Cardiovascular Risk Factor Overview and Management Nathan D. Wong, PhD, FACC Associate Professor and Director, Heart Disease Prevention Program, University.

Cardiovascular Risk Factor Overview and Management

Nathan D. Wong, PhD, FACC

Associate Professor and Director,

Heart Disease Prevention Program, University of California, Irvine

Cardiovascular Disease: The Leading Cause of Death in US Women in 1995

9.9

33.1

31.9

43.8

45.1

48.9

60.6

96.4

375

0 50 100 150 200 250 300 350 400Deaths (1,000)

Ovarian cancer

Diabetes

Accidents

Breast cancer

Pneumonia/Influenza

COPD*

Lung cancer

Cerebrovascular disease

Heart disease

*COPD=chronic obstructive pulmonary disease. Adapted from Anderson RN et al. Monthly Vital Statistics Report.Vol 45(suppl 2):June 12, 1997.

• CHD is the single largest killer of men and women

• ~13.9 million have history of MI and/or angina

• Each year 1.1 million people have MI

– 370,000 die of MI, 250,000 die within 1 hr

• By age 60, every 5th man and 17th woman develops CHD

• 1998 estimated direct and indirect costs of heart disease are $95.6 billion

• 53.3 million adults have elevated LDL-C and warrant intervention (1994 NHANES data)

– 22.3 million qualify for drug therapy, 5.5 million receive therapy

AHA. 1998 Heart and Stroke Statistical Update; 1997.National Center for Health Statistics. National Health and Nutrition Examination Survey (III); 1994. (Data collected 1991-1994.)

CHD in the United States

CVD Mortality Trends for Males and Females*

1979 199681 83 85 87 89 91 93 95

20

0

420

440

460

480

500

520

Deaths inthousands

Males Females

Years

*United States: 1979-1996 mortality.

AHA. 1999 Heart and Stroke Statistical Update; 1998.

PDAY: Percentage of Right Coronary Artery Intimal Surface Affected With Early Atherosclerosis

PDAY=PDAY= Pathobiological Determinants of Atherosclerosis in Youth.Strong JP, et al. JAMA. 1999;281:727-735.

Fatty streaks

Raised lesions

White15-19 20-24 25-29 30-34

0

10

20

30 Women

0

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20

30

15-1920-2425-2930-34

Black

Age (y)

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White15-19 20-24 25-29 30-34

Men

Black15-19 20-24 25-29 30-34

0

10

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Intimalsurface

(%)

Beyond Cholesterol: Predicting Cardiovascular Risk In the 21st Century

Cardiovascular RiskCardiovascular RiskCardiovascular RiskCardiovascular Risk

LipidsLipidsHTNHTN

DiabetesDiabetes

LipidsLipidsHTNHTN

DiabetesDiabetesBehavioralBehavioralBehavioralBehavioral HemostaticHemostatic

ThromboticThromboticHemostaticHemostaticThromboticThrombotic InflammatoryInflammatoryInflammatoryInflammatory GeneticGeneticGeneticGenetic

Continuum of Patients at Risk for a CHD Event

Post MI/Angina

Other Atherosclerotic Manifestations

Subclinical Atherosclerosis

Multiple Risk Factors

Low Risk

SecondaryPrevention

PrimaryPrevention

Courtesy of CD Furberg.

Total Cholesterol Distribution: CHD vs Non-CHD Population

Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.1996 Reprinted with permission from Elsevier Science.

35% of CHD 35% of CHD Occurs in Occurs in People with People with TC<200 mg/dLTC<200 mg/dL

150 200

Total Cholesterol (mg/dL)

250 300

No CHD

CHD

Framingham Heart Study—26-Year Follow-up

Low HDL-C Levels Increase CHD Risk Even When Total-C Is Normal (Framingham)

Risk of CHD by HDL-C and Total-C levels; aged 48–83 yCastelli WP et al. JAMA 1986;256:2835–2838

02468

101214

< 40 40–49 50–59 60< 200

230–259200–229

260

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l-C (m

g/dL

)

14

-y in

cid

en

ce

rate

s (%

) fo

r C

HD

11.24

11.91

12.50

11.91

6.56

4.67

9.05

5.53

4.85

4.153.77

2.782.06

3.83

10.7

6.6

CHD Incidence Related to HDL-C Levels in Various Trials

95% confidence intervals (CIs) for adjusted proportional hazards regression coefficients. Gordon DJ et al. Circulation 1989;79:8–15

% c

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ge in

ris

k p

er

1 m

g/d

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en

t in

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L-C

0

-2

-4

-6

-8

-10

FHSLRCF

CPPTMRFIT FHS

LRCF

CHD incidenceMen Women

Gould AL et al. Circulation. 1998;97:946-952.

Clinical Benefits of Cholesterol Reduction

• A recent meta-analysis of 38 trials demonstrated that for every 10% reduction in TC– CHD mortality decreased by 15% (P<0.001)– total mortality decreased by 11% (P<0.001)

• Decreases were similar for all treatment modalities• Cholesterol reduction did not increase non-CHD

mortality

Major CHD Risk Factors Other Than LDL-C According to NCEP ATP-III

Positive risk factors• Age

– male 45

– female 55

• Family Hx of CHD: 1st-degree relative with MI or sudden cardiac death - male relative: <age 55

– female relative: <age 65

• Current cigarette smoking

• Hypertension: BP 140/90 mm Hg or on antihypertensive meds

• Low HDL-C: <40 mg/dL

• Diabetes IS A CHD QUIVALENT IDENTIFYING PT AS HIGH RISK

Negative risk factor

• High HDL-C: 60 mg/dL

Other Recognized Risk Factors

• Obesity: traditionally determined by body mass index >30 kg/m2 with overweighted defined as 25-<30 kg/m 2.

• Abdominal obesity involves waist circumference >40 in. in men, >35 in. in women

• Physical inactivity: various definitions

JNC VI: Risk Stratification and Treatment*

JNC VI. November 1997:chapter 2. NIH publication 98-4080.

Group A Group B Group C

Uncomplicated HTN HTN w/Risk Factors TOD/ CCD/ Diabetes

High-normal Lifestyle Lifestyle Drug therapy‡

(130-139/85-89) modification modification

Stage 1 Lifestyle Lifestyle Drug therapy(140-159/90-99) modification modification†

(up to 12 mo) (up to 6 mo)

Stages 2 and 3 Drug therapy Drug therapy Drug therapy(160/ 100)

Probability of Death From CHD in Patients With NIDDM and in Nondiabetic Patients,

With and Without Prior MI

Kaplan-Meier estimatesHaffner SM et al. N Engl J Med 1998;339:229–234

0 1 2 3 4 5 6 7 80

20

40

60

80

100

Nondiabetic subjects without prior MI

Diabetic subjects without prior MI

Nondiabetic subjects with prior MI

Diabetic subjects with prior MI

Years

Surv

ival (%

)

Definitions of Diabetes and Impaired Fasting Glucose

• New ADA definition (1998) defines fasting blood sugar of > 126 mg/dl as diabetes, casual blood glucose > 200 mg/dl. Impaired fasting glucose is 110-125 mg/dl

• Diabetic control generally defined as HgbA1c <8%.

• BP recommended <130/80 mmHg, LDL-C goal <100 mg/dl

Secondary CHD Prevention in Women: Results from the CARE Trial

• CARE was a secondary prevention trial of pravastatin versus placebo treatment in 4159 men and women with average lipid levels over 5 years

• 576 post-menopausal women were randomized; average age 61; 10% on HRT

• Average baseline lipids: TC 215 mg/dL, LDL-C 140 mg/dL, HDL 45 mg/dL

• 5 year treatment results: 46% reduction in all coronary events, 48% reduction in PTCA, 40% reduction in CABG, 56% reduction in stroke

JACC 1998;32:140-146

Heart and Estrogen/Progestin Replacement Study (HERS): Secondary Prevention of CHD

in Women

• Randomized, placebo-controlled trial of E/P therapy vs. placebo in 2763 women with CHD; average age 67 years

• Treatment was 0.625 mg CEE + 2.5 mg medroxyprogesterone daily for 4 years

• Primary endpoint: nonfatal MI and CHD death• Secondary endpoints: CABG, PTCA, unstable

angina, CHF, PVD, TIA

JAMA 1998;280:605-613

HERS Results• Non-fatal MI HRT 116 Placebo 129

CHD death HRT 71 Placebo 58

• End of Year 1 CHD events (HRT) 42.5/1000 women-years

CHD events (Plac) 28/1000 women-years

• Year 4-5: CHD events (HRT) 23/1000 women-years

CHD events (Plac) 34.3/1000 women-years

• DVT/PE HRT 6.3 vs. Plac 2.2

Cholelithiasis HRT 84 vs. Plac 62

JAMA 1998;280:605-613

JAMA 1998;280:605-613

HERS Results• No statistically significant difference between HRT

and placebo in both primary and secondary endpoints after 4 years.

• Within first year, greater incidence in CHD events in HRT group. In years 3 and 4, lower CHD events in HRT group compared to placebo.

• HRT lowered LDL 11% and increased HDL 10% compared to placebo.

• Approximately 50% of randomized women were on lipid-lowering drugs.

• Higher incidence of VTE and cholelithiasis in HRT group.

Is there clinical evidence that Is there clinical evidence that

inflammatory markers predict future inflammatory markers predict future

coronary events and provide additional coronary events and provide additional

predictive information beyond predictive information beyond

traditional risk factors?traditional risk factors?

0

1

2

3

hs-CRP and Risk of Future MI in Apparently Healthy Men

Ridker PM et al. N Engl J Med 1997;336:973-979.

1<0.055

Rela

tive R

isk

of

MI

P = 0.03

Quartile of hs-CRP (range, mg/dL)

20.056–0.114

30.115–0.210

4>0.211

P < 0.001

P < 0.001

PP Trend Trend <0.001<0.001

0

1

2

3

4

5

6

7

hs-CRP and Risk of Future Cardiovascular Events in Apparently Healthy Women

Ridker PM et al. Circulation 1998;98:731-733.

1<0.15

Rela

tive R

isk

Quartile of hs-CRP (range, mg/dL)

20.15–0.37

30.37–0.73

4>0.73

PP Trend Trend <0.002<0.002

Any Event

MI or Stroke

Lp(a) in Atherogenesis: Another Culprit?

• Identical to LDL particle except for addition of apo(a)

• Plasma concentration predictive of atherosclerotic disease in many epidemiologic studies, although not all

• Accumulates in atherosclerotic plaque

• Binds apo B-containing lipoproteins and proteoglycans

• Taken up by foam cell precursors

• May interfere with thrombolysis

Maher VMG et al. JAMA. 1995;274:1771-1774.Stein JH, Rosenson RS. Arch Intern Med. 1997;157:1170-1176.

Lp(a): An Independent CHD Risk Factor in Men of the Framingham Offspring Cohort

RR=relative risk; HT=hypertension; GI=glucose intolerance.

Bostom AG et al. JAMA. 1996;276:544-548.

1.9 1.8 1.81.2

2.73.6

RR

0.1

1

10

2

5

0.2

0.5 Lp(a) TC HDL-C HT GISmoking

Homocysteine: Role in Atherogenesis• Linked to pathophysiology of arteriosclerosis in 1969

• CVD patients have elevated levels of plasma homocysteine

• May cause vascular damage to intimal cells

• Elevated levels linked to:

– genetic defects

– exposure to toxins

– diet

• Increased dietary intake of folate and vitamin B6 may reduce CVD morbidity and mortality

Guide to Primary Prevention of Cardiovascular Diseases

Risk Intervention Recommendations

Smoking: Goal complete cessation

Ask about smoking status as part of routineevaluation. Reinforce nonsmoking status.

Strongly encourage patient and family to stopsmoking.

Provide counseling, nicotine replacement, andformal cessation programs as appropriate.

Blood pressurecontrol: Goal <140/90 mm Hg or <130/85 mm Hg if heart failure, renalinsufficiency or diabetes

Measure blood pressure in all adults at least every 2years.

Promote lifestyle modification: weight control,physical activity, moderation in alcohol intake, andmoderate sodium restriction.

If blood pressure 140/90 mm Hg after 3 months oflifestyle modification or if initial blood pressure>160/100 mm Hg or >130/85 mm Hg with heartfailure, renal insufficiency or diabetes, add bloodpressure medication. Individualize therapy topatient's age, race, need for drugs with specificbenefits, etc.C:\My Documents\Guide to Primary Prevention ofCardiovascular Diseases.doc - T1

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