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Slide Source:Lipids Online Slide Librarywww.lipidsonline.org
High-Density Lipoprotein and the High-Density Lipoprotein and the Epidemiology of Coronary Heart Epidemiology of Coronary Heart Disease Disease
Michael Miller, MD, FACC, FAHAMichael Miller, MD, FACC, FAHA
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Distribution and Prevalence of Low Distribution and Prevalence of Low Levels of High-Density Lipoprotein Levels of High-Density Lipoprotein CholesterolCholesterol
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Normal Values for Plasma Concentrations of Normal Values for Plasma Concentrations of High-Density Lipoprotein Cholesterol*High-Density Lipoprotein Cholesterol*
NORMAL VALUES (mg/d)
MALES (percentages) FEMALES (percentages)
AGE (yrs) 10 25 50 10 25 50
5–9 42 49 54 10 47 5010–14 40 46 55 40 45 5215–19 34 39 46 38 43 5120–24 32 38 45 37 43 5025–29 32 37 44 40 47 5530–34 32 38 45 40 46 5535–39 31 36 43 38 44 5240–44 31 36 43 39 48 5545–49 33 38 45 39 46 5650–54 31 36 44 40 49 5955–59 31 38 46 39 47 5860–64 34 41 49 38 46 6065–69 33 39 49 38 46 6070+ 33 40 48 37 48 60
NHLBI. In: The Lipid Research Clinics Population Studies Data Book. Vol 1. 1980. NIH publication 80-1527.
*Values are based on population-based studies conducted the United States and Canada. Data on 3,524 white males and 2,545 white females (nonusers of sex hormones) are derived from NIH publication 80-1527. All subjects were sampled in the fasting state.
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Ethnic Variations in Lipid Parameters:Ethnic Variations in Lipid Parameters:Insulin Resistance Atherosclerosis StudyInsulin Resistance Atherosclerosis Study
African-Americans Hispanics
Non-Hispanic Whites P Value
n (%) 462 (27) 546 (34) 612 (38) < 0.001
Total-C (mg/dL) 212.5 211.1 213.2 0.782
LDL-C (mg/dL) 143.8 139.4 140.7 0.410
HDL-C (mg/dL) 47.0 42.3 44.0 < 0.001
TGs (mg/dL) 102.1 147.7 134.0 < 0.001
LDL size (Å) 262.1 257.6 259.2 < 0.001
Haffner SM, et al. Arterioscler Thromb Vasc Biol. 1999;19:2234-2240.
C = cholesterol; LDL = low-density lipoprotein; HDL = high-density lipoprotein;TGs = triglycerides
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HDL-C Distribution in U.S. AdultsHDL-C Distribution in U.S. Adults
NCHS. NHANES III data files, documentation, and SAS code. http://www.cdc.gov/nchs/about/major/nhanes/nh3data.htm.
0
2
4
6
8
10
12
14
16
No.
of
U.S
. A
dult
s (m
illio
ns)
CHDCHD
≥ ≥2 RFs;2 RFs; no CHDno CHD
RFs = risk factors; CHD = coronary heart disease;HDL-C = high-density lipoprotein cholesterol
<35<35
HDL-C (mg/dL)
35 to <4535 to <45 45 to <6045 to <60 ≥≥6060
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Distribution of Low HDL-C Levels in NHANES IIIDistribution of Low HDL-C Levels in NHANES III
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18
Pop
ula
tion (
%)
Men
Women
5-9
Miller M, et al. Curr Opin Cardiol. 2004;19:380–384.
30-34
HDL-C (mg/dL)
10-14 15-19 20-24 25-29 35-39
HDL-C = high-density lipoprotein cholesterolNHANES = National Health and Nutrition Examination Survey
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NHANES III:NHANES III:Prevalence of Low Levels of HDL-C and Prevalence of Low Levels of HDL-C and Low or High Levels of TriglyceridesLow or High Levels of Triglycerides
Low HDL-C* and Low TGs†
Low HDL-C* andHigh TGs‡
Age (yr) n Men (%) Women (%) Men (%) Women (%)
20–34 3,047 7.4§ 20.0 6.9§ 4.7§
35+ 6,234 4.8 8.7 12.7 12.6
*Level <40 mg/dL in men and <50 mg/dL in women†Level <100 mg/dL‡Level ≥200 mg/dL§ p < 0.0005, as derived from a chi square analysis of the two age groups
Reprinted from Miller M, et al. Atherosclerosis. 2003;169:347–348,with permission from Wolters Kluwer Health.
HDL-C = high-density lipoprotein cholesterolNHANES = National Health and Nutrition Examination SurveyTGs = triglycerides
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NHANES III: Prevalence of Isolated Low HDL-C*NHANES III: Prevalence of Isolated Low HDL-C*
Age n Men Women
20–34 3,047 2.5% 8.8%
35–44 1,721 2.2% 5.5%
45–54 1,076 1.6% 1.6%
55–64 1,133 1.3% 2.1%
65–74 1,143 1.7% 1.1%
75+ 1,161 2.4% 1.0%
Modified from Miller M. In: Clinical Lipidology: A Companion to Braunwald's Heart Disease. 2009;119-129.
HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; NHANES = National Health and Nutrition Examination Survey
*Cut points: HDL-C <40 mg/dL in men and <50 mg/dL in women; triglycerides <150 mg/dL; and LDL-C < 100 mg/dL.
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Low High-Density Lipoprotein Cholesterol and Coronary Heart Disease Risk
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Coronary Heart Disease Risk According to Coronary Heart Disease Risk According to HDL-C Levels: HDL-C Levels: The Framingham Heart StudyThe Framingham Heart Study
Kannel WB. Am J Cardiol. 1983;52:9B–12B.
CH
D R
isk
Rati
o
HDL-C (mg/dL)
0.0
1.0
2.0
3.0
4.0
25 45 65
2.0
1.0
4.0
CHD = coronary heart disease; HDL-C = high-density lipoprotein cholesterol
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Coronary Heart Disease Risk According Coronary Heart Disease Risk According to HDL-C Levels: to HDL-C Levels: The PROCAM StudyThe PROCAM Study
186 CHD Events* in 4,407 Men Aged 40–65 Years
HDL-C Tertile(mg/dL)
Observed CHDEvents (per 100)
Incidence of CHD Events at 6 Years
(per 1,000)
< 35 77 110†
3–55 27 30
> 55 26 21
*134 definite nonfatal myocardial infarctions and 52 definite atherosclerotic CHD-related deaths
†Approximately a 4-fold increased risk of CHD at 6 years for this tertile
CHD = coronary heart disease; HDL-C = high-density lipoprotein cholesterol; PROCAM = Prospective Cardiovascular Münster Study
Assmann G, Schulte H. In: Lipid Metabolism Disorders and Coronary Heart Disease. 1993;19-68.
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Distribution of HDL-C Levels in Distribution of HDL-C Levels in Men With Coronary Heart Disease: Men With Coronary Heart Disease: VA-HIT Study GroupVA-HIT Study Group
HDL-C Level(mg/dL)
Whites(n = 2,891)
Blacks(n = 572)
All subjects(N = 8,578)
<35 42% 20% 38%
35-40 25% 23% 25%
>40 32% 57% 36%
Rubins HB, et al. Am J Cardiol. 1995;75:1196–1201.
63%
HDL-C = high-density lipoprotein cholesterol; VA-HIT = Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial
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Frequency of Low HDL-C When Compared With Frequency of Low HDL-C When Compared With Other Risk Factors in Men With Premature Other Risk Factors in Men With Premature Coronary Heart DiseaseCoronary Heart Disease
Cases(n = 321)
Risk FactorControls(n = 601) Not Adjusted Adjusted
Cigarette smoking 29% 67%* —
HDL-C <35 mg/dL 19% 63%* 57%*
Hypertension (BP >150/90) 21% 41%* —
LDL-C >160 mg/dL 26% 26% 34%*
Diabetes mellitus 1% 12%* —
Reprinted form Genest JJ, et al. Am J Cardiol. 1991;67:1185–1189, with permission from Elsevier.
BP = blood pressure; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol
*Significantly different from controls (P <0.001)
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0.0
1.0
2.0
3.0
Low HDL-C Predicts Coronary Heart Low HDL-C Predicts Coronary Heart Disease Risk Independent of LDL-C:Disease Risk Independent of LDL-C:The Framingham Heart StudyThe Framingham Heart Study
100
Relative Risk of Coronary
Heart Disease
After 4 Years
25
LDL-C (mg/dL)
160 22085
6545
HDL-C(mg/dL)
Data for men aged 50–70 years
Reproduced with permission from Castelli WP. Can J Cardiol. 1988;4(Suppl A):5A-10A. Copyright © 1988 Pulsus Group Inc.
HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol
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Hypertriglyceridemia Increases CHD Hypertriglyceridemia Increases CHD Risk in Patients With Low HDL-C Levels:Risk in Patients With Low HDL-C Levels:The PROCAM StudyThe PROCAM Study
Assmann G, Schulte H. Am J Cardiol. 1992;70:733–737.
0
50
100
150
200
250
Inci
dence
per
1,0
00
(in
6 y
ears
)
≤ 5.0
LDL-C / HDL-C Ratio
> 5.0
TG < 200 mg/dL
TG ≥ 200 mg/dL245
31
116
24
***Bar represents 5% of subjects in which 25% of CHD events occurred
CHD = coronary heart disease; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PROCAM = Prospective Cardiovascular Münster (PROCAM) Study; TG = triglycerides
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Coronary Heart Disease Incidence Is Related Coronary Heart Disease Incidence Is Related to HDL-C Levels in Various Clinical Trialsto HDL-C Levels in Various Clinical Trials
*95% confidence intervals for adjusted proportional hazards regression coefficients.
-10
-8
-6
-4
-2
0
% C
hange in R
isk
per
Incr
em
ents
(1 m
g/d
L)in
HD
L-C
*
FHS LRCF CPPT MRFIT FHS LRCF
CHD Incidence
Men Women
CHD = coronary heart disease; HDL-C = high-density lipoprotein cholesterol
Gordon DJ, et al. Circulation. 1989;79:8-15.
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Statin Treatment and Low High-Density Lipoprotein Cholesterol
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Effect of Fluvastatin on Coronary Effect of Fluvastatin on Coronary Angiographic Progression in Patients Angiographic Progression in Patients With Low HDL-C:With Low HDL-C: The LCAS The LCAS
Reprinted from Ballantyne CM, et al. Circulation 1999;99: 736–743, with permission from Wolters Kluwer Health.
0.000
0.040
0.080
0.120
0.160
0.200
0.240
0.280
0.320
Pro
gre
ssio
n
(MLD
Decr
ease
in
mm
)
n=43
Fluvastatin
Placebo
n=25 n=128 n=143
p=0.01
HDL-C <35 mg/dL (p=0.0004)
HDL-C ≥35 mg/dL (p=0.09)
HDL-C = high-density lipoprotein cholesterol; LCAS = Lipoprotein and Coronary Atherosclerosis Study; MLD = minimum lumen diameter
0.065
0.274
0.036
0.083
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Reduced Coronary Heart Disease Risk Is Reduced Coronary Heart Disease Risk Is Associated With Low HDL-C: Associated With Low HDL-C: Statin TrialsStatin Trials
Ballantyne CM. et al. Prev Cardiol. 2001;4:65–72. Copyright © 2002 by Le Jacq Communications Inc. Reproduced with permission of Blackwell Publishing Ltd.
0
5
10
15
20
25
30
35
Coro
nary
Even
ts (
%)
HDL-C (mg/dL)
≥43≥52
Statin
Placebo
≤38 ≥39 <39 >44 <33 <43 ≥40 ≤34
WOSCOPS4S LIPID CARE AFCAPS/TexCAPS
HDL-C = high-density lipoprotein cholesterol
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Baseline HDL-C Quartiles and Relative Risk for Baseline HDL-C Quartiles and Relative Risk for Coronary Heart Disease: Coronary Heart Disease: The MIRACL TrialThe MIRACL Trial
0.0
0.2
0.4
0.6
0.8
1.0
Rela
tive R
isk
<38
Quartile of Baseline HDL-C (mg/dL)
Olsson AG, et al. Eur Heart J. 2005;26:890-896.
0.62
38–44 45–52 >53
0.820.90
1.00
HDL-C = high-density lipoprotein cholesterol; MIRACL = Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering
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Low HDL-C Increases Cardiovascular Disease Low HDL-C Increases Cardiovascular Disease Risk Even If LDL-C Levels Are Well-controlled: Risk Even If LDL-C Levels Are Well-controlled: The Treating to New Targets StudyThe Treating to New Targets Study
0
2
4
6
8
10
Q1 Q2 Q3 Q4 Q5
5-Y
ear
Ris
k of
Majo
r C
ard
iovasc
ula
r D
isease
E
ven
ts (
%)
HDL-C quintiles*(mg/dL)
*On-treatment level (3 months statin therapy)†Mean low-density lipoprotein cholesterol (LDL-C) level = 58 mg/dL; mean triglyceride (TG) level = 126 mg/dL
‡P=.03 for differences among quintiles of HDL-C
Patients (n = 2661) with LDL-C <70 mg/dL on a Statin*†
37 to <42 42 to <47 42 to <55 >55<37
0.85 0.57 0.55 0.61Hazard Ratio vs. Q1‡
Barter P, et al. N Engl J Med. 2007;357:1301-1310.
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On-Treatment Level of High-Density Lipoprotein Cholesterol in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT)
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Relation of Coronary Heart Disease Relation of Coronary Heart Disease to On-Trial HDL-C Level: to On-Trial HDL-C Level: VA-HITVA-HIT
Robins SJ, et al. JAMA 2001;285:1585–1591. Copyright © 2001,American Medical Association. All rights reserved.
CH
D R
isk
Rate
(%
)
HDL-C (mg/dL)
10
14
18
22
26
25 29 413733
Placebo
Gemfibrozil
CHD = coronary heart disease; HDL-C = high-density lipoprotein cholesterol;VA-HIT = Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial
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Low HDL-C is a risk factor for coronary heart disease, irrespective of LDL-C.
Elevated LDL-C and triglyceride levels greatly enhance coronary heart disease risk in patients with low HDL-C.
Observational studies suggest that each 1-mg/dL incremental increase in HDL-C is associated with a 2–3% reduction in coronary heart disease risk.
Statin therapy attenuates the excess coronary heart disease risk that is associated with low HDL-C, but there is a caveat. Event rates remain higher in patients who have low levels of HDL-C at baseline when compared to those who have higher levels of HDL-C — even when patients are treated with statins.
HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol
HDL-C and the Epidemiology of HDL-C and the Epidemiology of Coronary Heart Disease: Coronary Heart Disease: SummarySummary