Heart Disease in Women: New Concepts in Prevention and Management

Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program Division of Cardiology University of California, Irvine

Heart Disease The leading killer of women at all ages

So how long have we known that women are just not small men???

Cardiovascular Disease in Women

• 38.2 million women (34%) are living with cardiovascular disease and a much larger population is at risk.

• Heart disease and stroke are the no. 1 and no. 3 killers of women over age 25 • 1 in 30 die of breast cancer, but 1 in 2.5 die of cardiovascular disease or stroke.

• 66,000 more women than men die per year of cardiovascular disease; represents 54% of deaths in women compared to 46% in men.

AHA Heart Disease and Stroke Statistics 2004 Update, and Mosca et al., Circulation 2007; 115: 1481-1501.

CHD: Differences in Presentation and Findings in Women Compared to Men

–

Lower prevalence of MI

–

More severe CHF

–

More severe angina

–

Less angiographic CAD

–

More ostial lesions

–

More microvascular dysfunction?

–

Abnormal vasomotor tone?

–

More endothelial dysfunction?

Source:

Jacobs 2003

Diagnosis of Coronary Artery Disease in Women • Chest pain is experienced by most women with CHD, but non-chest pain presentations are more common in women than men • Other Presenting Symptoms

– Upper abdominal pain, fullness, burning sensation – Shortness of breath – Nausea – Neck, back, jaw pain • Associations – Precipitated by exertion – Precipitated by emotional distress

Source:

Charney 2002, Goldberg 1998

Women have smaller coronary

• After correcting for

arteries

body surface area, womens’ arteries are smaller • This can seriously affect symptoms from anything that reduces diameter – Stenosis – Endothelial dysfunction

Smaller arteries Endo thelium

Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594

Plaque Erosion and Outward (Positive) Remodeling

• Plaque erosion and Lumen

Plaque erosion

thrombus formation 2x likely in women (men have more plaque rupture) • Outward (positive) remodeling atherosclerotic lesion protrudes outward

Thrombus

than impinging on the

Formation

lumen Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594

Gender Differences in Atherosclerosis Women suffer more plaque erosions (above) compared to plaque explosions in men (below), leading to more acute coronary syndromes (unstable angina) and non-Q MI in women, making diagnosis more difficult and leading to delays in treatment.

NEJM 1999

NIH-NHLBI-sponsored Women’s Ischemia Syndrome Evaluation WISE • About 50% of women sent home with “normal coronaries” continue to experience disabling symptoms • Possibly d/t coronary microvascular or macrovascular endothelial dysfunction • 673/936 enrolled in WISE had persistent chest pain (PChP) • PChP-w no obstructive disease is not a benign condition – – 2x the number of CV events (MIs, strokes,CHF and CV deaths) than those w/o PChP.

Johnson,D, etal EurHeart Journal 2006

Assessing Ischemic Disease

• Stress EKG may be less useful in looking for ischemia – Guidelines still support for women with normal resting 12 lead EKG • Decreased functional capacity may predict poor outcomes – WISE showed that women who could not achieve 4.7 METS of work had a risk of death or nonfatal MI 3.7x higher that others with better functional capacity • Stress ECHO and SPECT are good options in women

Mortality Rates in Women

At Every Age, More Women Die From Heart Disease Than From Cancer

6500 4500 2500 1600 Coronary artery disease Stroke Lung cancer Breast cancer Colon cancer Endometrial cancer 1200 800 400

50% of women (1 in 2) will die from CVD compared with 4% (1 in 25) who will die from breast cancer

0 45 –49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 85+ Age (years)

National Center for Health Statistics. 1999:164-167.

• • • •

Women Experience

Menopause…..

Changes with Menopause Lipids

Total-Cholesterol HDL-Cholesterol   • • •

Prevalence Differences

Hypertension

Metabolic Syndrome

  • • •

Risk Factor, Disease, or Outcome Risk

– Triglycerides Diabetes Mellitus   Obesity (BMI >30)*** Waist Circumference >35”   ***

Obesity

~25% of women - BMI >30,

Less leisure-time physical activity

-

Greater functional decline

Adapted from Bellasi et al, New insights into ischemic heart disease in women. cleveland clinic journal of medicine; 74: 585-594

Menopause and the Risk of Coronary Heart Disease

(modified data from “Menopausal status as a risk for coronary artery disease” Arch Intern Med 1995;155:57-61

4 3.5

3 2.5

2 1.5

1 0.5

0 Before menopause After menopause 40 - 45 45 - 49 Age (in years) 50 - 54

Chest pain or Angina

Typical Angina:

heaviness, pressure or squeezing sensation behind the breastbone with radiation across the chest, up the neck or down the left arm or “strangling” or “suffocating” sensation. caused or worsened by exercise and eased by rest usually lasts two to five minutes

Atypical Angina (frequently encountered in women):

shortness of breath extreme fatigue lightheadedness or fainting nausea and/or indigestion

Women’s Early Warning Signs of a Heart Attack

• Weeks before Heart Attack (95% of women)  Unusual fatigue (70.7%)     Sleep disturbance (47.8%) Shortness of breath (42.1%) Indigestion (39.4%) Chest pain (29.7 %) • At time of Heart Attack     Shortness of breath (57.9%) Weakness (54.8%) Fatigue (42.9%) Chest pain (57%) McSweeney, JC et al. Circulation 2003; 2619-2623

Tracking women's awareness of heart disease: an American Heart Association national study Mosca L, et al.

Circulation. 2004 Feb 10;109(5):573-9 • Telephone survey of a nationally representative random sample of women; 1024 respondents age > or =25 years • 46% identified heart disease as the leading cause of death in women, up from 30% in 1997 and 34% in 2000 • Black, Hispanic, and younger women (<45 years old) had lower awareness of heart disease • Only 38% of women reported that their doctors had ever discussed heart disease with them.

Major Risk Factors

• Cigarette smoking (passive smoking?) • Elevated total or LDL-cholesterol • Hypertension (BP  140/90 mmHg or on antihypertensive medication) • Low HDL cholesterol (<40 mg/dL) † • Family history of premature CHD – CHD in male first degree relative <55 years – CHD in female first degree relative <65 years • Age (men  45 years; women  55 years) † HDL cholesterol  60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count.

Other Recognized Risk Factors

• Obesity: Body Mass Index (BMI) – Weight (kg)/height (m 2 ) – Weight (lb)/height (in 2 ) x 703 • Obesity BMI >30 kg/m 2 with overweight defined as 25-<30 kg/m 2 • Abdominal obesity involves waist circumference >40 in. in men, >35 in. in women • Physical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/week

BMI and Relative Risk of CHD Over 14 Years: Nurse’s Health Study

3.5

• Relative risk of CHD increases for BMI > 23,

2.5

diabetes risk increases

3 2

for BMI > 22.

1.5

• Risk also significantly increases for weight gain

0.5

after age 18 years of 5

1

kg or more.

0 <21 21-22.9 23-24.9 25-28.9

>29

Diabetes as a CHD Risk Equivalent

• 10-year risk for CHD  20% • High mortality with established CHD – High mortality with acute MI – High mortality post acute MI Prevalence has increased over 25% in past 15 years in California, paralleling 50% increase in overweight/obesity

Probability of Death From CHD in Patients With NIDDM and in Nondiabetic Patients, With and Without Prior MI 100 80 60 40 20 Nondiabetic subjects without prior MI Diabetic subjects without prior MI Nondiabetic subjects with prior MI Diabetic subjects with prior MI 0 0 1 2 3 4 Years 5 Kaplan-Meier estimates Haffner SM et al. N Engl J Med 1998;339:229–234 6 7 8

Framingham Heart Study 30-Year Follow-Up: CVD Events in Patients With Diabetes (Ages 35-64)

10 10 9 Men Women 8 11 Risk ratio 6 30 19 4 38 9 6 20 3* 2 0 Total CVD CHD Cardiac failure Intermittent claudication Age-adjusted annual rate/1,000 Stroke

P

<0.001 for all values except *

P

<0.05.

Wilson PWF, Kannel WB. In:

Hyperglycemia, Diabetes and Vascular Disease.

Ruderman N et al, eds. Oxford; 1992.

Primary and Secondary Prevention Trials With Statins

1 ° prevention statin 1 ° prevention placebo 2 ° prevention statin 2 ° prevention placebo

30 25 20 15 10 5 0 80 HPS

CARE LIPID

90

AFCAPS 4S

HPS

CARE AFCAPS LIPID WOSCOPS

LDL-C Achieved (mg/dL)

4S WOSCOPS

100 110 120 130 140 150 160 170 180 190 200

Adapted from Ballantyne CM.

Am J Cardiol.

1998;82:3Q-12Q .

CHD Events: Results of Secondary Prevention Studies in Women

Placebo No.

Events/Women Intervention No.

Events/Women RR (95% CI)

4S 91/420 60/407 0.68 (0.51-0.91) CARE LIPID HPS Total and summary 80/290 104/760 282/1638 557/3108 46/286 90/756 237/1628 433/3077 0.60 (0.37-0.97) 0.87 (0.67-1.13) 0.85 (0.72-0.99) 0.80 (0.71-0.91) 0 1 2 P value for heterogeneity=.35

Walsh et al. JAMA . 2004;291:2243-2252.

Testing for Ischemic Heart Disease in Women and Factors to Consider

Technique Assessment Issues in Women

Angiography Coronary CT Echocardiograp hy Nuclear Cardiology Coronary anatomy Coronary calcification Less focal disease Less well-validated than other techniques Regional wall motion Regional blood flow Reader expertise variable Attenuation issues

Source:

Charney 2002, Greenland 2007

Drawbacks of Diagnostic Imaging in Women

• Low exercise capacity – adequate pressure rate product – Solution: Pharmacologic stress testing • Breast attenuation artifact – higher false positive imaging studies for nuclear imaging positive rate into  likelihood of reaching – Solution: Gated acquisition; attenuation correction – Solution: Echocardiography • Lower pretest probability of CAD – higher false – Solution: Integrate clinical variables, risk factors, decision-making process

Source:

Duvernoy, personal communication

Women and CHD: What Test to Order When

• For women at high or intermediate risk of coronary artery disease, consider treadmill echocardiogarphy or nuclear perfusion imaging • For women unable to exercise, consider dobutamine stress echocardiography or adenosine or dipyridamole nuclear imaging • In high risk women with typical symptoms of coronary artery disease, consider referral to a cardiologist • For high risk women, consider cardiac catheterization if symptoms persist despite negative non-invasive imaging

Source:

Anderson 2007, Klocke 2003, Douglas 2008, Duvernoy 2005

Women and CHD: What Test to Order When

• A stepwise approach beginning with conventional exercise testing may be considered for women who: – Are at low or intermediate risk for coronary artery disease – Are able to exercise – Have an electrocardiogram that can be interpreted during stress testing • An image-enhanced test may be more predictive in women than conventional electrocardiogram stress testing, and may also be more cost effective in women at intermediate risk for CHD

Source:

Anderson 2007, Klocke 2003, Douglas 2008,Mieres 2005

Mosca L et al.

Circulation

. 2004;109:672-693 and Circulation 2007; 115: 1481-1501.

• • • • •

Say

ALOHA

to Heart Disease in Women

A

– Assess your risk: high, intermediate, or low?

L

– Lifestyle recommendations are first priority

O

– Other interventions prioritized according to expert panel rating scale

H

– Highest priority for therapy is for women at highest risk

A

– Avoid medical therapies called Class III where evidence is lacking Mosca L. Circulation 2004

A - Assessment of CHD Risk

For persons without known CHD, other forms of atherosclerotic disease, or diabetes:

• Count the number of risk factors.

• Use Framingham scoring if  2 risk factors* to determine the absolute 10-year CHD risk.

• Determine risk status: high (>20% 10-year risk or CHD risk equivalents), intermediate (10-20% 10 year risk), or low (<10% risk) *For persons with 0 –1 risk factor, Framingham calculations are not necessary. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.

JAMA

. 2001;285:2486-2497.

© 2001, Professional Postgraduate Services ® www.lipidhealth.org

ATP III Framingham Risk Scoring

Assessing CHD Risk in Women

Step 1: Age Step 4: Systolic Blood Pressure Step 6: Adding Up the Points Years Points 20-34 -7 Systolic BP (mm Hg) Points Points if Untreated if Treated 35-39 -3 Age Total cholesterol <120 0 0 40-44 0 HDL-cholesterol 120-129 1 3 45-49 3 Systolic blood pressure 130-139 2 4 50-54 6 Smoking status 55-59 8 140-159



160 3 5 60-64 10 4 6 Point total 65-69 70-74 75-79 12 14 16 Step 7: CHD Risk Point Total 10-Year Risk Point Total 10-Year Risk Step 2: Total Cholesterol TC at Points at (mg/dL) 70-79 <160 160-199 200-239 240-279



280 HDL-C (mg/dL)



60 Points at 0 4 8 11 13 Points -1 Points at 0 3 6 8 10 Points at 0 2 4 5 7 Points Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 0 1 2 3 4 0 1 1 2 2 <9 9 10 11 12 13 14 15 16 17 18 19 <1% 1% 1% 1% 1% 2% 2% 3% 4% 5% 6% 8% 20 21 22 23 24



25 11% 14% 17% 22% 27%



30% 50-59 0 Step 5: Smoking Status Nonsmoker Smoker 0 9 40-49 1 0 7 0 4 0 2 0 1 <40 2

Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA.

© 2001, Professional Postgraduate Services ® www.lipidhealth.org

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.

JAMA

. 2001;285:2486-2497.

A Assessment of CHD Risk

Classification of CVD Risk in Women (Mosca et al., Circ 2007) • High Risk: – Established coronary heart disease – Cerebrovascular disease – Peripheral arterial disease – Abdominal aortic aneurysm – End-stage or chronic renal disease – Diabetes mellitus – 10-year Framingham global risk >20%

Classification of CVD Risk in Women (Mosca et al., Circ 2007) • At Risk : – Evidence of subclinical vascular disease (e.g., coronary calcium) – Metabolic Syndrome – Poor exercise capacity on treadmill and/or abnormal heart rate recovery – >=1 major risk factor for CVD including: • Cigarette smoking • Poor diet • Physical inactivity • Obesity (esp central obesity) • Family history of premature CVD (<55 male or <65 female relative) • Hypertension • Dyslipidemia • Optimal risk: Framingham global risk <10% and a healthy lifestyle with no risk factors

Priorities for Prevention in Practice According to Risk Assessment Class I recommendations High-Risk Women (>20% Risk) Smoking cessation Phys activity/card rehab Diet therapy Weight maint/reduct BP control Cholest control/Rx Aspirin therapy -Blocker therapy ACE inhibitor (ARBs) Mgmt/control of DM Intermediate-Risk Women (10% to 20% Risk) Smoking cessation Physical activity Heart-healthy diet Weight maint/reduct BP control Cholesterol control Lower-Risk Women (10% Risk) Smoking cessation Physical activity Heart-healthy diet Weight maint/reduct Treat individual heart risk factors as indicated Class IIa recommendation Class IIb recommendations Treatment for depression Omega 3 fatty-acid supplementation Folic acid supplementation Aspirin therapy

Mosca, L “Heart Disease Prevention in Women” Circulation, 2004

L – Lifestyle Change: First Line of Defense Against Heart Disease • The AHA expert panel rated the following as Class I recommendations: – Stop cigarette smoking and avoid secondhand tobacco smoke – Get at least 30 minutes of physical activity most or preferably all days (60-90 minutes for those needing to lose or sustain weight) – Start a risk-reduction or cardiac rehabilitation program if recent acute coronary syndrome or cardiovascular event – Eat a heart-healthy diet (consistent with NCEP/ATP III TLC) – Maintain healthy weight by balancing caloric intake with caloric expenditure to achieve BMI between 18.5-24.9 kg/m 2 Mosca et al. Circulation 2004 and 2007

• • • • • • •

Essential Components of NCEP Therapeutic Lifestyle Change (TLC)

Decrease in saturated fats (<7% of total calories) and trans fatty acids 1 Increased dietary and supplemental fiber 1

–

High-fiber breakfast cereals, supplements, and so forth Plant sterols and stanols (2 g/d) 1

–

Spreads, pills, added to yogurt or other foods, or combined with aspirin Soy protein 2 Flavonoids (nuts) 3 Weight loss 1 Exercise 1 1.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.

JAMA.

2001;285(19):2486-2497.

• 2.

Sacks FM, et al; American Heart Association Nutrition Committee.

Circulation

. 2006;113(7):1034-1044.

• 3.

Kelly JH Jr and Sabaté J.

Br J Nutr

. 2006;96(suppl 2):S61-S67.

Aspirin in Primary Prevention: Effective Gender Differences

RR of MI Among Men RR of Stroke Among Men BDT, 1988 PHS, 1989 TPT, 1998 HOT, 1998 PPP, 2001 Combined 0.2

0.5

1.0

RR = 0.68 (0.54

–0.86) P = .001

2.0

RR of MI Among Women 5.0

HOT, 1998 PPP, 2001 WHS, 2005 Combined 0.2

0.5

Aspirin Better RR = 0.99 (0.83

–1.19) P = .95

1.0

2.0

Placebo Better 5.0

0.2

0.5

1.0

RR = 1.13 (0.96

–1.33) P = .15

2.0

RR of Stroke Among Women 5.0

RR = 0.81 (0.69

–0.96) P = .01

0.2

0.5

Aspirin Better 1.0

2.0

Placebo Better 5.0

Ridker, P. et al.,

N Engl J Med

2005; 352:1293-204.

Blood Pressure Regulation in Women

• 3 of every 4 women with high blood pressure know they have it • Fewer than 1 in 3 are controlling it • All women must take steps to control their high blood pressure NIH Web site. Your guide to lowering high blood pressure: issues for women.

Available at: http://www.nhlbi.nih.gov/hbp/issues/issues.htm.

AHA Guidelines for CVD Prevention in Women: Blood Pressure

• Encourage an optimal blood pressure of <120/80 mm Hg through lifestyle approaches (Class I, Level B) • Pharmacotherapy when BP is –  140/90 mm Hg • Get BP even lower when – –

Target-organ damage Diabetes

(Class I, Level A) Mosca L et al.

J Am Coll Cardiol

. 2004;43:900-921.

CHD Risk Equivalents

• > 20% 10-year risk of CHD (Framingham projections) (downloadable risk algorithms at www.nhlbi.nih.gov) • Diabetes • Other forms of clinical atherosclerotic disease – Peripheral arterial disease (ABI <0.90) – Abdominal aortic aneurysm – Carotid artery disease (>=1mm CIMT?) NCEP ATP III. JAMA. 2001;285:2486-2497.

Other Modalities for Measuring Atherosclerotic Burden

• Carotid B-mode ultrasonography: intimal medial thicknesses • Ankle-Brachial Index (ABI) for assessment of peripheral vascular disease • CT (EBT or multislice detectors): coronary calcium score or volume • Magnetic resonance imaging of carotid plaques: vessel wall area • Intravascular ultrasound (invasive)

Recommendations for Noninvasive Screening

• AHA Prevention V (Greenland et al., Circ. 2000) indicated persons at intermediate risk may be suitable for screening by noninvasive tests, including ABI and carotid US for those over age 50 years, and coronary calcium screening.

• ATP III has suggested CAC scores above 75 th percentile indications for more aggressive treatment (e.g., as CHD risk equivalent).

Cardiovascular Health Study: Combined intimal-medial thickness predicts total MI and stroke

Cardiovascular Health Study (CHS) (aged 65+): MI or stroke rate 25% over 7 years in those at highest quintile of combined IMT (O’Leary et al. 1999)

Significant Coronary Artery Calcium (Score >400)

Risk of Total Mortality by Calcium Category in 10,377 Asymptomatic Individuals Shaw LJ et al., Radiology 2003; 228: 826-33

L – Lifestyle Change: First Line of Defense Against Heart Disease

• The AHA expert panel rated the following as Class I recommendations: – Stop cigarette smoking and avoid secondhand tobacco smoke – Get at least 30 minutes of physical activity each day – Start a cardiac rehabilitation program if recently hospitalized for heart disease – Eat a heart-healthy diet – Maintain healthy weight by balancing caloric intake with caloric expenditure Mosca et al. Circulation 2004

ATP III: Nutritional Components of the TLC Diet

Nutrient

Saturated fat* Polyunsaturated fat Monounsaturated fat Total fat Carbohydrate (esp. complex carbs)

Recommended Intake

<7% of total calories Up to 10% of total calories Up to 20% of total calories 25%–35% of total calories 50%–60% of total calories Fiber Protein Cholesterol 20–30 g/d ~15% of total calories <200 mg/d *Trans fatty acids also raise LDL-C and should be kept at a low intake.

Note: Regarding total calories, balance energy intake and maintain desirable body weight.

. 2001;285:2486-2497.

© 2001, Professional Postgraduate Services ® www.lipidhealth.org

Possible Benefits From Other Therapies

Therapy Result

• Soluble fiber in diet (2–8 g/d) (oat bran, fruit, and vegetables)  LDL-C 1% to 10% • Soy protein (20–30 g/d) • Stanol esters (1.5–4 g/d) (inhibit cholesterol absorption)  LDL-C 5% to 7%  LDL-C 10% to 15% • Fish oils (3–9 g/d) (n-3 fatty acids)  Triglycerides 25% to 35% Jones PJ.

Curr Atheroscler Rep.

1999;1:230-235.

Lichtenstein AH.

Curr Atheroscler Rep.

1999;1:210-214.

Rambjor GS et al.

Lipids.

1996;31:S45-S49.

Ripsin CM et al.

JAMA.

1992;267:3317-3325.

Nuts, Soy, Phytosterols, Garlic

• Nurses’ Health Study: five 1oz servings of nuts per week associated with 40% lower risk of CHD events; 2-4 servings/wk 25% lower risk • Metaanalysis of 38 trials of soy protein showed 47g intake lowered total, LDL-C, and trigs 9%, 13%, and 11%, respectively; no effect on HDL-C.

• Phytosterol-supplemented foods (e.g., stanol ester margarine) lowers LDL-C avg. 10% • Meta-analysis of garlic studies showed 9% total cholesterol reduction from 1/2-1 clove consumed daily for 6 months.

Health Benefits of Weight Loss

• • • •

Decreased cardiovascular risk Decreased glucose and insulin levels Decreased blood pressure Decreased LDL and triglycerides, increased HDL

• •

Decrease in severity of sleep apnea Reduced symptoms of degenerative joint disease

•

Improved gynecological conditions

1

Patient Encounter

2

National Obesity Education Initiative Treatment

No 3

BMI measured in past 2 years?

4

• Measure weight, height, and waist circumference • Calculate BMI

Yes 6 5

waist circumference > 88 cm (F) > 102 cm (M)

Yes

Assess risk factors

No 14 Yes

Examination Treatment

No 15 13

Brief reinforcement/ educate on weight management Advise to maintain weight/address other risk factors

16

Periodic weight check

:

Algorithm

7

BMI



30 OR {[BMI 25 to 29.9

Yes

>88 cm (F) >102 cm (M)]



factors}

No 12

Does patient want to lose weight?

Yes No 8

Clinician and patient devise goals and treatment strategy for weight loss and risk factor control

Yes 9

Progress being made/goal achieved?

No 11

Dietary therapy Behavior therapy Physical activity

10

Assess reasons for failure to lose weight

Weight Loss Therapy

Whenever possible, weight loss therapy should employ the combination of • Low-calorie/low-fat diets • Increased physical activity • Behavior modification

O – Other Interventions with Class I Recommendations

• Blood pressure – encourage optimal levels of <120/80 mmHg • Cholesterol levels – optimal cholesterol levels <200 mg/dl, LDL-C< 100 mg/dl, HDL >50 mg/dl, triglycerides <150 mg/dl • Diabetes – recommend control to HgbA1c < 7%

Evidence-based Guidelines for CVD Prevention in Women – Major Risk Factor Interventions (Mosca et al., Arterioscler Throm Vasc Biol 2004; 24: e29-e50)

I have some bad news for you. While your cholesterol has remained the same, the research findings have changed.

When LDL-lowering drug therapy is employed in high-risk or moderately high risk patients, intensity of therapy should be sufficient to achieve a 30–40% reduction in LDL-C levels.

JNC-7 New Features and Key Messages

 Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes.  Certain high-risk conditions are compelling indications for other drug classes.

 Most patients will require two or more antihypertensive drugs to achieve goal BP.

 If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.

H – Highest Priority for Therapy is for Women at Highest Risk

• Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations: – ACE inhibitor therapy (if coughing, subst. ARB) – Aspirin therapy (baby aspirin or maximum dose of 162 mg) unless contraindicated – Beta-blocker therapy in those with prior MI or current angina – Statin therapy – Niacin or fibrate therapy if low HDL present – Fibrates to lower triglycerides and improve HDL – Warfarin in those with atrial fibrillation unless contradindicated

H – Highest Priority for Therapy is for Women at Highest Risk

• Those at highest risk, who already have pre-existing CVD, diabetes, or chronic kidney disease are most likely to benefit from preventive therapy involving the following Class I recommendations: – ACE inhibitor therapy (if coughing, subst. ARB) – Aspirin therapy (baby aspirin or maximum dose of 162 mg) unless contraindicated – Beta-blocker therapy in those with prior MI or current angina – Statin therapy – Niacin or fibrate therapy if low HDL present – Fibrates to lower triglycerides and improve HDL – Warfarin in those with atrial fibrillation unless contradindicated

A – Avoid “Class III” Interventions

(Not proven useful or effective / may be harmful) • Combined estrogen and progestin therapy, and *estrogen monotherapy since associated with increased risk of CVD • Selective estrogen-receptor modulators (SERMs) also not recommended • Antioxidant supplements including vigtamin E, C, and beta carotene • Folic acid with or without B6 or B12 supplementation • Aspirin for MI prevention in women aged <65 years

Vitamins: Major Vascular Events

Vascular Event

Major coronary

Vitamins (n = 10,269) Placebo (n = 10,267)

1063 1047

Risk Ratio and 95% CI Vitamin Better Vitamin Worse

Any stroke Revascularization Any of the above 511 1058 2306 (22.5%) 518 1086 2312 (22.5%) 1.00 (0.94

–1.06)

P

> 0.9

0.4 0.6 0.8 1.0 1.2 1.4

Heart Protection Study Collaborative Group.

Lancet.

2002;360:23 –33.

Does Hormone Replacement Therapy Prevent Heart Disease?

• Epidemiologic studies over the past several decades together have shown approximately a 50% lower risk in women randomized to estrogen replacement therapy vs. placebo • Even the Nurses’ Health Study showed those on estrogen/progestin to have approximately a 60% lower risk of heart disease events

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

• 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.

JAMA 1998;280:605-613

More Bad News: The Women’s Health Initiative

• Over 160,000 women nationwide, aged 50-79 and postmenopausal have participated in various components (observational, dietary modification, and HRT clinical trials)—over 3,000 at UCI • The Estrogen/Progestin component of the HRT clinical trial involving 16,608 women nationwide was discontinued prematurely in Spring 2002 after 5.2 years of follow-up (instead of 8.5 years).

WHI Estrogen/Progestin and Estrogen Only Results

• Those randomized to estrogen/progestin compared to placebo and statistically significant increased risks: – Breast cancer 26% (8/10,000 person years) – Total coronary heart disease 29% (7/10,000 person years) – Stroke 41% (8/10,000 person years) – Pulmonary emobolism 2.1 X (8/10,000 person years) – Protective for colorectal cancer (37% lower) and hip fracture (34% lower): no effect endometrial cancer or total mortality JAMA. 2002 Jul 17;288(3):321-33. • Estrogen-only arm was also recently discontinued in December 2003 and was associated with a 39% increased risk of stroke (12 excess strokes per 10,000 person years) and 12% significant increased risk of cardiovascular events. JAMA. 2004 Apr 14;291(14):1701-12.

Women Making a Change

For More Information about Preventing Heart Disease:

Preventive Cardiology, 2

nd

ed.

from McGraw-Hill …..

For more information, see the UCI Heart Disease Prevention Website at www.heart.uci.edu