Slide Source: Lipids Online Slide Library High-Density Lipoprotein and the Epidemiology of Coronary Heart Disease Michael Miller,

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


Distribution and Prevalence of Low Distribution and Prevalence of Low Levels of High-Density Lipoprotein Levels of High-Density Lipoprotein CholesterolCholesterol


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.


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


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


Distribution of Low HDL-C Levels in NHANES IIIDistribution of Low HDL-C Levels in NHANES III

0

2

4

6

8

10

12

14

16

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


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


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.


Low High-Density Lipoprotein Cholesterol and Coronary Heart Disease Risk


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


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.


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


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)


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


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


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.


Statin Treatment and Low High-Density Lipoprotein Cholesterol


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


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


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


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.


On-Treatment Level of High-Density Lipoprotein Cholesterol in the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT)


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


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

Slide Source: Lipids Online Slide Library High-Density Lipoprotein and the Epidemiology of Coronary Heart Disease Michael Miller,

Documents

slide source

faha slide

level slide

lipids online slide

hdlc mgdl

hdlc distribution

low tgs low hdlc

ldlc mgdl