Transcript Cardiovascular Risk Factor Overview and Management

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
Heart disease
375
Cerebrovascular disease
96.4
Lung cancer
60.6
COPD*
48.9
Pneumonia/Influenza
45.1
Breast cancer
43.8
Accidents
31.9
Diabetes
33.1
Ovarian cancer
9.9
0
50
100 150 200 250 300 350 400
Deaths (1,000)
*COPD=chronic obstructive pulmonary disease.
Adapted from Anderson RN et al. Monthly Vital Statistics Report.
Vol 45(suppl 2):June 12, 1997.
CHD in the United States
• 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.)
CVD Mortality Trends for Males and
Females*
520
500
480
Deaths in
460
thousands
440
420
20
0
1979 81
83
85
87 89
Years
Males
*United States: 1979-1996 mortality.
AHA. 1999 Heart and Stroke Statistical Update; 1998.
91
93
Females
95 1996
PDAY: Percentage of Right Coronary Artery Intimal
Surface Affected With Early Atherosclerosis
30
Intimal
surface
(%)
Men
Raised lesions
Fatty streaks
30
20
20
10
10
0
30
0
15-19 20-24 25-29 30-34
White
30
20
20
10
10
0
0
15-19 20-24 25-29 30-34
Black
Women
15-19 20-24 25-29 30-34
White
15-1920-2425-2930-34
Black
Age (y)
PDAY= Pathobiological Determinants of Atherosclerosis in Youth.
Strong JP, et al. JAMA. 1999;281:727-735.
Beyond Cholesterol: Predicting Cardiovascular
Risk In the 21st Century
Cardiovascular Risk
Lipids
HTN
Diabetes
Behavioral
Hemostatic
Inflammatory Genetic
Thrombotic
Continuum of Patients at Risk for a
CHD Event
Secondary
Prevention
Post MI/Angina
Other Atherosclerotic
Manifestations
Primary
Prevention
Subclinical
Atherosclerosis
Multiple Risk
Factors
Low Risk
Courtesy of CD Furberg.
Total Cholesterol Distribution:
CHD vs Non-CHD Population
Framingham Heart Study—26-Year Follow-up
No CHD
35% of CHD
Occurs in
People with
TC<200 mg/dL
CHD
150
200
250
300
Total Cholesterol (mg/dL)
Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.
1996 Reprinted with permission from Elsevier Science.
14-y incidence
rates (%) for CHD
Low HDL-C Levels Increase CHD Risk Even
When Total-C Is Normal (Framingham)
14
12
10
8
6
4
2
0
< 40 40–49 50–59  60
HDL-C (mg/dL)
 260
230–259
200–229
< 200
Risk of CHD by HDL-C and Total-C levels; aged 48–83 y
Castelli WP et al. JAMA 1986;256:2835–2838
% change in risk per 1 mg/dL
increment in HDL-C
CHD Incidence Related to HDL-C
Levels in Various Trials
CHD incidence
Men
Women
0
-2
-4
-6
-8
-10
FHS
CPPT
LRCF
MRFIT
FHS
LRCF
95% confidence intervals (CIs) for adjusted
proportional hazards regression coefficients.
Gordon DJ et al. Circulation 1989;79:8–15
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
Gould AL et al. Circulation. 1998;97:946-952.
Major CHD Risk Factors Other Than
LDL-C According to NCEP ATP-III
Positive risk factors
Negative risk factor
• Age
• High HDL-C: 60
– male 45
mg/dL
– 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
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*
Group A
Uncomplicated HTN
Group B
HTN w/Risk Factors
Diabetes
High-normal
therapy‡
(130-139/85-89)
Lifestyle
Lifestyle
modification
modification
Stage 1
therapy
(140-159/90-99)
Lifestyle
Lifestyle
modification
(up to 12 mo)
modification†
(up to 6 mo)
Stages 2 and 3
therapy
(160/ 100)
Drug therapy
Drug therapy
JNC VI. November 1997:chapter 2. NIH publication 98-4080.
Group C
TOD/ CCD/
Drug
Drug
Drug
Probability of Death From CHD in Patients
With NIDDM and in Nondiabetic Patients,
With and Without Prior MI
100
Survival (%)
80
60
40
Nondiabetic subjects without prior MI
Diabetic subjects without prior MI
Nondiabetic subjects with prior MI
Diabetic subjects with prior MI
20
0
0
1
2
3
4 5
Years
6
7
Kaplan-Meier estimates
Haffner SM et al. N Engl J Med 1998;339:229–234
8
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
CHD death
• End of Year 1
years
HRT 116
Placebo 129
HRT 71
Placebo 58
CHD events (HRT) 42.5/1000 womenCHD events (Plac) 28/1000 women-
years
• Year 4-5:
years
CHD events (HRT) 23/1000 womenCHD events (Plac) 34.3/1000 women-
years
• DVT/PE
Cholelithiasis
JAMA 1998;280:605-613
HRT 6.3 vs. Plac 2.2
HRT 84 vs. Plac 62
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 lipidlowering drugs.
• Higher incidence of VTE and cholelithiasis in HRT group.
JAMA 1998;280:605-613
Is there clinical evidence that
inflammatory markers predict future
coronary events and provide additional
predictive information beyond traditional
risk factors?
hs-CRP and Risk of Future MI in Apparently
Healthy Men
P Trend
<0.001
3
Relative Risk of MI
P<
0.001
2
P<
0.001
P = 0.03
1
0
1
<0.055
2
3
4
0.056–
0.115–
>0.211
0.114
0.210
Quartile of hs-CRP (range, mg/dL)
Ridker PM et al. N Engl J Med 1997;336:973-979.
hs-CRP and Risk of Future Cardiovascular
Events in Apparently Healthy Women
P Trend
<0.002
7
Any Event
5
MI or Stroke
4
3
2
Relative Risk
6
1
0
1
<0.15
2
3
4
0.15–0.37 0.37–0.73
>0.73
Quartile of hs-CRP (range, mg/dL)
Ridker PM et al. Circulation 1998;98:731-733.
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
10
5
2
RR
2.7
1.9
1.8
1.8
1.2
1
0.5
Lp(a)
C HT
TC
GI
HDLSmoking
0.2
0.1
RR=relative risk; HT=hypertension; GI=glucose intolerance.
Bostom AG et al. JAMA. 1996;276:544-548.
3.6
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
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