694f
instability 399
regression, statin-induced 591
stability 183
stabilization of 65
statin effect on 275
strategy of 701
unstable 342
visualization of 276
Atherosclerotic process 67, 275, 481, 482f, 679
Atherosclerotic progression 376
Atherosclerotic risk 871
Atherosclerotic vascular disease 493
risk factors for 494, 495fc
Atherothrombosis 494
Atherothrombotic events, prevention of 330
Atherothrombotic strokes 466
Atorva 44
Atorvastatin 11, 39, 44, 56, 72, 97, 105, 108, 115, 123, 128, 130, 144, 153f, 158, 165, 170, 187, 202, 205t, 207, 214, 220, 236, 247, 262, 269, 283, 318, 325, 330, 343, 349, 375, 398, 405, 434, 438, 459, 475, 487, 524, 529, 538, 562, 567, 570, 584, 591, 652, 737, 759, 793, 794t, 796, 812, 835, 858
combination therapy 286
comparative cholesterol efficacy 243
efficacy of high-dose 349
high doses of 93, 130, 284, 349
meta-analysis of 795t
role of 795
therapy 185
treatment 619f
trials 793
use of 419
ATP-binding cassette 718
Atrial fibrillation 93, 163, 192, 218, 219t, 232, 283, 374, 429, 708, 921
new-onset 11
statin therapy in 429
Atrial samples, right 192
Attitudes 140
Auditory brainstem 208, 209
Autocrine functions 194
Autoimmune
liver injury 157
myopathy 149
statin-induced 356
uveitis 774
Autonomic nervous system 135
Autosomal dominant hypercholesterolemia 882
Autosomal recessive disorder 337
Axial sodium fluoride 696f
Azole antifungals 812
B
B cells, activated 180
B lymphocytes 93
Back pain 849
Bacteremia 821
Bacterium 787
Ballooning 156
Barbiturates 567
Bariatric surgery 920, 920t, 921
effects of 919, 920
role of 918
types of 920
Bempedoic acid 41, 57, 69, 215, 252, 307, 308, 352, 353, 583, 850, 848, 851, 862, 863, 878, 880, 891, 892f, 894, 897, 911, 912
adverse events of 850
indications of 252
mechanism of action of 892f
pharmacokinetics of 878
side effects of 850b
Bempedoic drug trials 912t
Berberine 357
Berberol 357
Best medical therapy 599
Beta-adrenergic blocking agents 89
Beta-blockers 83, 86, 652, 713
Biallelic mutations 252
Bicuspid aortic valve 456, 457
Bile acid 86, 99
binding resins 167
sequestrant 4, 99, 215, 749
Bioprosthetic valve degeneration 232
Black blood 671
Bloating 749
Blocking synthesis 363
Blood
concentrations 137
glucose 521, 553
lipid levels 82
lipid profile 137
Blood cholesterol 51f, 184
high 187, 511
management of 422
therapeutic targets for 540t
Blood pressure 31, 219, 369, 399, 402, 408, 505, 528, 888, 919
control of 398
diastolic 141, 397, 402, 595
elevated 919
high 554
systolic 9, 141, 397, 402, 595
Blood sugar 292
high 628
Blood-brain barrier 466
Bococizumab 361, 364, 750
Body mass index 52, 82, 553, 556, 752, 918
high 76
Bone
growth 716
morphogenetic protein 191, 221
Brachial artery
dimension 196
flow-mediated dilatation 581
Bradykinin 178
receptor 638
Brain 174
injury, traumatic 822
natriuretic peptide 626
Breast 718
cancer 262, 264
resistance protein 257
Breastfeeding 803
Breath, shortness of 420
Broken heart syndrome 378
Bronchial asthma 140
Bronchiectasis 787, 789
Budesonide 220
Bull's eye
map 644
plot 643f646f
Burns 89
Bypass surgery 141
C
C reactive protein 437, 817
C receptor gene 337
Caffeine 135, 141
Calcific aortic
stenosis 606
valve stenosis 299
Calcineurin inhibitors 565
Calcium
antagonists 567, 812
channel blockers 123
density 57, 372
depicts 277
homeostasis, abnormal 415
mass 611
Cancer 62, 221, 258, 264, 268, 357, 359, 713, 717
cells, apoptosis in 718
incidence of 225
treatment 833
Capillary basal membrane 473
Carbohydrate 54, 55
abnormalities 169
diets
high 55
low 55
sources of 82
Carboxylation 192
Cardiac amyloidosis 648f
Cardiac arrest, resuscitated 268
Cardiac complication 458
Cardiac death 267, 416
Cardiac diastolic function 716
Cardiac disease 218, 321
Cardiac event, major adverse 45, 48, 62, 644, 873
Cardiac hypertrophy 190, 218, 443
Cardiac illness 429
Cardiac intensive care
statin therapy in 235
unit 239
Cardiac muscle, lesions of 132
Cardiac myocytes 429
Cardiac resynchronization therapy 441
Cardiac surgery 192, 219, 429, 712
Cardiac transplant 875
Cardiac valves 456
Cardiomyocytes 378
Cardiomyopathy
family history of 418
stress-induced 378
Cardio-oncology, statin in 831
Cardiothoracic surgeries 820
Cardiovascular complications 842
prevention of 419
risk of 398
Cardiovascular death 66, 481
Cardiovascular disease 16, 25, 38, 57, 65, 76, 81, 97, 102, 108, 115, 135, 144, 149, 164, 175, 219, 224, 239, 262, 266, 271, 281, 289, 293, 299, 303, 311, 312t, 325, 351, 361, 367, 391, 400, 404, 408, 433, 450, 516, 527, 542, 553, 565, 569, 581, 635, 642, 691, 707, 734, 753, 759, 801, 804, 848, 860, 869, 891, 900, 918, 919
development of 753
high-dose statins in 102
low-dose statins in 102
predictors of 179
premature atherosclerotic 299
prevention of 130, 274, 465, 520, 799
primary 767
prevention of 539t
risk factors for 164f, 594
risk of 200, 299, 561
role in 711
secondary 767
prevention of 63, 539t
sign of 146
statin
for primary prevention of 108
for tertiary prevention of 114
reduce 488
Cardiovascular disorders 133
Cardiovascular drugs 242
Cardiovascular effects 561
Cardiovascular event 126, 475
major adverse 323, 566, 795, 828, 855, 880, 884, 887
prevention of 232, 441
risk of 82
Cardiovascular heart disease 408
Cardiovascular morbidity, effect on 347, 438
Cardiovascular mortality 355, 505
effect on 347, 438
higher risk of 495
Cardiovascular outcome trials 902
Cardiovascular prevention
secondary 715
trials 25, 26t
Cardiovascular risk 262
assessment of 405, 511t
Cardiovascular system 169
Carotenes 727
Carotenoids 719
Carotid artery 484, 589f, 657
atheroma 483
atherosclerotic disease 486
B-mode ultrasound of 588
distal common 589f
internal 583, 590, 658, 659
intima, higher 510
intimal-medial thickness 588
surgery 233
ultrasound of 657
Carotid artery disease 279, 481, 483, 488, 597, 598
management of 599fc
statin in 598
Carotid artery stenosis 233, 483, 486, 597, 598t, 599
asymptomatic 598
pathophysiology of 486
Carotid atherosclerosis 661
Carotid bifurcation 583, 590
Carotid disease, asymptomatic 599
Carotid endarterectomy 233, 487
Carotid interventions 599
Carotid intima 481, 487, 581
media thickness 196, 481, 483, 561, 581, 582f, 590, 612, 657, 658, 660
severity grading of 483t
statin in 481
Carotid plaque 481, 484f, 657, 658, 660
evaluation of 657
passivation 597
quality 660
quantification of 658
vulnerability of 660b
Carotid revascularization 469
Carotid stenosis 660
severe 600
Carotid surgery trial, asymptomatic 599
Carotid ultrasound imaging 598
Cascade screening 15, 753
Catalase 190
Catalyzes intracellular esterification 751
Cataract 268, 774
incidence of 269
Catecholamines 136
Causing thrombosis 317
Cavernosal artery 685f
Cavernosal endothelial dysfunction 153
Cell
adhesion 770
molecules 342, 486
control 770
division autoantigen 1 574
functions 456
membrane 195, 816f
maintenance 257
part of 85
migration 132
proliferation 770, 809
Cellular adhesion molecules 487
Cellular development 770
Cellular mediators 194
Cellular redox signalling, disruption of 190
Cellular respiration 203
Central nervous system 135, 833
Central obesity 86
Cephalin 722
Cerebral amyloid angiopathy 834
Cerebral arterioles 465
Cerebral artery 597
occlusion 466
Cerebral ischemia 470
Cerebral small vessel disease 465
Cerebrovascular disease 50, 143, 303, 385, 473, 833
history of 230
Cerivastatin 72, 124, 180, 185, 195, 520, 567
Chanarin-Dorfman syndrome 780
Charlson comorbidity index 321
Cheaper drugs 63
Chemoattractant proteins 810
Chemokines 452
CHI3L2 gene 245
Cholangitis 172
Cholecystectomy 172
Cholecystitis 172
Cholecystokinin 86
Cholestasis 86
Cholesterol 18, 50, 54, 61, 81, 85, 91, 97, 104, 172, 174, 175, 228, 230, 236, 257, 262, 303305, 307, 405, 433, 493, 557, 561, 571, 584, 683, 723, 727, 809, 920
concentration 83, 267
confusion 227
coronary connection 227
de novo synthesis of 152
designs 91
efflux capacity 891
forming atheromas 684f
gallstones 172
hypothesis 228
in ischemia 343
intake 82
lipids including 85
lipoproteins 51, 54t
management 237, 517
metabolism 88f, 919
modifying therapies 303
molecule 733
paradox 119
reduction 335, 496
rich lipoprotein 289
stones 172
synthesis of 333
treatment trialists 200, 261, 266, 276, 297, 322, 347, 438, 548, 736, 855
Cholesterol absorption 79
effect on 718
inhibitors 97, 347, 749
Cholesterol and
atherosclerosis 227
fetal development 174
recurrent events 375
Cholesterol and triglyceride 178
management of high 291
Cholesterol biosynthesis 94, 170, 172, 191f, 195, 247, 303, 322, 352
pathway 92f, 333
inhibition of 184f
Cholesterol ester 303
transfer protein 243
activity of 82
Cholesterol guidelines 3, 35
comparison of 65
Cholesterol level 98, 132, 187
reduction in 45
Cholesterol lowering 153, 333, 429, 441, 716, 892f
action 398
agents 209
aggressive 430
effect 218
trials 229
Cholesterol synthesis 520
inhibitor 57, 205
Cholesterol transport
pathway 89
reverse 255
Cholesteryl acid 544
Cholesteryl ester transfer protein 544, 856
Cholestyramine 385, 749
Choroidal neovascularization 771
Chronic degenerative diseases, etiology of 138
Chronic inflammatory
conditions 19, 58, 110
disease 447
disorder 23, 37, 38, 110, 699
process 93, 670
states 780
Chronic kidney disease
moderate 57
progression of 561
severe 61, 67
Chronic obstructive pulmonary disease 140, 220, 419, 785, 786, 789
Chronic stress 137
situations 137
Chylomicron 83, 86, 169, 290, 337, 494, 725f, 780
remnants 86, 494
Chylomicronemia syndrome 290
Chyme 86
Cigarette smoking 317, 402, 494
Cimetidine 812
Ciprofloxacin 812
Circadian rhythm 135, 140
Cirrhosis 156, 158, 159
compensated 471
Clarithromycin 248, 350, 739, 812
Clear serenity trial 850
Clear tranquility trial 850
Clofibrate 385
Clonidine 713
Clopidogrel 652
Cochlea 208
Cochlea
hair cell 209
neuronal cells 210
Coenzyme 191
A 122, 172, 496, 506
Q, depletion of 192
Coenzyme Q10 192, 203, 216, 264, 357, 444, 711, 713
deficiency of 713
levels of 212
pharmacology of 713
potential role of 713
reduction of 153
role of 711, 712
Cognitive dysfunction 516
Cognitive function 297
impairment of 297
Cognitive impairment 62, 285
Cognitive symptoms 212
Cohort whereupon therapeutics require 340
Colchicine, low-dose 453
Colesevelam 749
Colestipol 749
Collagen 185
Colon cancer cells 718
Color Doppler 684
spectrum 679
technique 686
Common carotid artery 481, 584, 590, 658, 659
left 659
peak velocity in 598
Community health centers 63
Compactin 65, 122
Concomitant statin therapy 163
Confusion 85
assessment method 822
Congenital heart
defects 175
disease 251, 272
failure 405, 421, 711, 794
Connective tissue
disorders 83
growth factor 574
proteins 458
Constipation 749
Content and description 184
Contraception 38
Contraction strain values 647
Copenhagen 53
Cornea 774
Corneal arcus 81, 437
Corneal wound healing 768
Cornerstone therapy 447
CORONA trial 636
Coronary aneurysms 752
Coronary angiographic studies 613
Coronary angioplasty 141
Coronary arteriography 276
Coronary artery 371, 591
calcified 510
inflammation, left main 694
left 591f, 693
plaque rupture 329
stenoses 371
Coronary artery bypass graft 5, 27, 232, 238, 321, 547, 707
postoperative 238b
statin for postoperative 238
surgery 114, 118, 232, 238, 712
Coronary artery calcification 204, 612t
scoring 371
Coronary artery calcium 7, 21, 22, 36, 334, 393, 512, 513, 611, 611f, 615
measurement 110
score 271, 339, 581, 610
Coronary artery disease 12, 13, 25, 26, 50, 53, 85, 114, 119, 128, 132, 135, 156, 163, 194, 208, 232, 261, 266, 275, 279, 299, 309, 329, 332, 364, 367, 378, 402, 405, 415, 418, 431, 433, 436, 437, 447, 450, 457, 494, 505, 537, 599, 606, 639, 642, 654, 691, 757, 793, 795, 801, 857, 858, 860, 867, 869, 875, 882, 911
chronic 333
contraindications 801
high risk for 422
indications 801
malignant 187
management of 648
prevalence of 15
prevention of 66
Coronary atherosclerosis 328, 371, 553, 667
plaques 342
Coronary bypass surgery 282
Coronary calcification 610
Coronary calcium 372f
measuring 611
score 37, 57, 371, 372
statin effect on 371
Coronary circulation 329
Coronary death 67
reduction in 267
Coronary disease
eradication of 227
evidence of 183
Coronary heart disease 25, 36, 48, 74, 98, 102, 108, 115, 126, 137, 149, 165, 225, 261, 290, 303, 309, 328, 333, 347, 363, 368, 375, 392, 416, 459, 473, 505, 512, 542, 571, 582, 597, 691, 716, 752, 759, 827, 868, 879, 904
cause of 91
prevention of 224, 225
primary prevention of 303
risk of 149, 200, 437
Coronary intravascular ultrasound 875
Coronary octave 827, 827f
Coronary organic stenosis 335
Coronary plaques 275
Coronary revascularization 99, 123, 282, 368, 469, 474, 497
procedure 363
Coronary syndrome, chronic 117fc, 332334, 343, 855
Coronavirus disease crisis 815
Corpus cavernosum 152
Corticosteroids, doses of 169
Cortisol 135137
levels, lower 171
Cotrimoxazole 567
Cough 849
COVID-19 74, 238, 787789, 796, 815, 817, 818, 820
infection 197, 378, 796
pandemic 815
severe 74
statin in 74, 197
treatment of 185
use of statin in 817
C-reactive protein 19, 26, 32, 65, 66, 73, 76, 93, 97, 111, 147, 153, 164, 167, 178, 179, 191, 204, 218, 219, 236t, 239, 275, 280, 304, 311, 320, 323, 334, 344, 348, 368, 406, 429, 434, 466, 545, 810, 810f, 839
decreasing 520
high 856
high sensitivity 7, 21, 36, 37, 58, 77, 196, 206, 236, 272, 273, 340, 512, 801, 857, 878
role of 321f
Creatine kinase 124, 149, 163, 213, 214, 355, 357, 439, 738, 775, 812
Elevations of 66, 297, 498
Creatine phosphokinase 4, 308
Creatinine 99, 271
kinase 212
assessment of 213
Crystalline cholesterols 303
Curcuminoids 357
Cushing's disease 170
Cushing's syndrome 86, 169, 170
statin in 169
Cyclic guanosine monophosphate 149
formation of 152
Cyclophosphamide 567
Cyclosporine 66, 86, 163, 249, 567, 739, 812
CYFI P2 gene 245
CYP3A4
enzymes 263
isoenzymes 440
Cytochrome 567fc
P450 66, 127, 247, 248t, 349, 439, 739t
Cytokine 138, 178, 221, 452
expression, transcriptional activation for 770
imbalance 554f
storm 816, 818
Cytomegalovirus infection 875
Cytoskeletal organization 770
Cytosolic multiprotein 452
d
Dalcetrapib 255
Danazol 739
De novo lipogenesis 707
Dehydroepiandrosterone sulfates 206
Delirium 822
intensive care associated 820
Dementia 264, 268, 298, 394
incidence of 221
nonvascular 221
risk of 476
Density lipoprotein 86
cholesterol 65, 162, 317
Deoxyribonucleic acid 190, 909
Depression 268, 716, 717
treatment of 716
Dextran sulfate cellulose adsorption 16
Diabetes 18, 52, 57, 62, 82, 85, 86, 96, 111, 126, 140, 144, 150, 164, 174, 178, 184, 202, 263, 268, 269, 283, 290, 308, 317, 324, 361, 391, 405, 419, 473, 476, 481, 494, 509, 518, 527, 594, 716
affects 473
and statin use 219
control and complications trial 574
dangerous liaison of 476
diagnosed 285
dyslipidemia 545, 844
group, risk factors in 474t
hypertension 447
increased risk of 547
insulin-dependent type 1 96
lipid abnormalities, type 2 82
new-onset 66, 285, 471, 523
non-insulin-dependent 539
prevention, statin-induced 271, 274
statin in 474, 507, 531, 533, 537, 538
statin induced 263, 520
uncontrolled 85, 96
with obesity 542
Diabetes mellitus 6, 13, 27, 38, 61, 72, 89, 99, 102, 143, 149, 187, 219, 230, 237, 273, 289, 298, 312, 321, 334, 353, 364, 369, 400, 406, 447, 527, 534, 538, 542, 575, 622, 734, 757, 794, 828, 842, 844, 869, 888, 910
adults with 36, 109
causes 527
development of 66, 521, 845
incidence of 96, 225
new-onset 415, 439, 544, 739
prevalence of 509, 510f, 842
resolution 920
risk enhancers in 6b
risk of 249, 273, 285, 874
new-onset 350
statin-induced new-onset 272
type 1 31, 239, 369, 888
type 2 11, 21, 31, 67, 74, 79, 81, 94, 96, 109, 129, 152, 164, 257, 259, 263, 297, 320, 361, 369, 408, 509, 515, 517, 520, 527, 542, 554, 794, 874, 888
poorly controlled 290
Diabetes prevalence 509
estimate of 509
Diabetic cardiomyopathy 646f
Diabetic dyslipidemia 99, 167, 509, 515, 528, 542, 545, 547, 842
management of 97, 528, 843
mechanisms 842
pathogenesis of 544f
treatment of 529fc
Diabetic kidney 573
Diabetic macular edema, proliferative retinopathy of 772
Diabetic nephropathy 573, 576
lipid mediators in 574
management of 574
pathophysiology of 573
statin in 573
Diabetic patients 130
Diabetic population 229, 474
Diabetic retinopathy 769, 772
Diabetic stroke 474
Diacylglycerol 722
acyltransferase 252
O-acyltransferase 1 250
Dialysis 110
Diarrhea 308, 849
Diastolic dysfunction 441, 442, 510
Diazoxide 713
Diet 82, 754
Dietary carotenoids 719
Dietary cholesterol 228
levels of 228
role of 228
Dietary fat
absorption 309
to coronary risk 55
Dietary modification 747
types of 97
Dietary restriction 747
Dietary triacylglycerols 722
Diet-heart hypothesis 227
Dihomo-gamma-linolenic acid 727
Diltiazem 66, 567, 739, 812
Dimethylarginine dimethylaminohydrolase 180
Direct antioxidant mechanisms 809
Disability-adjusted life years 474
Diuretics 86
Dizziness 308, 849
Docosahexaenoic acid 11, 707, 741, 880
Doppler evaluation 681
Doppler study 627
Double filtration plasmapheresis 16
Downstream luminal pressure 494
Drug 741
classes 749
dose response of 811
interactions 739
Dry eye 767, 769
DTD1 gene 245
Dual antiplatelet
therapy 116
treatment 652
Duodenum 86
Dysbetalipoproteinemia 779
Dysfunctional endothelium 320
Dysglycemia 528
Dyslipidemia 10, 18, 25, 33fc, 40, 81, 85, 96, 118, 122, 135, 139, 139fc, 144, 150, 164, 165fc, 169, 170f, 174, 178, 200, 208, 220, 233, 247, 261, 289, 305, 321, 347, 361, 378, 397, 404, 409, 430, 452, 468, 473, 481, 493, 509, 528, 542, 561, 573, 654, 660, 686, 699, 701t, 705, 715, 752, 781, 827, 859, 866, 871, 882, 891, 900, 905, 919
and add-on therapy 364
causes of 85
clinical 289
control 509
development of 139, 752
diagnosis of 290
drug therapy 755, 909
during pregnancy, management of 175
etiopathogenesis of 262
genesis of 543
in pregnancy 174
inflicted stroke 833
management of 83, 102, 114, 164, 170, 201, 262, 282, 296, 369f, 459, 512, 530fc, 562, 563, 734, 781
guidelines for 297
pathogenesis of 543f
pathophysiological mechanism of 169
pathophysiology of 85, 86, 208, 918
plausible role of 379
postrenal transplant 565
prevalence of 378, 385
primary 81
resolution 920
risk factors of 81, 114
risk of 83
role of 562
screening for 752
spectrum of 527
statin in 208, 575
stress-induced 135
stress-induced 135, 138
therapy of 233, 848
treatment of 81, 158, 176, 187, 224, 402, 438, 562, 900
triggered atherosclerotic cardiovascular diseases 882
types of 85
Dyslipoproteinemia 528
Dyspepsia 253
Dyspnea 85
Dysrhythmia 921
E
Early statin treatment 592
Ebola virus disease 816
Echocardiography 594, 606, 627, 639
Echogenic plaque 659f
Edible oils 727
minor components of 722
Eicosapentaenoic acid 40, 99, 545, 707, 708, 741, 827, 880
Ejection fraction 441, 644, 654, 796
management 415
reduced 222
statin in 636
Elastic modulus 595
Elderly diabetics 515
Elderly hypertensives, cardiovascular risk in 404
Elective perioperative mortality 459
Elevated cholesterol, management of 539
Elevated triglycerides, treatment of 293fc
Embolism 116, 699
Emerging drugs 56
Emotions 140
Endarterectomy 599, 600
End-diastolic
velocity 598, 680, 684
volume 643
End-expiratory pressure ventilation, positive 820
Endocrine 194
disorders 81
system 135
Endogenous
lipoprotein pathway 86
pathways 86
Endothelial cell 132134, 178, 184, 660
activation 447
dysfunction 178, 842
function 817
injury 204
Endothelial damage 493
Endothelial dysfunction 147, 152, 153, 184, 194, 197f, 279, 317, 401, 406, 419, 447, 450, 473, 528, 684, 686, 816
and inflammation 537
reduction of 235
statin improve 147
Endothelial function 72, 132, 146, 147, 275, 303, 333, 335, 398
assessment of 196
effects on 301
enhancement of 420
improvement of 93
Endothelial injury 482
Endothelial lipase 340
Endothelial nitric oxide 93, 496
activity 640
synthase 133, 147, 153, 166, 180, 190, 191, 195, 196, 321, 344, 406, 465, 528, 701
Endothelial progenitor cells 93, 133, 406, 456
Endothelial surface 345
Endothelial-leukocyte interactions 93
Endothelin 147, 196, 318
Endothelin-1, expression of 772
Endothelium 194
dependent vasodilation 188
function of 184, 343
Endotoxin 812
lipoprotein hypothesis 421
Endovascular stent 459
End-systolic volume 643
Energetic fuels, mobilization of 135
Enterocytes 244
Enzymatic system 203
Enzyme 190, 262, 308, 330
guanylate cyclase 147
metabolizing 242
transporters 242
Eosinophilia, drug rash with 781
Eosinophils 786
Epicardial arteries 332
Epicardial coronary arteries 275
Epigastric approach 681f
Epinephrine 135137
Episcleritis 769
Epithelial cell injury 786
Erectile and gonadal functions 153
Erectile dysfunction 146, 147, 149, 150, 152, 683
color Doppler evaluation of 683
development of 152
pathophysiology of 147, 149f
pharmacotherapy of 149
statin 152, 153b, 154f
treatment of 149
Erectile endothelial functions 154
Erectile function 147, 152, 153f
male 152
Erectile hardness
grading of 684
score 684
Eruptive xanthomas 290, 780
Erythromycin 248, 350, 567, 716, 739, 812
Estimated glomerular filtration rate 46, 31, 37, 272, 284, 369, 392, 562, 794, 804, 888
Estrogen 135
deficiency 184
receptor 221
Ethnicity 7, 38
Ethyl eicosapentaenoic acid 292
Euthyroid person 162
Evinacumab 69, 250, 254, 352, 353, 368, 862, 863, 867, 868, 912
Evolocumab 10, 16, 27, 47, 351, 361, 363, 364, 497, 750, 839, 867, 873t, 875, 883
Excessive oxidation, role of 317
Exercise 83, 89, 200
role of 201, 202f
Exogenous lipoprotein pathway 86
External elastic membrane volume 277
Extracellular matrix deposition 184
Extracellular superoxide dismutase 192
Extrahepatic sites 128
Extraocular muscle 769
Eye
disease, age-related 771
vitrectomized 771
Ezetimibe 3, 10, 28, 30, 40, 46, 68, 77, 77t, 79, 93, 97, 167, 187, 215, 240, 282, 286, 291, 294, 339, 347, 351, 353, 368, 437, 438, 448, 451, 469, 475, 497, 529, 538, 544, 583, 608, 739, 749, 861, 862, 897f
administration 78
association 78t
combination 76
dosage of 79
effect of 451
on atherosclerosis, effects of 451
pharmacological characteristics of 76
plus simvastatin 368
role of 544
tolerability of 79
F
Familial chylomicronemia 290
syndrome 310
Familial dysbetalipoproteinemia 51, 290, 337
Familial dyslipidemia 290, 328330, 337, 367, 433, 436, 584
management 859
spectrum of 338
Familial heterozygous hypercholesterolemia 54
Familial homozygous hypercholesterolemia 54
Familial hypercholesterolemia 11, 1316, 31, 51, 57, 61, 67, 99, 114, 200, 237, 243, 266, 289, 300, 307, 324, 329, 330, 337, 352, 364, 369, 436, 512, 549, 749, 752, 757, 759, 840, 859, 861, 864, 874, 884, 888, 900
causes of 86f
cholesterol burden in 339f
diagnosis of 860
evidence of 513
genetics of 14, 859
heterogeneity of 15
management of 436, 757, 758
screening of 859
therapies for 750
treatment of 757
Familial hyperchylomicronemia 779
Familial hyperlipidemia 85, 174, 779t
Familial hypertriglyceridemia 67, 289, 290, 752, 779
Familial hypoalphalipoproteinemia 290
Familial lipoprotein lipase deficiency 779
Family meals 748
Farnesyl pyrophosphate 132, 204, 218, 221, 421, 456
Fasting plasma
glucose 525
triglycerides 553
Fat 54, 727, 728
and saturated fats 55
classification of 723, 723f
soluble vitamins 719
Fatal coronary
artery disease 273
thrombi 342
Fatal stroke, risk of 285
Fatigue 203, 420, 849
Fat-soluble
phytochemicals 719
vitamins 722
Fatty acid 40, 543, 751
metabolism of 257
profile 726t
synthesis 307
Fatty alcohols 722, 723
Fatty deposits 82
Fatty liver 158
Fatty streak 266, 271, 581
Femoral artery
B-mode ultrasound of 588
common 584
Fenofibrate 69, 98, 351, 166, 749
statin combination therapy 286
Fentanyl 812
Fibrates 98, 166, 215, 292, 294, 307, 497, 529, 741
actions of 292f
role of 452
Fibric acids 749
Fibrillation 708
Fibrinogen 179
Fibroatheroma 118
Fibroblast growth factor 133
Fibrofatty
atherosclerotic plaque 591f
plaque 277
Fibrosis 167, 786
stage 159
Fibrous cap 657
atheroma 276
tensile strength of 320
Fibrous core 672
Fibrous plaque 277
Fish oils 497
Flaccid 684
Flank approach 681f
Flavonoids 240
Flow-mediated dilatation 563
Fluconazole 567, 812
Fluorodeoxyglucose 693, 695, 700, 701
Fluvastatin 39, 44, 72, 105, 108, 123, 128, 157, 173, 185, 187, 236, 242, 261, 279, 318, 335, 375, 398, 405, 434, 459, 475, 520, 538, 562, 565, 567, 570, 759, 835
extended-release 759
Fly-buy renal angiography 505
Foam cell 275, 582
Focal segmental glomerulosclerosis 562
Follicle-stimulating hormone 206
Fourier trial 27
Framingham heart 473
Framingham offspring study 557
Framingham risk score 392, 584, 804
Fredrickson classification 289
modified 779t
Free cholesterol 751
Free fatty acid 82, 522, 523, 554, 554f, 722
Free radical
generation 726
role of 727
G
G protein-coupled chemokine receptor-7 701
Gallbladder stones 172
Gallstone 172
disease 172
prevalence of 172
formation 172
recurrence 172
Gamma interferon 320
Gamma-aminobutyric acid 717
Ganglionopathy 153
Gangrene 493, 494
Gastrointestinal side effects 292
Gastrointestinal symptoms 749
Gastrointestinal tract 167
GATM gene 245
Gebrochenes-Herz syndrome 378
Gemcabene 250, 253, 862, 864, 912
Gemfibrozil 386, 739, 749
Gender and cardiovascular risk 262
Gene
encoding, polymorphism in 242, 243
expression 525
silencing 249
polymorphism of 243
therapeutic agents 249
therapy 340, 750
Genetic confirmation, prevalence of 329
Genetic considerations 436
Genetic defect 338
Genetic disorders 200, 208, 255, 266
Genetic dyslipidemia, signs of 10
Genetic hyperlipidemias 54
Genetic predisposition 494
Genetic susceptibility factors 227
Genome, advances in 245
Genomic ribonucleic acid 816
Genotypic components 337
Geranyl pyrophosphate 218, 221, 222
Geranylgeranyl pyrophosphate 132, 196
Ghrelin 137
Glaucoma 765, 774
open angle 765
Global database analysis 915
Glomerular filtration rate 98, 130, 569, 573, 850, 912
Glucocorticoid 83, 85, 136, 169, 170f
therapy 174
Glucosamine 357
Glucose
fasting 273
homeostasis, statin on 149
intolerance 292, 522, 749
levels 919
tolerance, impaired 594
transporter 523
Glucuronosyltransferases 127
GLUL gene 245
Glutathione 190
peroxidase 190
reductase 190
Glutathione-S-transferase 190
Glycated hemoglobin 58, 439
Glycated lipoprotein 299
Glycation enhances 299
Glycemia 363
Glycemic control 97, 99, 141
Glycogen storage disease 89, 290
Glycoprotein synthesis 333
Goal-directed medical therapy 233
Goblet cell hyperplasia 786
suppression of 786
Gonadotropins 135
Gout 850
Graft versus host disease 768, 769
Grapefruit juice 186, 567, 739
Graves’ disease 163
Grayscale median 660
Growth hormone 169, 170
decreased 86
GSDME gene 245
Guanosine triphosphate 149, 638, 810
Guinea pig 209
H
Haloperidol 812
Haptoglobin 179
Harmacogenetics implementation consortium 245
Head and neck cancer 833, 834t
Headache 186, 749, 849
Health paradox 726
Healthy diets 56
Healthy human volunteers 310
Healthy nutrition 224
and statins 226
Healthy protein sources 3
Hearing loss 208, 209, 209t, 210
epidemiology 208
etiology of 208
in vitro 209
incidence of 208
noise-induced 209
pathophysiology of 208
progress of 209
sensorineural 208, 209
statin in 208
treatment 208
of sensorineural 209
Heart
and renal protection 75
protection 97, 539, 570, 599, 737
rate 707
Heart attack 539
risk for 179
Heart disease 18, 146, 261
chronic 181
prevention of 202f
Heart failure 67, 75, 104, 149, 163, 202, 218, 267, 283, 334, 378, 402, 405, 415, 418, 421, 431, 441, 442, 453, 547, 635, 654, 795, 802, 857, 919
acute 422
chronic 422, 654
device therapy in 441
history of 282
hospitalizations 218, 626
nonfatal 626
management of 418, 422, 442, 626
prevention 422fc
severe 470
statin in 67, 218, 413, 418, 420, 421t, 635, 636
with coronary artery disease 422
with preserved ejection fraction 443
without atherosclerosis 421
Heat shock proteins, control of 334
Helsinki heart study 742
Hematopoiesis 179
Hemeoxygenase 190, 809, 810
Hemodynamic shear stress 343
Hemoglobin, glycosylated 308
Hemorrhage
intracerebral 468
intracranial 471
intraplaque 481, 482, 672
preretinal 770
subarachnoid 822
vitreous 770
Hemorrhagic stroke 74, 104, 230, 258, 268, 285
high risk of 230
incidence of 104
increased risk of 350, 439, 739
Heparin mimetics 876
Hepatic cholesterol synthesis 65
Hepatic decompensation, prevention of 159
Hepatic dysfunction, severe 351
Hepatic exposure 242
Hepatic expression 759
Hepatic fibrosis 168
Hepatic hydroxymethylglutaryl coenzyme A 562
Hepatic lipase 244
Hepatic metabolism 439
Hepatic steatosis 159, 309
Hepatic stellate cell 220
Hepatic synthesis 363
Hepatic toxicity 298
Hepatic transaminases
assessment of 213
monitoring of 309
Hepatic venous pressure gradient 159, 220
Hepatitis
B, chronic 165
C, chronic 165
Hepatocellular carcinoma 168
Hepatocellular injury 157
Hepatocyte 179, 244
injury 156
Hepatotoxicity 158, 258, 285, 749
Heterozygotes 328, 338, 436
Heterozygous 14
familial hypercholesterolemia 10, 12, 14, 50, 85, 175, 251, 308, 312, 337, 661, 759, 849, 859, 862, 874, 878, 883, 885, 902, 907, 910912
High-density lipoprotein 18, 50, 52, 81, 85, 89, 110, 115, 164, 172, 174, 175, 201, 206, 227, 244, 267, 280, 289, 300, 311, 343, 468, 566, 574, 617, 683, 715, 724, 725, 767, 780, 801, 809, 816, 817, 891
cholesterol 6, 9, 13, 37, 51, 52, 52f, 77, 128, 167, 235, 238, 247, 254, 282, 293, 312, 324, 361, 405, 408, 438, 527, 547, 553, 566, 569, 583, 660, 733, 735, 752, 753, 820, 835, 860, 866, 872, 911, 919
High-efficiency particulate air 333
High-intensity statin 30, 49, 115, 157t, 271, 325, 344, 351, 374, 375t
plus ezetimibe 49
therapy 4t, 5, 20t, 27, 116, 127t, 274, 304, 409, 430, 471, 474, 570t, 614
High-intensity trials 858t
Histamine 785
Histidine decarboxylase 785
Home food 754
environment 748
Homozygotes 328, 436
prevalence of 337
Homozygous 329
familial
dyslipidemia 329
hypercholesterolemia 14, 50, 114, 175, 251, 308, 338, 340, 352f, 434, 759, 859, 862, 874, 885, 902, 910, 911
Hormonal changes, statin-induced 153
Hormone 136
production 257
replacement therapy 262
Hounsfield scale 887
Hounsfield units 611, 612
Human aortic endothelial cells 179
Human immunodeficiency virus 4, 36, 38, 19, 110, 512, 716, 739, 809
infection 23, 35, 38, 752
protease inhibitors 350, 739, 812
Human inflammation 235
Human monoclonal antibody 27, 352
Human organs, functioning of 91
Human umbilical vein endothelial cells 179
Hydralazine 713
Hydrochlorothiazide 408, 713
Hydrolysis 725
Hydrophilic statins 65, 67, 72, 258, 356, 475
except 259
Hydrophobicity 242
Hydroxy methylglutaryl coenzyme A 583
Hydroxy β-methylglutaryl-coenzyme A 133
Hydroxy-3-methylglutaryl 801
coenzyme 76, 758, 768
reductase 638, 770, 862
Hydroxychloroquine 524
Hydroxymethylglutaryl 820, 860
coenzyme 91, 97, 183, 434, 510
A 221, 235
reductase inhibitors 713
Hydroxytyrosol acid 727
Hypercholesteremia 143
Hypercholesterolemia 77, 78, 93, 128, 132, 175, 183, 184, 190, 195, 244, 273, 328, 329, 378, 379, 397, 399402, 406, 436, 581, 594, 683, 740, 750, 809, 911
family history of 329
high risk of primary 126
management of 76, 79, 133, 175
primary 7, 18, 23, 58, 166
severe 5, 36, 37, 40, 108, 742, 911
treatment of 333
Hyperchylomicronemia 779
Hypercortisolism, correction of 170
Hyperglycemia 82, 96, 292, 521, 574, 575, 780
chronic 527
fasting 291
Hyperhomocysteinemia 178, 184, 594
Hyperinsulinemia 137, 138
Hyperintense 672
Hyperkalemia 356
Hyperlipidemia 18, 51, 54, 81, 138, 158, 170, 176, 208, 209, 209t, 220, 230, 262, 290, 305, 317, 320, 335, 338, 379, 390, 419, 422, 564, 575, 684, 749t
causes of secondary 86b
classification of 50
control
primary prevention of 236
secondary prevention of 236
diagnosis of 162
familial combined 67, 289, 290, 337, 752
management 57, 238, 565
cornerstone of 56
primary 85
secondary 85
treatment of 56
Hypersensitivity 796
reaction 803
Hypertension 18, 38, 81, 93, 99, 126, 139, 140, 143, 150, 170f, 202, 282, 291, 308, 317, 321, 385, 388, 397, 400, 401, 401t, 418, 419, 473, 481494, 522, 542, 553, 581, 594, 622, 712, 717, 780, 833, 849, 920
absence of 391
classification of 402t
cumulative incidence of 403f
early-onset 404
elderly with 390
global burden of 397
increases 405
isolated systolic 399
management of 409
nonpharmacological therapy of 828
presence of 391
prevalence of 7, 385, 397, 398, 403f
resolution 920
role of 262
statin in 397
systemic 184, 638
treatment of 224, 405
types of 404
with cardiovascular diseases 404f
Hyperthyroidism 162
drug interactions in 163
lipids in 162
modification in 163
statin therapy in 163
treatment of 162
Hypertriglyceridemia 23, 82, 86, 126, 166, 215, 289291, 291t, 310, 707, 749, 753
causes of 86, 289, 290t
secondary 89b
clinical significance of 290
management 176
risk factors for 86
Hypertrophy 638
Hyperuricemia 850
Hypocholesterolemia 727
effect 128
Hypoglycemic agents 545
Hypointense 672
Hypolipidemic disorders, group of 338
Hypolipidemic drugs 175
Hypolipidemic therapy 322
Hypotensive action, mechanisms of 398
Hypothyroidism 81, 86, 174, 290, 834
radiation-induced 834
Hypoxia 699
I
Icosapent ethyl 250, 253, 352, 292, 450, 707, 878, 880
current therapeutic status of 880
role of 545
Idiopathic pulmonary fibrosis 788, 789
Idiosyncratic reactions 124
IGTB3 gene 245
Ileal bypass surgery 202
Immune
absorption 16
cell maturation 180
reactions 179
system 135
Immunomodulatory effects 65, 809, 810
Immunosuppressive drugs, effects of 233
Implantable cardiac devices 441
Implantable cardioverter defibrillator 418, 433, 441, 708
Inclisiran 41, 48, 69, 307, 308, 340, 352, 353, 363, 364, 368, 848, 862, 863, 875, 878, 880, 894, 897, 897f, 903t, 904, 907, 909
advantages of 907
dosage 875
drug trials 910t
effect of 48f
of action of 363f, 895f
pharmacodynamics of 875
phase-3 trials with 903t
recent trials of 900
safety of 895
side effects of 849b
therapeutic status of 880
therapy 891
use of 880
with statins 896
and effect 363
Indinavir 812
Infectious diseases, use of statins in 816
Inflammasome 452
Inflammation 56, 164, 167, 452, 493, 694, 700fc, 769
development of 146
effects on 544
lowering 111
role in 201
Inflammatory agent 524
Inflammatory cell 320, 320f, 785f
infiltration, decrease 180
number of 195
peribronchial infiltration of 787
perivascular infiltration of 787
Inflammatory cytokines 437, 453
reduce 93
Inflammatory disease 138, 657
Inflammatory eye disease, statin in 774
Inflammatory markers 178
statin on 73
Inflammatory mediators, secretion of 275
Inflammatory molecule, decrease in 345
Inflammatory processes 91
inhibition of 398
Inflammatory response, moderate 146
Inflammatory serum markers 810
Inflammatory states, acute 429
Inflammatory syndrome 809
Infrainguinal bypass surgery 305
Inhibit cancer-cell proliferation 716
Inhibiting monoclonal antibodies 749
Inhibitors
reductase 91, 183
types of 883
Initiating tissue inflammation 456
Insights 91
Insulin 81, 82, 86, 528
action, defects in 96
resistance 138, 139, 164, 225, 291, 439, 556, 919
role of 528f
secretion 716
sensitivity 83, 525
effects on 544
sensitizer 292
Intense lipid-lowering therapy, evidence for 144
Intensity hydrophilic statins 157
Intensity lipophilic statins 157
Intensity regimens, statin dose for 387t
Intensity rosuvastatin 304
Intensity statin therapy 19, 570
Intensive care unit 811, 820
delirium, statin in 822
Intensive cholesterol-lowering therapy 584
Intensive lipid-lowering therapy 334
Intensive rosuvastatin therapy 344
Intercellular adhesion molecule 195, 768, 775, 856
Interferon 342, 768
γ production 775
Interleukin 164, 170, 179, 276, 323, 450, 451, 768
Internal carotid artery
peak velocity in 598
right 482f
Interstitial lung disease 357, 359, 785
Intestinal cholesterol absorption 67
Intestinal microbiota 555
Intestine 459
Intima media thickness 408, 581
Intracellular calcium ions 378
Intracellular cholesterol 65
content 520
promotes 333
Intracellular tetrahydrobiopterin 191
Intraocular pressure, raised 765, 774
Invasive mechanical ventilation 821
Irbesartan 812
Ischemia 132, 465
amputation for 497
symptomatic 74
Ischemic cardiovascular disease 585
Ischemic cerebrovascular accidents, history of 102
Ischemic disease 539
Ischemic heart disease 51, 52, 147, 474, 553, 691, 801
risk factors for 257
Ischemic nephropathy, progressive 505
Ischemic stroke 98, 143, 321, 347, 368, 470, 483, 553, 842
fatal 98
non-fatal 98
reduce 74
Isoenzymes 349
Isoflavones 357
Isomerization 725
Isoniazide 567
Isoprenoid 105, 183
biological actions of 191f
molecules, production of 184
Isoprenylation, inhibition of 556
Isotretinoin 83
Isovolumic relaxation phase, strain rate during 627
Itraconazole 248, 739, 812
J
Joint xanthomas 85
Jupiter trial 26
K
Kawasaki disease 752
Ketoconazole 170, 248, 350, 567, 739, 812
interferes 170
Kidney
injury, contrast-induced 284
transplant 110, 576
Kidney disease 174, 219, 409, 562, 566
chronic 5, 10, 19, 31, 35, 58, 98, 110, 115, 123, 126, 145, 158, 219, 233, 249, 251, 259, 272, 282, 284, 290, 369, 392, 405, 419, 474, 518, 534, 566, 569, 622, 735, 788, 794, 804, 850, 869, 888, 910
progression of 561
Kidney function 398
adverse effects on 350, 439
impaired 488
progression of 284
L
Lacunar infarct 474
Lacunar strokes 465
Landmark trials and research 570
L-carnitine 203
Lecithin 722
cholesterol acyltransferase 50, 255
Left atrium strain 654
Left ventricular dysfunction 453
Left ventricular ejection fraction 67, 335, 441, 626, 635, 650, 708, 712
Left ventricular epicardium 643f
Left ventricular function 617, 639
Left ventricular hypertrophy 93, 232, 402, 408, 638, 639
and mass 639
statin in 640
Left ventricular mass 639
Lenticulostriate 465
Leptin, regulation of 555
Lescol renal transplantation, assessment of 565
Lesions, development of 179
Lethal ventricular arrhythmias 433
Leukoaraiosis 474
Leukocyte 93
adhesion 670
function 702
antigen 775
Lichen planus 780
Lidocaine 567
Lifestyle
interventions 54
management 10, 35
modification 12, 13, 97
therapy 22
therapies 20
Life-threatening arrhythmias 441
Limb 459
ischemia, critical 495, 497
loss 495
revascularization 497
Linolenic omega-3 728
Lipemia retinalis 290
Lipid 52, 722
accumulation 670
analyses 312t
apheresis 89, 368
association 324
buildup 699
core 672
effects on 438
goals 102
imbalance of 311
in myocardium, mechanisms of action of 629fc
low-density 683
mild elevations of 85
nephrotoxicity hypothesis 562
on myocardium, adverse effects of 378
oxidation 149, 452
pathways 87f
peroxidation 192
pool 614
statin effect on 73
targets 748
Lipid abnormalities 82, 561b, 779, 842
improve 429
Lipid disorders 50, 81
cutaneous manifestations of 779
management of 3, 5
screening for 754t
Lipid guidelines 57
current 61
Lipid management 57f
consensus in 56
statin for 158
treatment algorithm for 117fc
Lipid metabolism 86, 493, 527, 788, 816, 843
disorders of 779
Lipid parameters 524
evaluation of 10
Lipid profile 97, 130, 801
fasting 564
measurement of 3
Lipid-lowering 25, 26t, 61, 164, 398
agents 164, 166, 470, 839
arm 737
armamentarium 862t
drug 20, 39, 165, 176, 247, 286, 330, 353, 353t, 528
effect of 493, 556
efficacy 247
implementations of 61
medications 498
nutraceuticals 216
regimen 16
therapy 15, 28, 68f, 126, 127, 127f, 338, 469, 471, 496, 506, 576, 583, 691, 885
stable 16
targets in 30
treatment 267, 539
Lipid-modifying
agents 343
drugs 102, 733
therapy 69
Lipid-modulation 46
strategies 46
Lipidosis, direct 209
Lipid-rich core, fibrous cap of 275
Lipodystrophy 89
Lipogenesis 169
Lipolysis 169
Lipophilic statins 65, 128, 474, 520
Lipopolysaccharide 235
cholesterol, low-density 543
Lipoprotein 18, 37, 50, 53, 54, 57, 69, 86, 89, 162, 225, 247, 299301, 312, 330, 367, 438, 450, 451, 494, 494t, 512, 724, 735, 750, 753t, 839, 887
A 7, 12, 21, 67, 250
abnormalities 96
cholesterol, high density 542
classes 724f
concentration of 69
containing 247
triglycerides 493
effect on 734
inhibitor of 309
intermediate density 9, 561, 575, 724, 793
like metformin 545
lipase 69, 170, 174, 202, 244, 252, 340, 910
activity of 162, 201
metabolism 718
disorders of 859
modification 96
plasma levels of 448
types of 50t, 87f, 725f
Liver 212, 333, 544
adverse effects on 350, 439, 739
after cell injury 180
injury 145, 157, 160
steatosis 167
steatosis in 167
to spleen 159
transplantation 340, 751
Liver disease
active 803
cause of 164
chronic 158
Liver enzyme 106, 309, 355, 359
aspartate transaminase 285
asymptomatic 160
elevation of 124, 358, 850
Liver function
normal 157
test 124
Liver tests 158
abnormal 157
L-nitro arginine methyl ester 195
Local arterial stiffness, evaluation of 595
Local hemodynamics 275
Lomitapide 16, 69, 215, 250, 253, 308, 309, 340, 368, 862, 911
inhibits 16
Lopinavir 812
Losartan 812
Lovastatin 39, 44, 65, 72, 73, 105, 108, 123, 128, 157, 163, 170, 173, 185, 187, 229, 240, 242, 261, 262, 304, 375, 405, 434, 459, 475, 520, 529, 534, 538, 562, 567, 570, 717, 812
absorption of 128
Low physical activity 433
Low-cholesterol diet 209
Low-density lipoprotein 26, 45, 50, 54, 61, 81, 86, 87f, 91, 115, 122, 123, 158, 164, 170, 172, 175, 178, 194, 201, 202, 206, 227, 232, 238, 250, 254, 266, 275, 280, 292, 299, 311, 321, 333, 352, 362, 371, 378, 390, 406, 419, 456, 466, 549, 608, 617, 654, 667, 692, 699, 715, 723, 748, 767, 779, 859, 868, 903, 919
adaptor protein 328
apheresis 300, 340, 750, 864
atherogenic 595
drug therapy for elevated 754
lower 573
lowering, targets of 61
metabolism 88, 200
pathway of 201fc, 267fc
particles 164
receptor 87, 292, 300, 520, 861, 866, 820, 876, 883, 906
Low-density lipoprotein cholesterol 4, 10, 18, 31, 31f, 33, 69, 86, 102, 109, 127, 157, 162, 183, 200, 218, 225, 237, 251, 273, 289, 296, 308, 322, 347, 361, 365fc, 369, 369f, 385, 408, 415, 438, 450f, 486, 511, 512t, 547, 554, 583, 597, 626, 660, 691, 734, 753, 759, 780, 794, 804, 835, 855, 859, 866, 882, 900, 901, 914
levels of 14
lowering 108
metabolism of 757
reduction of 49t, 132, 793
Lower extremity ulceration 493
Lower limb 144
Low-fat
dairy products 3
poultry 3
Low-intensity 614
statin 30
therapy 4t, 20t, 127t, 570t
Low-medium intensity statin therapy 498
Low-serum cholesterol 635
Low-wall shear stress 486
Ltraconazole 350
Lumbar spine 220
Lumen 614
Lung
cancer 785
diseases, acute 788
disorder 789
Lung injury
acute 820
statin in
acute 820
ventilator-induced 821
statin-induced 788
ventilator induced 820, 821
Luteinizing hormone 206
Lymphocyte 320, 458, 583f, 786
function 768
antigen-1 785
migration of 583f
Lymphoid cells, proliferation of 810
Lysosomal acid lipase 50
Lysosomes 361
M
Macrolides 812
Macrophage 195, 257
colony-stimulating factor 342
migration of 684f
Macular degeneration, age-related 769, 771
Malondialdehyde 726
Mast cell activation 786
Matrix metallopeptidase 235
Matrix metalloproteinase 133, 317, 342, 406, 448, 457, 465, 486, 520, 700, 701, 767, 771
activity 493
tissue inhibitors of 772
Maximum aortic wall thickness 667
MDGA1 gene 245
Mechanical ventilation 821
Medical therapy 291
Medication interactions 65, 66
Meibomian gland disease 767
Membrane
cholesterol 105
domains, part of 174
stabilization 452
trafficking 770
Memory 65, 66, 140
Mendelian inherited diseases 338
Menopause 262, 263
Menstrual irregularities 204
Mental fitness 138
Mental stress 727
Messenger ribonucleic acid 883, 909
Meta-analysis 911t
Metabolic disorder 81, 402, 409, 573
Metabolic parameters 228
Metabolic syndrome 11, 13, 18, 20, 58, 67, 73, 86, 110, 146, 149, 169, 179, 209, 225, 239, 284, 290, 291, 406, 418, 555f, 556, 594, 622, 780, 828, 919
prevalence of 10
statin in 556
Metabolism 65, 201
abnormal 88
affecting drug efficacy 242
Metalloproteinase 133, 188, 276
tissue inhibitors of 457
Metformin 205, 207
Methyldopa 713
Methylglutaryl coenzyme A 39, 322
Methylprednisolone 252
Metronidazole 567, 812
Mevastatin 65, 122
Microalbuminuria 185, 219
Microembolization, reduction of 345
Microglia 465
Micronutrients 54
Microscopic hematuria 518
Microsomal triglyceride transfer protein 244, 250, 308, 911
inhibitor 911
Microvascular disease 332, 335
Microvascular dysfunction 379
Midazolam 812
Middle east respiratory syndrome 787
Mini gastric bypass 920
Minimal change disease 562
Mipomersen 16, 69, 215, 250, 308, 309, 368, 750, 862, 910
Mitochondria
dysfunction 149, 190
electron transfer 257
function 421
injury 494
intima 379
normal 190
oxidases 190
Mitogen-activated protein kinase 190, 192, 419
Mitotane 170
increases 170
Mitral annular calcification 622, 623f, 624
associations of 622
management of 623
Mitral inflow 632f
Mitral leaflets, anterior and 623f
Mitral stenosis, development of 622
M-mode echocardiography 627, 639
Moderate-intensity statin 30, 49, 157t, 304, 375t, 534,
therapy 4t, 20t, 103t, 127t, 237t, 434, 516, 545, 570t
Modulates apoptosis 809
Moens-Korteweg equation 594
Molecular switches 257
Monacolin
K 240
KA 715
Monascus purpureus 715, 717
Monoamine oxidase 717
inhibitors 716, 717
Monoclonal antibody 45, 69, 249, 351, 544, 861, 872, 874, 883
Monocyte 218
adhesion of 583f
chemoattractant protein 276, 321, 701, 856
chemotactic protein 178
migration of 486, 583f
Monogenic lipid disorders 338
Mononuclear cells 178, 218, 447
Mononuclear phagocytes 299
Monounsaturated fat 727
Monounsaturated fatty acids 724, 726
Mortality
causes of 261, 459
reduction in 233
risk for 179
Mucus hypersecretion 786
Multiorgan dysfunction syndrome 821
Multiple focal intense 697f
Multiple lacunar infarcts 465
Multivariate analysis 159
Muscle 65, 66
ache 66, 258
adverse effects on 439, 738
biopsy, indications for 357b
cell
energy production 333
functioning 203
complaints 203
cramps 258
damage markers, role of 357
disease, statin-associated 62
effects, statin-associated 358fc
enzyme 203, 212
elevation 263
inflammation 212
injury 355
necrosis 350
pain 268
strength 203
toxicity 105
weakness 258
Muscle symptoms 66, 517
clinical index, statin-associated 213t
statin-associated 4, 66, 74, 213, 258, 285, 355, 356, 356t, 358, 517, 628, 738
types of statin-associated 356t
Muscular pain 439
severe 350
Muscular symptoms
mild-to-moderate 213
pectrum of 355
survey of 213
Musculoskeletal
derangements 203
health 263
system 169
Myalgia 79, 215, 261, 350, 356, 439, 517, 549, 849
less 186
statin-associated 356
to rhabdomyolysis 285
Mycobacterium tuberculosis 787
MYD88 gene 74
Myeloma, multiple 290
Myeloperoxidases 190
Myocardial apoptosis 420
Myocardial damage, reduction of 344
Myocardial deformation 642
parameters 595
Myocardial dysfunction 537, 809
Myocardial function 654
Myocardial hypertrophy 638, 640
Myocardial infarction 9, 46, 67, 99, 103, 109, 110, 114, 143, 180, 224, 232, 235, 251, 279, 281, 304, 318, 321, 333, 375, 402, 408, 418, 421, 430, 442, 450, 483, 487, 547, 626, 646f, 712, 733, 757, 794, 855, 857, 858, 867, 887, 906, 910
acute 262, 300, 323, 342, 347, 553, 628, 702
first 393f
history of 361
nonfatal 99, 296, 391, 400, 498, 707
risk for 65, 452
thrombolysis in 321, 321f, 537
Myocardial injury 233
Myocardial ischemia 374
reduction 45, 430
Myocardial mechanics 595
Myocardial performance index 627
Myocardial perfusion 324, 349, 691
postprocedure 324
Myocardium, actions on 93
Myoglobinuria 350
Myopathy 79, 102, 105, 124, 163, 233, 242, 350, 421, 749, 796
risk factors for 124t, 214
statin-induced 105, 213, 214fc, 738
Myopericarditis 429
Myositis 212, 258, 298, 356
Myotoxicity 263
N
Nasopharyngitis 849, 850
Natriuretic peptide, B-type 335
Natural killer activity 810
Nausea 290
Necrotizing autoimmune myopathy, statin-induced 629
Nefazodone 739
Nelfinavir 812
Neoplasms, incidence of 258
Neovascularization 335, 699
Nephropathy 96
contrast-induced 488
Nephrotic dyslipidemia 561
Nephrotic syndrome 81, 86, 290, 561, 561b, 562t, 563, 563fc, 752
efficacy in 563
statin in 561
Neurological diseases 221
Neurological disorders, statin in 822
Neurological symptoms 212
Neuropathy 96, 528
leading, statin-induced 153
Neuropeptide Y 138
Neuropsychiatric effects 258
Neurovascular diseases 820
Neurysmal disease 452
Neutrophils 786
Newer lipid-lowering drugs, classification of 250t
Niacin 98, 215, 255, 292, 294, 529, 749
Nicotinamide 317
adenine dinucleotide phosphate 180, 190, 191, 196, 280, 406, 422, 458, 466, 639
oxidase 195
Nicotine 82
Nicotinic acid 749
Niemann-Pick C1-like protein 68
Niemann-Pick protein 127
Nitric oxide 92, 133, 147, 152, 153, 218, 235, 348, 374, 406, 420, 434, 487, 520, 628, 683, 727, 809, 810, 817
activation of 494
availability of 194
deficiency of 178
production 390
reduction in 300
restoring 481
synthase 133, 303, 422, 565, 856
Nitrogen species, reactive 727
No statin therapy 614
Noise 208
Nonalcoholic fatty liver disease 18, 85, 156, 159, 164, 165, 165fc, 166168, 220, 284
risk factors for 164f
treatment of 158, 160
Nonalcoholic steatohepatitis 156, 159, 164, 166, 220, 284, 912
cirrhosis 159
treatment in 158
Nonantiarrhythmic drugs 433
Noncardiac surgery 233, 429
Noncerebrovascular vessels 493
Noncommunicable diseases 208
Nondiabetes group, risk factors in 474t
Nonenzymatic antioxidants 190
Nonesterified fatty apolipoprotein 544
Nonfasting triglyceride levels 52
Nonfatal stroke 99, 398, 469
risk of 285
Non-high-density lipoprotein 50, 368
cholesterol 52, 52f, 53f, 53t, 307, 753, 839, 909
Noninvasive imaging techniques 667
Nonischemic cardiomyopathy 442, 654
Nonlipid 322
Nonmodifiable risk factors 81
Nonpharmacologic interventions 747
Non-ST elevation-acute coronary syndrome 322
Nonstatin
drugs 307
lipid-lowering drugs 215, 307, 308t
medications 4
therapy 529
trials 94
Nonstenotic atherosclerotic plaques 116
Non-ST-segment elevation myocardial infarction 342, 795
Nontraditional therapies 749
Nonvitamin K oral anticoagulants 58
Norepinephrine 135137, 184
synthesis 137
Novel emerging therapies 862
Novel therapeutic target 28
Noxious insults 178
Nuclear acids transcription 257
Nucleic acids 466, 884
locked 884
Nutraceuticals 357
Nutrition 224, 705, 722
Nutritional interventions 224
O
OAS1 gene 245
OAS3 gene 245
Obesity 18, 81, 82, 89, 111, 140, 289, 290, 320, 397, 404, 522, 542, 543f, 553, 594, 622, 716, 717, 752, 755, 780, 828, 918, 921
adipose tissue 542
and metabolic syndrome 919
management, pyramid for 918f
paradox 553, 555
phenomenon of 554
treatment of 224
Ocular inflammatory diseases 774, 775
Ocular surface inflammation 768
Odyssey outcome trial 27, 47
Oils, minor components of 728
Oleic acid 728
Omega-3 fatty acids 99, 167, 176, 292f, 294, 352, 452, 529, 707709, 741
lower triglyceride 707
polyunsaturated 292
supplementation 709
role of 708
Open label extension 885
Ophthalmopathy 769
Optic nerve 765
Optic neuropathy, progressive 765
Optimal lipid-lowering therapy 325
Optimal medical treatment 855
Oral contraceptives 83, 89, 262
Oral hypoglycemic agents 82
Orchestrates development 174
Organ dysfunction 811, 812
Organ effects 65, 66
Organ rejection 810
Organ transplantation 233
Organic anion transporter polypeptide 812
ORION
phase-3 pooled analysis 902
program 900, 908
ORION-1 trial 900
ORION-10 906
trial 902
ORION-11 906
trial 902
ORION-3 trial 902
ORION-4 trial 903, 907
ORION-5 trial 903
ORION-8 907
trial 904
ORION-9 907
trial 902
Oryzanol 727, 728
Osteoarthritis 553
Osteoblast 220
Osteoclastogenesis 220
Osteoporosis 220, 716, 717
Osteoprotegerin 221
Ototoxic drugs 208
Ovariectomy 220
Oxidation 725, 727
Oxidative phosphorylation 379
Oxidative stress, exercise-induced 726
Oxidized lipoprotein 299
Oxygen species, reactive 190, 280, 402, 420, 487, 573, 640, 727
P
Palmar xanthomas 290, 337
Pancreatic lipases 86
Pancreatitis 85, 89, 172, 290
acute 470
prevention of 176
Papaverine 684
Paracrine 194
Paraoxonase 816
Parasympathetic nervous system 135
Paresthesias 85
Parkinson's disease 146
Peak atrial systolic strain rate 627
Peak early diastolic
strain rate 627
velocity 627
Peak systolic
strain rate 627
velocities 598, 680, 684
Pediatric dyslipidemia
management of 748f
therapeutic of 747
Pemafibrate 69, 293, 352
Pemphigus 780
vulgaris 780
Penicillium citrinum 72, 405, 515, 733
Penile arteries, color Doppler of 683
Penile cavernosal tissue 686
Penile Doppler
study technique 684
ultrasound technique 685
Penile endothelial dysfunction 153, 154
Penile intracavernosal pressure 153
Penile neuronal reflexes 154
Peptide, glucagon-like 58
Percent atheroma volume 591, 614, 740, 802
Percent lipid volume index 591, 592
Percent plaque volume index 591, 592
Percutaneous coronary intervention 5, 38, 48, 114, 116, 117, 282, 323, 349, 547, 795, 802, 857, 884, 887
Percutaneous intervention 887
Percutaneous transluminal coronary angioplasty 232
Perfusion 700fc
Peri-interventional stroke rate 487
Peripheral artery 597
disease 27, 50, 98, 102, 114, 126, 143, 249, 279, 283, 303, 321, 385, 457, 459, 473, 499t, 505, 537, 597, 598, 735, 842, 884, 887, 910
ischemia in 495f
treatment of 499t
Peripheral atherosclerotic disease 497
Peripheral edema 253
Peripheral neuropathy 518
Peripheral vascular disease 5, 135, 402, 493, 910
symptomatic 470
Peripheral vascular intervention 493, 498
Periprocedural infarction 225
Peroxiredoxins 190
Peroxisome proliferator-activated receptor 250, 741, 856
Peroxynitrite 190
Persistent hyperglycemia 573
Persistent hypertension 402
Pharmacogenomic genome 245
Pharmacokinetic genes 242
Phenolic acid 727
Phenotypic components 337
Phentolamine 684
Phenylpiperazine antidepressant 163
Phenytoin 567
Phosphatides 722
Phosphodiesterase 149
Phosphoinositide 133, 220, 221
Phospholipid 257, 493, 561
Physiological testosterone 153
Phytosterol 715, 717719, 723
absorption of 718
biological activities of 718
drug interaction 719
metabolism of 718
nutrient interaction 719
safety of 719
sources of 718
types of 717
Phytosterolemia 719
Pigment stones 172
Pitavastatin 39, 44, 56, 66, 72, 73, 108, 123, 126, 157, 158, 186, 187, 236, 247, 261, 356, 375, 405, 419, 434, 438, 459, 475, 476, 520, 529, 534, 538, 570, 584
Placebo 430
Planar xanthomas 780
Plant
extract 357
sterols 727
Plaque 481, 482f, 614, 684f
area 481, 658
atheroma 118
calcified 277
characterization 671
components 672t
disruption of 318
fibrofatty volume of 591, 592
formation 834f
grading consensus 658t
high-risk 613
length of 482f
low attenuation 450
mixed 598f
neovascularization 481
paradox 610
passivation 342
concept of 342
progression 321f, 699
regression 324
statin-induced 699
rupture 343, 493
score 658
stabilization 345, 885, 887t
stable 484
structure 485
thickness 658
visualization of 481
volume 452, 591, 673
vulnerability 345, 661
Plasma 14, 69
cholesterol 119, 188, 334
elevation of 81
glucose 716
lipids 556, 753t
effects on 188
lipoproteins 333
apheresis 300
low-density lipoprotein cholesterol 891
protein binding 349
protein-A, pregnancy-associated 323
Plasminogen
activator inhibitor 164
protease 299
Platelet 93, 583f
actions on 93
aggregation 335, 528
derived growth factor 276
specific fibrinogen receptor 245
Pleiotropic effect 132, 275, 322, 450, 456, 468, 515
mechanisms leading to 93
of statins, mechanism of 422fc
statin for 379
Pneumonia
community-acquired 785, 821
statin in ventilator-associated 812
Podocyte injury 564
Policosanol 240, 357
Polyclonal gammopathy 89
Polycystic ovarian syndrome 174, 204, 205f
Polygenic dyslipidemias 755
Polygenic hypercholesterolemia, severe 436
Polymeric compounds 224
Polymerization 725
Polymorphism 242
Polyphenols 240, 357
Polyunsaturated fat 727
Polyunsaturated fatty acid 12, 240, 292, 293, 707, 724, 726
Polyunsaturated lipids 724
Polyvascular disease 28, 48, 143, 324, 367, 369, 537
pathophysiology of 144
statin in 143
Posaconazole 248, 350, 739
Postablation 431
Postcardioversion 431
Postcoronary artery bypass grafting 5, 374
Postindex acute coronary syndrome 324
Postmyocardial infarction 5
Post-pacemaker implantation 436
Postprandial lipoprotein metabolism 82
Postrenal transplant, statin in 565
Post-transplantation dyslipidemia, management of 566fc
Potential antifibrinolytic effects 67
Potential anti-inflammatory effects 785f
Pravastatin 26, 39, 44, 45, 72, 73, 74, 104, 105, 108, 123, 128, 144, 157, 173, 180, 181, 185187, 202, 219, 236, 242, 261, 262, 279, 281, 285, 318, 330, 334, 343, 356, 375, 398, 399, 405, 434, 459, 475, 476, 520, 525, 529, 534, 538, 562, 563, 570, 591, 737, 835, 858
developments of 72
group 296
high-dose 158
in ischemic disease 322, 583
treatment 399
Prednisone 86, 89
Pregnancy 174, 803
and cardiovascular risk 263
category X 803
disorders of 263
Premature atherosclerosis 900
Preocclusion brachial artery 197f
Preproendothelin gene 133
Proatherogenic triglyceride 289
Progesterone 205
Proinflammatory cytokine 218, 235, 448, 810
Proinflammatory mediators 809
Proinflammatory transcription factors 810
Proliferative vitreoretinal disease 770
Proliferative vitreoretinopathy 770
Proliferative vitreous disease 770
Proprotein convertase subtilisin/kexin 9 6, 12, 22, 25, 30, 32, 33, 35, 39, 49, 68, 98, 115, 176, 215, 250, 251, 266, 292f, 328, 351, 364, 448, 450, 561, 748, 839, 861, 866, 868, 871, 875, 887, 891, 905, 906
biology of 843
gene 249
indications of 49b
monoclonal antibodies 905
protein, drugs targeting 866t
vaccine 48
Proprotein convertase subtilisin/kexin 9 inhibitor 4, 40, 4749, 68, 98, 117, 240, 293, 300, 339, 351, 361, 362t, 364, 438, 497, 544, 583, 701, 735, 740, 839, 842844, 861, 868, 868t, 875, 876, 882, 887, 888, 909, 910t, 914
dosing regimens of 867t
effects of 867, 885t887t
pharmacokinetics of 872
pharmacology of 867
plus intensity statin 49
resistance 875
statin and 286
therapy 866, 871
use of 868
with statins 361
Prostacyclin 147, 178
Prostaglandins 684
Prostate 718
cancer 269
Prostatic hyperplasia, benign 718
Protease inhibitors 86, 716
Protein 221
anchoring 257
kinase C 147, 178
activation of 573
kinase, activated 170
transfers lipids 911
Proteinuria 220, 284, 439
statin 219
Prothrombotic activity 53
Prothrombotic milieu 343
Prothrombotic state 919
Provitamin A 727
Proximal aortopathy 457
P-selectin expression 195
Psoriasis 19, 780
Pulmonary arteries 786
Pulmonary bifurcation, level of 668f
Pulmonary drug toxicity 788
Pulmonary hypertension 785, 786, 789
Pulse wave velocity 581, 594
measurement 595
R
Ramipril 652
Randomized controlled trial 26, 45, 73, 219, 356, 375, 549, 563, 565, 570, 734, 774, 794, 795, 811, 820, 861
Ranitidine 567, 812
Ranolazine 66, 739
Rapamycin, mammalian target of 565
Raynaud's phenomena 149
Reaction
adverse 186
injection site 301, 849
Red yeast rice 357, 715, 716, 719
clinical uses of 716b
role of 715
safety and efficacy of 716
Regeneron 254
Regular aerobic exercise 201
Remnant removal disease 779
Renal artery 680f
stenosis 505, 506, 679, 680
atherosclerotic 505, 506
bilateral 505
Renal complication 458
Renal disease 50, 81, 218, 398
end stage 569, 857
prevention of 398
progressive 398
Renal dysfunction 191, 232, 820
Renal failure 229, 402, 802, 812
chronic 89
Renal function 357, 359, 398
adverse effects on 739
improved 488
Renal insufficiency 431
Renal replacement therapy 562
Renal toxicity 259
Renin-angiotensin aldosterone system 399, 418, 679, 787
Renin-angiotensin system 430, 573
activity 430
Reno-aortic ratio 681
Renorenal ratio 680
Renovascular disease 677, 679
Doppler in 679
Renovascular hypertension 505, 679
development of 679
management of 505
statin in 679
Reservoir 647
Residual atherogenic dyslipidemia 866
Residual inflammatory risk 58
Resistant plaque burden 340
Respiratory diseases
asthma 220
syndrome, acute 787, 812, 815, 820
Respiratory failure, acute 378
Respiratory syndrome coronavirus, severe acute 815
Rest ischemia 496
Rest pain 493
Restoring endothelial function 335
Resveratrol 357
Retinal disease 50
Retinal pathologies 774
Retinal vascular diseases 772
Retinoids 83
Retinol 719
Retinopathy 96, 528
Rhabdomyolysis 102, 124, 158, 214, 233, 258, 356, 517, 738
high incidence of 124
Rheumatic fever, history of 418
Rheumatic heart disease 76
Rheumatoid arthritis 19, 83
juvenile 752
Rho-kinase pathways 178
Rhythm control 429
Richmond agitation sedation scale 822
Rifampicine 567
Rifampin 812
Right carotid
artery 598f
bifurcation 482
bulb 598f
Risperidone 812
Ritonavir 812
Rival statins 126
Rosuvastatin 39, 44, 56, 66, 67, 7274, 7679, 93, 102, 105, 108, 116, 123, 128130, 157, 166f, 186, 187, 191, 202, 206t, 207, 215, 236, 238, 242, 247, 261, 262, 267, 330, 356, 375, 398, 405, 434, 438, 459, 475, 476, 520, 525, 529, 538, 563, 570, 608, 801, 802, 812, 835
combination therapy of 78
current place of 76, 79
dosage of 79, 358
effect of 801
high doses of 130
lipid effects of 78
monotherapy 77, 79
effect of 220
pharmacological characteristics of 76
potency of 128
therapy, effect of 371
tolerability of 79
treatment 128, 130
uptitration 78
use of 129
Roux-en-Y gastric bypass 918, 920
S
Safety during treatment, monitoring of 11
Saroglitazar 167, 292
effect of 167f
Saturated fat 82, 723, 727
Saturated fatty acid 726
absorption of 722
Scandinavian simvastatin survival study 25, 737
Scavenger cell receptor 185
Sclerosis
acute lateral 146
multiple 146
Sedentary
behaviors 748
lifestyle 146
Selenoprotein hypothesis 421
Selumetinib 192
Sepsis 239, 809, 810f, 821
lipemia of 809
pathophysiology of 809
prevention of 820
statin in 809, 812
treatment of 820
Septal mitral annulus tissue Doppler 632f
Sequential organ failure assessment 374, 811
Serial intravascular ultrasound 740
Serum
alanine aminotransferase 220
aminotransferase 159
amyloid A 179
creatine kinase 245, 258
high 486
nitric oxide 153f
transaminases 803
triglyceride levels 83
Serum cholesterol 18, 65, 88, 635
levels 25, 194, 397
lowering of 91
management of 41
reduced 210
Sesamin 727
Sesamolin 727
Severe acute respiratory syndrome 816
coronavirus 2 197, 787, 815, 816
Sexual dysfunctions 150
incidence of 146
Shock, cardiogenic 378
Sick fat 918
Sildenafil 153f
Silent strokes 474
Simvastatin 25, 27, 39, 44, 56, 65, 7274, 93, 104, 105, 108, 123, 126, 128, 157, 163, 170, 173, 185, 187, 191, 202, 205, 207, 214, 236, 242, 261, 262, 269, 368, 375, 398400, 405, 434, 459, 474476, 520, 525, 529, 534, 538, 562, 563, 567, 570, 584, 608, 812, 835, 858
attenuates proinflammatory cytokine release 235
effect of 220, 693f
high-dose 245
monotherapy group 27
received 98
survival study 648
Single-gene disorders 328
Single-nucleotide polymorphisms 58, 338
Sitosterol 723
Sitosterolemia 244, 719, 740
Sleep 747, 754
Sleeve gastrectomy 920
Small body frame 233
Small interfering ribonucleic acid 250, 352, 905
molecules 884
oligonucleotides 905
Small intestine 93
Small vessel ischemia 357
Smoking 18, 81, 82, 99, 135, 141, 146, 178, 184, 405, 433, 447, 473, 481
cessation 495
current 282
Smooth muscle
contraction 194
dysfunction 56
hyperplasia 184
hypertrophy 786
Smooth muscle cell 72, 93, 133, 201, 267, 276, 348, 430, 582f, 871
apoptosis 699
migration 684f
decrease of 188
proliferation 185
Sodium
fluoride 700
glucose cotransporter-2 574
nitrite 153f
Soft plaque 277
Spinal cord ischemia 458
Spiral ganglion in vitro 210
Spontaneous dissection 116
Spotty calcifications 277
Stable angina 282
pectoris 185, 920
Stable atherosclerotic cardiovascular disease 44
Stanols 717
Staphylococcus aureus 767
Statin 39, 45, 53, 56, 67, 73, 75, 91, 99, 108, 116, 127, 133f, 138, 147, 156, 165, 178, 186, 200, 232, 239, 247, 257, 266, 271, 284, 291, 296, 317, 322, 332, 338, 351, 367, 387, 399, 405, 441, 469, 484, 498, 528, 540, 543, 562, 571, 588, 597, 617, 626, 642, 648, 660, 686, 707, 749, 758, 767, 785, 787, 804, 810, 816, 827, 860, 892f
absorption 128
act 65
actions of 134, 159f, 234
advances in 367, 441, 515
adverse effects of 111, 212, 213b, 269, 297, 394, 738
after renal transplant 565
after renovascular intervention 505
angiogenesis by 196
anti-inflammatory effects 179
associated muscle symptoms
clinical diagnosis of 356b
mechanism of 355
beneficial effects of 448fc, 553
block production 421
cardiovascular benefits of 529
categorization of 44t
class of 66, 520
classification of 529t
clinical
dose of 213
trials of 109t
use of 162, 524
combination 286
therapies 57
comparative efficacy of 262t
contraindications to 239b
controversy 227, 228
development of 202, 239, 267
discontinuation syndrome 45
discovery of 72, 132
dose for 67, 102, 273, 363, 459, 759t
drug interactions with 237
effect of 93, 114, 179t, 185b, 218, 219, 243, 299, 303, 304, 322, 324, 356, 398, 434, 438, 486, 496, 670, 672, 677
low-dose 133
efficacy of 72, 130, 347, 474
elderly and 67
eligibility criteria 272t
era 46
fibrinolytic effect of 196
genetic influences on 244
guidelines for 66, 391
high potency 259
high-dose 56, 102, 106, 811
high-intensity trials on 855
immunomodulatory effects of 810
indications of 248
influence of 399
inhibit 201, 468, 628
intensity of 123t
guideline-directed 239
interactions of 439
intervention 266
landmark trials on 737t
legacy effect of 111
less 281
lipid therapy beyond 914
live longer with 183
longer-acting 123
low intensity 157t, 375t
low-dose 102, 239, 811
matter, types of 400
mechanism of action of 65, 127, 205f, 348t, 897f
metabolism 127, 163, 440
moderate dose of 15, 334
monotherapy, use of 409
mortality benefits of 229
myalgia clinical index score 213
pharmacokinetic 123t, 127, 156, 242
properties of 157t
pharmacology 247
pleiotropic
actions of 303b
benefits of 406f
effect of 91, 92f, 195, 219t, 235, 235f, 333, 487fc, 544
mechanism of 330
properties of 630fc
plus ezetimibe 369
potential
effects of 768f
harm of 421
pleiotropic mechanisms of 809
therapeutic role of 785
pretreatment 487
primary prevention 274, 297
properties of 186t
protective role of 576
recent trials on 856
regimen 376
response, pharmacogenomics of 242
role of 170, 191f, 201, 204, 204fc, 267, 279, 317, 318, 329, 332335, 395, 418, 420, 447, 547, 555, 569, 570, 583, 607, 684, 765, 789t, 815
safety of 130, 157, 158, 249, 285, 738
high-dose 105
serum concentrations of 285
side effects of 62, 65, 74, 263, 264, 544
story 228
structure of 65
switching 802
symptoms 149, 628
target 458
tolerability 529
toxicity 239
trials of 348t
types of 351t, 570
ultimate 238
underutilization of 144
physician-induced 357, 359
usage 297, 511
use of 149, 259, 379, 385, 387, 391, 429431, 533, 547, 584, 686
variable properties of 72
Statin and
angiogenesis 132
aortic atherosclerosis 667
arrhythmias 434
arterial stiffness 595
asthma 786
atrial fibrillation 376
bronchiectasis 787
brown adipose tissue 556
cancer 62
cardiovascular events 129
carotid artery
disease 479
intima-media thickness 660
plaque volume 661
plaque vulnerability 661
revascularization 483
stenosis 660
cerebrovascular disease 304
chronic obstructive pulmonary disease 786
cognitive impairment 62
cornea 767
coronary artery disease 315, 648
COVID-19 787
endothelial function 195
erectile dysfunction 152
eyes 763
ezetimibe 286
fibrates 286
gallstones disorder 172
gut microflora 555
effect of 554f
heart failure 442
hepatocellular carcinoma 159
hypertension 383
hyperthyroidism 162
idiopathic pulmonary fibrosis 788
incident diabetes risk 540
inflammatory markers 178
kidney 559
lacunar strokes 466
lipid lowering 237
liver
disease 358
enzymes 106
low-density lipoprotein cholesterol control 114
lung infections 787
muscle symptoms 62
new-onset diabetes 62
nonalcoholic steatohepatitis 156
obesity 551
obstructive airway disease 786
ocular surface 767
peripheral vascular disease 305
placebo 372
plaque 371
vulnerability 483
pleiotropic actions 617
pleiotropy 415
proteinuria 220
pulmonary
disorders 785
hypertension 786
restrictive lung diseases 788
retinal disease 770
sepsis 821
in intensive care unit 239
sexual dysfunction 146
skin 777
stroke 62
tuberculosis 787
yoga 827f
Statin in
atherosclerosis, mechanisms of action of 275
diabetes, indications of starting 538
heart failure
effects of 119
role of 418, 422
hyperthyroidism, role of 162
metabolic syndrome, effects of 555f
obesity, role of 553
plaque
passivation, role of 343
regression, role of 700fc
primary prevention 62, 279
secondary prevention 62, 282, 282fc
sepsis, role of 810
stroke prevention, mechanisms of 465
Statin intolerance 130, 212, 240, 240t, 249, 258t, 352, 355, 355b, 358fc, 540, 879, 885
drug management in 358f
evaluation of 213
identify 212
management of 214, 358
prevalence of 240
risk of 213, 213b
Statin lower
plasma 127
testosterone 150
Statin on
angiogenesis, effects of 132
bone, beneficial effects of 221fc
carotid artery atherosclerosis, effect of 590t
coronary artery atherosclerosis, effect of 592t
erectile function, beneficial effects of 152fc
exercise, adverse effects of 203
femoral artery atherosclerosis, effect of 590t
inflammation, effects of 185
lipid profile, effects of 130
liver histology, effects of 165
plaque stability, effects of 185
smooth muscles, effects of 185
vasomotor function, effects of 184
Statin stimulate peroxisome 180
proliferator 180f
Statin therapy 4, 45t, 58t, 76, 93, 94, 119, 132, 135, 180, 185, 190, 200, 218, 232, 238, 245, 266, 268, 269, 271, 274, 279, 281, 283, 286, 297, 300, 303, 305, 322, 330, 334, 344, 345, 393f, 443, 449t, 457, 471, 475, 475t, 483, 487, 496, 498, 538, 553, 563fc, 584, 595, 597, 599, 600, 613, 626, 633, 657, 679, 683, 758, 843, 866, 878
advances in 67, 247, 320, 328, 351, 374, 385, 390, 429, 433, 436, 456, 465, 468, 473, 481, 486, 493, 496, 527, 542, 547
adverse effects of 471
and osteoporosis 264
before and after 627
benefit of 124
chronic 811
class of 322
classification of 405t
clinical evidence of 343
continuation of 811
controversies of 626
discontinuation of 212
dosage for 104
dual goals for 236
effect of 203, 269, 458, 459, 484f, 562t
enthusiasm for 230
gender disparity in 261
high-dose 103t, 214, 343, 376, 430
initiation of 322
intensity of 47
long-term 7, 629fc
monitoring of 237
nuances of 44
preoperative 374
problems of 296
promise of 833
role of 506, 597, 606, 622, 624
safety of 345
side effects after 630fc
unmet needs of 447, 448
Statin treatment 158, 300, 359, 394, 439, 488
effect of 339f
safety and efficacy of long-term 157
Statin trials 248f, 268, 539t
meta-analysis of 279
primary prevention 394t
Statin use
contraindications of 803
current guidelines for 803
Statin utilization 239
controversy over 259
wider 257
Steatosis 156, 159, 167
ST-elevation myocardial infarction 116, 347, 802
Stenosis 598, 679, 680f, 681f
distal to 679
end-diastolic velocity in 598
progression of 608
Steroid 85
biosynthesis inhibitors 171
hormones 86, 236
resistant nephrotic syndrome 561
Sterols 717, 722, 723
Stigmasterol 723
Storvastatin 242
Strain
circumferential 595, 645f, 646f
high 277
imaging 277, 627
longitudinal 645f, 646f
three-dimensional 643
Stress 135, 139fc
acute 136
cardiomyopathy 378
circumferential 343
diastolic 415
management of 136fc, 138
myocardial perfusion 692f
oxidative 56, 164, 190, 191, 317, 398, 405, 406, 434, 447, 494, 528, 771
proteins 334
psychological 137
role of 138
Stroke 6668, 81, 91, 99, 135, 137, 232, 269, 282, 284, 299, 347, 402, 457, 458, 465, 474, 481, 518, 794
fatal 283
mouse model of 465
nonfatal 283
pathogenesis of 833
prevention 45, 488, 599
statin in 468
primary prevention 468
rates, effect on 488
recurrent 469
risk for 179, 473, 473t
small 466
statin in 474, 475
acute 470
subtype 466
with diabetes 473, 476
ST-segment elevation myocardial infarction 304, 323, 328, 342
Subclinical cardiovascular disease 149
Subtilisin 32
Sudden cardiac
arrest 433
death 433, 498
Sugar 55
Sulfamethoxazole 812
Superoxide dismutase 190
Surgery, types of 920
Switching therapy 214
Sympathetic nervous system 135
Symptomatic gallstone disease 172
Synthetic statins 72, 122
Systematic coronary risk
estimation 388
evaluation 736
Systemic inflammation 379
Systemic inflammatory response syndrome 810
Systemic lupus erythematosus 89, 290, 752
Systolic blood pressure, high 76
Systolic dysfunction 441
Systolic strain, regional longitudinal 620, 628
Systolic velocity, high 680f
T
T cells, regulatory 179
Tacrolimus 567
Takotsubo cardiomyopathy 378
Takotsubo syndrome, statin therapy in 378
Tamoxifen 83, 89
Telithromycin 248, 350, 739
Tendinous xanthomas 780
Tendon
rupture 357, 359, 518, 850
xanthoma 329, 437
Teratogenicity 207
risk of 176
Terpenoid synthesis 257
Testicular atrophy 153
Testosterone 86, 135, 205, 206
production, inhibition of 153
low 357, 359
Tetrahydrobiopterin 180
T-helper cell 768, 810
Therapeutic modalities 20
Therapeutic plasma 176
Thiazide 83
diuretics 89
Thiazolidinediones 82
Thin-cap
atheromatic plaque 660
fibroatheroma 276
Thiobarbituric acid reactive substances 726
Thioredoxin 190
Thoracic aorta 672f
aneurysms 456, 457
descending 447, 448
Three-dimensional
plaque quantification 659
speckle tracking echocardiography 642
Thromboembolic strokes 484
Thrombogenicity 72
Thrombosis 81
Thrombotic complications 311
Thrombotic stroke 468
Thromboxane 93
Thrombus formation 328
Thyroid 135
hormone 834
muscle disease 163
profile 291
Thyrotoxic myopathy 163
Tissue
echogenicity 277
plasminogen activator 196
T-lymphocytes 93, 195, 456
types of 343
Tocilizumab 815
Tocopherols 727, 728
Tocotrienols 727, 728
Torasemide 567
Torcetrapib 255
Total atheroma volume 128
Total cardiovascular disease 31f
Total cholesterol 26, 174, 175, 206, 272, 311, 312, 369, 408, 547, 561, 565, 660, 752, 753, 835, 849, 878, 888
higher 204
Toxicity 74
Trans fats 55
Trans fatty acids 55, 723
Transaminases, increase in 518
Transesophageal echocardiography 447, 588, 670
Transesophageal ultrasound 667
Transforming growth factor-β 221
Transient ischemic attack 282, 305, 333, 420, 483, 599, 794, 842
Translocator protein 695, 700
Transplant vasculopathy 233
Transthoracic echocardiogram 588, 654
Triacylglycerols 722
Triglyceride 12, 32, 50, 52, 52f, 54, 57, 62, 77, 81, 85, 86, 137, 162, 174, 175f, 206, 244, 247, 250, 254, 290, 293, 294, 312, 408, 433, 438, 450, 547, 456, 566, 716, 724, 734, 752, 753, 835, 883, 920
and fatty acids, metabolism of 88f
concentration 83
drug therapy for elevated 755
elevation 294, 337, 919
enriched lipoprotein 300
hydrolysis of 69
reduction
pharmacological agents on 294
strategies 289
rich lipoprotein 32, 82, 289, 351, 750
risk 58
role of 452
serum elevations of 919
treatment of high 707
Trimethylamine oxide 828
Triphosphate-citrate lyase 892
Tuberculosis 220, 694, 787, 789
Tuberoeruptive xanthomas 780
Tuberous xanthomas 81, 780
Tumor necrosis factor 276, 280, 334, 342, 456, 556, 767, 772, 809
U
Ubiquinone 444, 522
hypothesis 421
Unsaturated fatty acids 724
Unstable angina 48, 66, 99, 103, 225, 235, 342, 707, 795, 910
pectoris 281
Unstable plaques 474
Uric acid 292
Urinary tract infection 850
Urine
dopamine in 137
protein 220
Uveitis 769, 774
statin in 774
V
Valve surgery 232
Valvular stenosis 456
Vascular atherosclerosis 689, 691, 699, 701t
Vascular cell
adhesion molecule 1 674
phenotype of 184
Vascular disease 486
history of 348
Vascular endothelial
cells 299
dysfunction 401
function 712
growth factor 132134, 221, 379, 573, 771
Vascular endothelium 97
Vascular end-stage disease, prevention of 398
Vascular events, incidence of 98
Vascular homeostasis 843
Vascular smooth muscle cell 93, 194, 276, 447, 450, 458, 701, 842
Vascular surgeries 820
Vascular system, part of 506
Vasoactive peptides 194
Venous thromboembolism 111, 921
prevention of 219
Ventricular fibrillation 421
Ventricular tachyarrhythmias, development of 434
Ventricular tachycardia 421, 708
Ventricular tachycardia storm 433
Verapamil 66, 567, 739, 812
Vertebral artery disease 599
Very-low-density lipoprotein 9, 50, 72, 169, 201, 204, 267, 289, 292, 293, 330, 337, 452, 468, 527, 561, 724, 734, 779, 780, 820, 872
Vessel wall thickness 672
Visual impairment 771
Vitamin 723, 727
A 190, 719
C 190
D 203, 220, 357, 719
D deficiency 216
isolated 357
D3 163
E 190, 719, 728
K 719
Vitreoretinal disorders, statin in 770
Volanesorsen 250, 252, 308, 352, 353, 910
Vomiting 290
Voriconazole 812
Voyager meta-analysis 129
Vulnerable atherosclerotic plaque 276f
components of 343f
Vulnerable plaque 275277, 320f, 342, 699
W
Waist circumference 332
Wall-motion score index 646
Weakness 66
Wortmannin 133
X
Xanthelasma 81, 85, 780, 780f
Xanthelasmata 14
Xanthine oxidase 190
Xanthomas 367, 779
Y
Yoga 828
and psychosocial management 56
and statin therapy 825, 827
Yolk sac 174
Young hypertensives, cardiovascular risk in 404
Z
Zinc 715
×
Chapter Notes

Save Clear


1Clinical
  1. ACC/AHA Cholesterol Guidelines: How to Handle the High-risk Patients?
  2. Consensus of ESC Lipid Guidelines: What is Applicable for Indians?
  3. Familial Hypercholesterolemia
  4. Understanding and Applying Latest Lipid Guidelines in Clinical Practice
  5. What are Top 6 Cardiovascular Prevention Trials on Lipid Lowering?
  6. Targets in Lipid-lowering Therapy Today
  7. Update on Lipid Management for ASCVD Prevention: What is New in the Cholesterol Guidelines?
  8. The Nuances of Statin Therapy for ASCVD in Clinical Practice
  9. Controversies to Consensus in Classification of Hyperlipidemias and Importance of Statins
  10. How to Enhance Practice and Implementations of Lipid-lowering Guidelines and Adherence?
  11. Comparison of Cholesterol Guidelines in Secondary Prevention and CVD Outcome: What is the Consensus Today?
  12. Current Status, Efficacy, Safety, and Outcome Data of Statin: Atorvastatin versus Rosuvastatin in CVD Outcome
  13. Current Place of Rosuvastatin/Ezetimibe Combination in Management of Hypercholesterolemia
  14. Risk Factors of Dyslipidemia
  15. Pathophysiology of Dyslipidemia
  16. Pleiotropic Effects of Statins and CVD Outcomes
  17. Dyslipidemia in Diabetes: Management Strategies
  18. High-dose versus Low-dose Statins in Cardiovascular Diseases
  19. Statin for Primary Prevention of Cardiovascular Disease
  20. Statin for Tertiary Prevention of Cardiovascular Disease
  21. Dyslipidemia and Statin: An Overview
  22. Efficacy, Safety, and Promising of Atorvastatin versus Rosuvastatin in LDL Cholesterol Reduction Potential and CVD Protection
  23. Statins and Angiogenesis
  24. Statin in Stress-induced Dyslipidemia
  25. Statin in Polyvascular Disease
  26. Statin and Sexual Dysfunction
  27. Statin and Erectile Dysfunction
  28. Statin and Nonalcoholic Steatohepatitis
  29. Statins and Hyperthyroidism
  30. Lipid Lowering in Nonalcoholic Fatty Liver Disease
  31. Statins in Cushing's Syndrome
  32. Statin and Gallstones Disorder
  33. Dyslipidemia in Pregnancy
  34. Statins and Inflammatory Markers
  35. Grow younger and Live Longer with Statin: Effect on Vascular Age
  36. Oxidative Stress and Statin Therapy
  37. Impact of Statins on Endothelium and Vascular Biology
  38. Exercise, Dyslipidemia, and Statin Therapy
  39. Role of Statin Drugs for Polycystic Ovary Syndrome
  40. Statin in Dyslipidemia and Hearing Loss
  41. Statins Intolerance: Is it Really a Problem?
  42. New Insights into Managing Symptoms during Statin Therapy
  43. Nutrition versus Statins: Where do we Stand?
  44. Cholesterol Confusion and Statin Controversy
  45. Statin Therapy in the Perioperative Period
  46. Statin Therapy in Cardiac Intensive Care
  47. Pharmacogenomics of Statin Response
  48. Advances in Statin Therapy and Beyond in Dyslipidemia-inflicted CAD Mortality Reduction
  49. The Controversy of a Wider Statin Utilization
  50. Gender Disparity in Statin Therapy
  51. How Much Statin Intervention is Enough?
  52. Balancing Primary Prevention and Statin-induced Diabetes Prevention
  53. Statin Effect on Atherosclerotic Plaque
  54. All for “Statins” and Statins for All: An “Update”
  55. Triglycerides Reduction Strategies to Prevent CV Events
  56. Statin above the Age of 75 Years: Is it Relevant?
  57. Do Lp(a) Levels Contribute to CVD Risk? What are the Effects of Statin, PCSK9i, LDL Apheresis, and ASOs Therapy?
  58. Morbidity and Mortality Benefits of Statin Therapy in CVD
  59. Novel and Emerging Nonstatin Lipid-lowering Drugs
  60. Diagnostic and Prognostic Markers of Dyslipidemia in CVD2

ACC/AHA Cholesterol Guidelines: How to Handle the High-risk Patients?CHAPTER 1

Bhavuk Jaiswal
GS Wander
 
INTRODUCTION
The latest guidelines by the American College of Cardiology (ACC) and the American Heart Association (AHA) Task Force on clinical practice guidelines for cholesterol management were published in 2018,1 and reviewed in 2019 for primary prevention.2 Compared to 2013, the ACC/AHA cholesterol guidelines3 lay more emphasis on detailed risk assessment. There is a special attention to patient subgroups, consideration of the value of therapy, and an aim of creating personalized treatment plans for each patient. There has been an introduction of newer cholesterol-lowering agents (nonstatin drugs) such as ezetimibe and PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors mainly for secondary prevention in patients at very high risk of atherosclerotic cardiovascular disease (ASCVD) events. In this chapter, we have reviewed the current and previous guidelines and discussed about how to handle the high-risk patients, risk estimation, method of getting lipid profile, and ASCVD risk calculation.
By combining all major risk factors into a prediction equation, an individual's probability of developing ASCVD can be estimated by using ASCVD risk estimator tool. The predicted risk is divided into low risk (<5%), borderline risk (5–7.5%), intermediate risk (≥7.5–20%) and high risk (≥20%) by the ACC/AHA guidelines. The categories with highest overall risk [secondary prevention and primary LDL-C (low-density lipoprotein cholesterol) levels ≥ 190 mg/dL (≥4.9 mmol/L)] require prompt treatment to lower ASCVD risk.1
 
EVALUATION
 
Measurement of Lipid Profile
In adults who are 20 years of age or older and not on lipid-lowering therapy, measurement of either a fasting or a nonfasting plasma lipid profile is effective in estimating ASCVD risk and documenting baseline LDL-C. If the value of triglyceride is >400, a repeat lipid profile in fasting state is recommended. In adults who are 20 years of age or older and without a personal history of ASCVD, but with a family history of premature ASCVD or genetic hyperlipidemia, measurement of a fasting plasma lipid profile is reasonable as part of an initial evaluation to aid in the understanding and identification of familial lipid disorders.
 
Risk Enhancers
Several other factors are associated with increased ASCVD risk. These are called risk-enhancing factors. Projections of future risk derived from major risk factors and risk-enhancing factors can be used to adjust the intensity of LDL-lowering therapy. These are enlisted in Box 1; their presence helps to confirm a higher risk state and thereby supports a decision to initiate or intensify statin therapy. They are useful for clarifying which atherogenic factors are present in a particular patient.
 
MANAGEMENT
 
Nonpharmacological Measures
The management of lipid disorders includes lifestyle therapies including diet management, weight control, and physical activity. Patients should consume a dietary pattern that includes intake of vegetables, fruits, whole grains, and legumes. Healthy protein sources [low-fat dairy products, low-fat poultry (without the skin), fish/seafood, and nuts] can be used. They should limit intake of sweets, sugar-sweetened beverages, and red meats. Caloric intake should be adjusted to avoid weight gain, or in overweight/obese patients, to promote weight loss. Diet remains an important component of management of dyslipidemia.4
However, lipids levels can only be reduced by 10–20% with dietary precautions. These are supplements to statin therapy in high-risk individuals. There is very little role for dietary therapy alone in high-risk individuals. A low-fat and restricted-carbohydrate diet with increased protein intake is important for all Indian patients with dyslipidemia. Indians derive increased fats from whole milk dairy products and these need to be restricted. Indian cooking includes frying and heating of oils. This results in production of trans fats which are harmful. The use of vegetable oils, especially mustard oil and olive oil, is to be encouraged.
Adults should be advised to engage in aerobic physical activity three to four sessions per week, lasting on average 40 minutes per session and involving moderate-to-vigorous-intensity physical activity.
 
Pharmacological Measures
The mainstay of pharmacotherapy is statins. Prior to these the hypolipidemic drugs were weak and did not show significant mortality reduction. This included bile acid sequestrants and fibrates. The bile acid sequestrants had high gastrointestinal (GI) intolerance and caused only modest reduction in LDL. The fibrates (fenofibrate) primarily reduce triglycerides and have little effect on cholesterol and LDL levels. The statin therapy has consistently shown to be effective in reducing mortality in secondary prevention and in high-risk individuals for primary prevention.
TABLE 1   High-, moderate-, and low-intensity statin therapy.
High intensity
Moderate intensity
Low intensity
LDL-C lowering
50%
30–49%
<30%
Statins
Atorvastatin (40 mg) 80 mg
Rosuvastatin 20 mg (40 mg)
Atorvastatin 10 mg (20 mg)
Rosuvastatin (5 mg) 10 mg
Simvastatin 20–40 mg
Simvastatin 10 mg
Pravastatin 40 mg (80 mg)
Lovastatin 40 mg (80 mg)
Pitavastatin 1–4 mg
Pravastatin 10–20 mg
Lovastatin 20 mg
(LDL-C: low-density lipoprotein cholesterol)
 
Statin Therapy
The intensity of statin therapy is divided into three categories: (1) High intensity (lowers LDL-C levels by >50%), (2) moderate intensity (30–49%), and (3) low intensity (<30%) (Table 1). Statin therapy is usually well tolerated and safe. Most frequently occurring statin-associated side effects are statin-associated muscle symptoms (SAMS), new-onset diabetes mellitus, transaminitis, memory/cognition disturbances. The agents used are atorvastatin and rosuvastatin. Rosuvastatin is twice as effective as atorvastatin. These are generally very well tolerated and the risk of new-onset diabetes is very minimal. Even though the muscle symptoms are more often nonorganic, one should do creatine phosphokinase (CPK) levels. In case these are normal patient who need to be reassured and the statins can be continued.
 
Nonstatin Medications
This includes ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. The addition of ezetimibe to a statin regimen increases the magnitude of LDL-C lowering by approximately 15–30%.4,5 The addition of a PCSK9 inhibitor to a statin regimen has been shown to further reduce LDL-C levels by 45–70%.6,7 Ezetimibe reduces cholesterol absorption. It is safe to use and is generally used in 10 mg daily dosage. It has been shown in multiple studies to reduce LDL levels in patients who are already on high-intensity statin therapy. In fact it is the treatment of choice after statins since it is cost effective. The PCSK9 inhibitors are more effective but are very expensive and have to be used by subcutaneous route. Their initiation should be done only after thorough discussion with the patient regarding the cost.5
 
MANAGEMENT ACCORDING TO CLINICAL CONDITION
The management of lipid disorders depends upon the risk of the individual. The high-risk individuals are those with evidence of ASCVD. This includes patients with angina, postmyocardial infarction, postprocedure including percutaneous coronary intervention (PCI) and postcoronary artery bypass grafting (CABG), stroke, and peripheral vascular disease (PVD). Lipid management in these patients is a secondary prevention since all the individual with above disorders have ASCVD. These high-risk patients need high-intensity statins and often addition of other agents. Patients with severe hypercholesterolemia also need treatment. Diabetic patients have higher risk of CAD and threshold for starting lipid-lowering therapy is low. The above three categories are high risk.
Individuals who are at lower level of risk with consideration for primary prevention and other subgroups are also discussed as separate subgroups. The considerations in these five categories are discussed here.
  1. Secondary prevention in ASCVD
  2. Severe hypercholesterolemia
  3. Dyslipidemia in diabetes mellitus
  4. Primary prevention
  5. Other populations at risk
 
Secondary Prevention in ASCVD
The 2018 guidelines defined “very high risk” of future ASCVD events as a history of multiple ASCVD events or one major event plus multiple high-risk conditions as mentioned in Box 2.
In patients younger than 75 years with clinical ASCVD,8 the ACC/AHA strongly recommends high statin therapy in these group of patients whenever possible with goal of reduction in LDL-C levels by ≥50% (Flowchart 1). This percentage can be used to judge clinical efficacy. Absolute benefit from statin therapy depends on baseline LDL-C levels. The greatest absolute benefit occurs in patients with the highest baseline LDL-C levels. Percentage reduction of LDL-C levels is the most efficient means to estimate expected efficacy. In patients with clinical ASCVD in whom high-intensity statin therapy is contraindicated or who experience statin-associated side effects, moderate-intensity statin therapy should be initiated or continued with the aim of achieving a 30–49% reduction in LDL-C levels. Guidelines also make a strong recommendation for clinicians to add ezetimibe to maximally tolerated statin therapy as a first step in lowering LDL-C further as depicted in Flowchart 1. In patients with clinical ASCVD who are judged to be very high risk and considered for PCSK9 inhibitor therapy when the LDL remains high despite maximally tolerated statin therapy and ezetimibe.
 
Severe Hypercholesterolemia
Patients with primary severe hypercholesterolemia [LDL-C levels ≥ 190 mg/dL (≥4.9 mmol/L)] have a high lifetime risk of ASCVD and decisions about statins in these patients do not require risk scoring. Patients with very high LDL-C ≥ 190 mg/dL (≥4.9 mmol/L) values are most likely to achieve the greatest benefit from evidence-based LDL-C-lowering therapy regardless of genetic mutation associated with familiar hypercholesterolemia (FH). Maximally tolerated statin therapy should be administered to patients with primary severe hypercholesterolemia as high-intensity statins provide greater ASCVD risk reduction than moderate-intensity statins or placebo. Bile acid sequestrants may be considered in patients with severe hypercholesterolemia who are taking maximally tolerated statins with or without ezetimibe with less than a 50% reduction in LDL-C levels and have fasting triglycerides ≤ 300 mg/dL. Addition of a PCSK9 inhibitor may be considered in patients who have a baseline LDL-C level ≥ 220 mg/dL (≥5.7 mmol/L) and an on-treatment LDL-C level ≥ 130 mg/dL (≥3.4 mmol/L) despite maximally tolerated statin and ezetimibe therapy after a clinician–patient discussion of the net benefits versus the costs of such therapy.
 
Dyslipidemia in Diabetes Mellitus
High-intensity statin therapy to maximize risk reduction is preferred for patients with diabetes mellitus at any age or if they have risk modifiers as mentioned in Box 3. Adults of 40–75 years of age with diabetes mellitus are at an intermediate or high-risk of their first ASCVD event and regardless of estimated 10-year ASCVD risk, moderate-intensity statin therapy is indicated. The occurrence of a first ASCVD event in patients of 40–75 years of age with diabetes mellitus is associated with increased morbidity and mortality compared with those without diabetes mellitus, which places a particularly high premium on primary prevention in those with diabetes mellitus in that age range; therefore, it is 6reasonable to prescribe high-intensity statin therapy with the aim to reduce LDL-C levels by 50% or more.
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Flowchart 1: Secondary prevention in patients with ASCVD.(ASCVD: atherosclerotic cardiovascular disease; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; PCSK9: proprotein convertase subtilisin-kexin type 9: RCT: randomized controlled trial)
Further ezetimibe can be added to maximally tolerated lipid-lowering therapy in patients with diabetes mellitus and 10-year ASCVD risk of 20% or higher to reduced LDL-C by 50% or greater.
 
Primary Prevention
The 2019 ACC/AHA guidelines on the primary prevention of cardiovascular disease addresses major issues related to cholesterol management and primary ASCVD prevention. Three major higher-risk categories are patients with:
  1. Severe hypercholesterolemia [LDL-C levels ≥ 190 mg/dL (≥4.9 mmol/L)]
  2. Adults with diabetes mellitus
  3. Adults of 40–75 years of age
Patients with severe hypercholesterolemia and adults of 40–75 years of age with diabetes mellitus are candidates for immediate statin therapy without further risk assessment (Flowchart 2). Adults with diabetes mellitus should start with a moderate-intensity statin, and if they have multiple risk factors, a high-intensity statin may be indicated. In other adults of 40–75 years of age, 10-year ASCVD risk should guide therapeutic considerations. The higher the estimated ASCVD risk, the more likely the patient is to benefit from evidence-based statin treatment. The risk discussion should also consider several “risk enhancers” (Box 1) that can be used to favor initiation or intensification of statin therapy. When risk is uncertain or if statin therapy is problematic, it can be helpful to measure coronary artery calcium (CAC) to refine risk assessment. The CAC score predicts ASCVD events in a graded fashion and is independent of other risk factors, such as age, sex, and ethnicity. Most patients with CAC scores ≥ 100 Agatston units have a 10-year risk of ASCVD ≥7.5%, a widely accepted threshold for initiation of statin therapy (Flowchart 2).7
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Flowchart 2: The 2018 cholesterol clinical practice guidelines for primary prevention.(apoB: apolipoprotein B; ASCVD: atherosclerotic cardiovascular disease; hs-CRP: high-sensitivity c-reactive protein; CAC: coronary artery calcium; CRP: high-sensitivity C-reactive protein; LDL-C: low-density lipoprotein cholesterol; Lp(a): lipoprotein a
 
Other Groups
Older adults: Older adults are more susceptible to statin-related risks. In adults of 75 years of age or older with an LDL-C level of 70–189 mg/dL, initiating moderate-intensity statin may be reasonable.
Young adults (20–39 years): Development of atherosclerosis in young adults most commonly is multifactorial and occurs most rapidly in individuals with multiple risk factors such as hypercholesterolemia, hypertension, cigarette smoking, diabetes mellitus, and obesity. Young adults with primary elevations of LDL-C ≥ 190 mg/dL have a long-term ASCVD burden and statin therapy is recommended. Young adults with persistent, moderate hypercholesterolemia (LDL-C 160–189 mg/dL) are at a higher risk, especially when associated with risk-enhancing factors, such as a family history of premature ASCVD. Clinical judgment suggests that these high-risk young adults will benefit from long-term statin therapy.
Children and Adolescents: In children and adolescents with a family history of either early CVD or significant hypercholesterolemia [LDL-C ≥190 mg/dL (≥4.9 mmol/L) with known primary hypercholesterolemia], it is reasonable to measure a fasting or nonfasting lipoprotein profile as early as age 2 years to detect FH or rare forms of hypercholesterolemia. In children and adolescents of 10 years of age or older with an LDL-C level persistently 190 mg/dL or higher (≥4.9 mmol/L) or 160 mg/dL or higher (4.1 mmol/L) with a clinical presentation consistent with FH and who do not respond adequately with 3–6 months of lifestyle therapy, it is reasonable to initiate statin therapy.
Ethnicity: It is reasonable for clinicians to review race/ethnic features that can influence the ASCVD risk, intensity of treatment and even lipid drug doses. Important examples include the heightened risk of ASCVD in those who are from South Asian race. There is an increased sensitivity to statins in East Asians. The prevalence of hypertension is higher in blacks.
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  1. 8 Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the primary prevention of cardiovascular disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74(10):e177–232.
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