Cardiovascular Disease

D. Bellis McCafferty

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Cardiovascular Disease – general term that means diseases of the heart and blood vessels– Coronary Heart Disease (CHD) – AKA

Coronary Artery Disease and Ischemic Heart Disease – lack of blood flow to the network of blood vessels surrounding (and serving) the heart. The major cause is atherosclerosis.

– Ischemia – insufficient blood flow in a tissue due to functional constriction or actual obstruction of a blood vessel.

– Atherosclerosis – thickening and hardening of the walls of the blood vessels caused by deposits of fatty material. Arteries most often affected are the abdominal aorta, coronary and carotid arteries.

– Myocardial Infarction (MI) – Ischemia in the coronary arteries resulting in necrosis, tissue damage and sometimes sudden death.

– Cerebrovascular Accident (CVA) – event in which the blood flow to a part of the brain is cut off.

– Transient Ischemic attack (TIA) – temporary reduction in cerebral blood flow that causes temporary symptoms that mimic those of a CVA.

Atherosclerosis

Pathogenesis: “Response to Injury” theory

1. Formation of fatty streaks along arterial walls

2. Proliferation of smooth muscle cells, WBC and calcium plaques.– Plaques cause the arteries to lose

elasticity– Narrowing of arterial lumen– (Most people have well-developed

plaques by age 30)

Consequences

1. Loss of elasticity injury to arterial wall

2. Platelet aggregation and blood clotting (response to injury)– Thrombosis: blood clot obstructs blood

flow, causing tissue death– Embolism: clot breaks off and travels to

smaller vessel and obstructs blood flow, causing tissue death.

– Angina: pain, pressure, and tightness in chest, back, neck, and arms, caused by lack of O2 to heart muscle

3. Hypertension (more pressure required to deliver blood to tissues if arteries are narrowed)– Further damage to blood vessels

more clots, etc.

Dietary Treatment of High Blood Cholesterol in Adults

NCEP’s updated clinical guidelines for cholesterol testing and management: ATP III(Adult Treatment Panel III)

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3xsum.pdf

“These guidelines are intended to inform, not replace, the physician’s clinical judgment, which must ultimately determine the appropriate treatment for each individual.”

Focus: Lowering LDL cholesterol (major cause of CHD, and LDL-lowering therapy reduces risk for CHD)

Major new feature: focus on primary prevention in persons with multiple risk factors. 

New recommendation: All adults aged 20 yrs or older should obtain a fasting LP profile every 5 years (TC, HDL, LDL, TG).

Blood Lipid Levels• Total cholesterol (adults)

– desirable < 200 mg/dl

– borderline high 200-239 mg/dl– high risk 240 mg/dl

• LDL cholesterol – optimal <100 mg/dl (goal if CVD, DM or

multiple RF’s*)– Above optimal 100-129 mg/dl – borderline high 130-159 mg/dl (<130 goal if 2+ RF’s**)– high risk >160 mg/dl (<160 goal if 0-1 RF)

• HDL cholesterol 40 mg/dl (60: neg. risk factor)

• Triglycerides (TG) 150 mg/dl (requires tx beyond LDL lowering if >200)

To convert mmol/l of HDL or LDL cholesterol to mg/dl, multiply by 39.

To convert mg/dl of HDL or LDL cholesterol to mmol/l, divide by 39.

To convert mmol/l of triglycerides to mg/dl, multiply by 89.

To convert mg/dl of triglycerides to mmol/l, divide by 89.

Risk FactorsRF’s that modify LDL Goals: blue

• Category I risk factors: – Intervention has been proven to decrease CVD risk

• Category II risk factors: – Intervention is likely to decrease CVD risk

• Category III risk factors:– Intervention may decrease risk

• Category IV risk factors:– Intervention does not decrease risk

Category I Risk Factors

1. Cigarette smoking

– Doubles CVD risk– Synergistic w/other risk factors HDL, VLDL and BG levels

2. LDL Cholesterol sat’d fat intake cholesterol intake in some people trans FA intake– obesity

3. Hypertension Risk for stroke, CHD, and CHF– 140/90 mm Hg– Risk : AA, age, obesity

Category II Risk Factors1. Diabetes

– LDL chol goal for people w/DM is 100 mg/dl

2. Physical Inactivity– Sedentary people (60% of US) have double the

risk of developing CVD as active people.– Modifies other risk factors

3. HDL cholesterol <40 mg/dl– Greater effect than LDL?– Reverse cholesterol transport– Increased with: EXERCISE, estrogen

replacement, loss of body fat, moderate consumption of alcohol

4. Obesity– BMI ranges– Affects glu tolerance, blood lipids, BP, etc.– Body fat distribution

Category III Risk Factors1. Psychosocial Factors

– Correlated w/risk, but intervention is not strongly correlated with decreased risk.

– Type “A” personality, stress, depression– Low education level

2. Triglycerides– Inversely correlated w/HDL– Increased with: high CHO, low fat, vegetarian

diet, obesity, uncontrolled DM, excessive EtOH (and factors that decrease HDLs)

3. Lp(a): Early studies indicated strong correlation w/CHD risk– Conflicting evidence

4. Homocysteine– Strong + correlation w/premature ds. with inadequate folate, B6 and B12– Also smoking, inactivity, coffee (>1c/day)

5. Oxidative stress*– LDL damage– Inhibited* by vits C, E, b-carotene, mufa’s w/Iron, copper, zinc, and sat’d fat*no conclusive evidence (randomized trials) that

supplemental antioxidants reduce disease risk - food vs. supplements

6. Alcohol consumption - moderate

Category IV Risk Factors1. Age Male gender and over 45 y/o Female gender and over 55 y/o2. Family history

MI <age 55 in a male first degree relativeMI <age 65 in a female first degree relative

(familial dyslipidemias)

Therapeutic Lifestyle Changes (TLC)

• Reduced intakes of saturated fats (<7% of total calories) and

• Cholesterol (<200 mg per day) • Therapeutic options for enhancing LDL lowering

such as plant stanols/sterols (2 g/day) and increased viscous (soluble) fiber (10-25 g/day)

• Weight reduction• Increased physical activity

Nutrient Composition of the TLC Diet

Nutrient

Saturated fat*

Polyunsaturated fat

Monounsaturated fat

Total fat

Carbohydrate†

Fiber

Protein

Cholesterol

Total calories (energy)‡

Recommended Intake

Less than 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

20-30 g/day

Approximately 15% of total calories

Less than 200 mg/day

Balance energy intake and expenditure to maintain desirable body weight/prevent weight gain

Drugs Affecting Lipoprotein Metabolism• HMG CoA reductase inhibitors (statins)

HDL (5-15%) LDL (18-55%) TG (7-30%)– Lovastatin, atorvastatin (Lipitor), simvstatin, etc.

• Bile acid sequestrants hepatic synthesis of cholesterol HDL (3-5%) LDL (15-30%)– Cholestyrmaine

• Nicotinic acid hepatic VLDL synthesis and thus LDL formation LDL (5-25%) TG (20-50%)

• Fibric Acids – Several mechanisms of action HDL (10-20%) LDL (5-20%) TG (20-50%)– Gemfibrozil

Metabolic Syndrome• Cluster of risk factors that enhance risk for CHD at any

given LDL cholesterol level.• Diagnosis: 3 or more of the following risk determinants:

Risk FactorAbdominal Obesity*

MenWomen

TriglyceridesHDL cholesterol

MenWomen

Blood pressureFasting glucose

Defining Level

Waist Circumference†>102 cm (>40 in)>88 cm (>35 in)

³150 mg/dL

<40 mg/dL<50 mg/dL

³130/³85 mmHg

³110 mg/dL

• Treatment of Metabolic Syndrome:

– Treat/reduce underlying causes

– TLC Diet: a higher intake of total fat (mostly unsaturated) can help TG and HDL cholesterol in persons w/Metabolic Syndrome

– Weight control

– Physical activity

– Plant stanols/sterols

– Viscous (soluble) fiber

Other Strategies folate, B6, B12 ( Homocysteine) w-3 FAs ( TG and VLDL, platelet

aggregation/clotting, BP) soluble fiber intake intake of soy products

– approved health claim, must have over 6 gram per serving to make claim

– 25 g/day will lower LDL-cholesterol levels by about 5-12%

• Plant Sterols/Stanols– Naturally present in vegetable oils, nuts,

cereals, beans – “Benecol” margarine produced by Finnish

company/”Take Control”– Sterols/stanols interfere with dietary and biliary

cholesterol absorption TC, LDL

– May complement statin therapy• Alcohol

• CABG: Coronary Artery Bypass Graft: vein from leg or artery from chest is used to alter blood flow around a diseased vessel. New vessels are still subject to atherosclerosis.

• Carotid endarterectomy: surgical removal of plaque in carotid artery to prevent stroke.

• Coronary Angioplasty: balloon catheter is inserted through an artery in the groin and is guided into the narrowed coronary artery. The balloon is inflated and compresses plaque back onto the arterial wall to allow better blood flow. Restenosis of artery is common.

• Holistic treatment: – Dean Ornish’s program shown to

reverse atherosclerotic plaque. Radical: includes extremely lowfat/low chol. diet (10-15% fat, 5mg cholesterol, vegetarian) in conjunction with conventional treatment, exercise, stress management, smoking cessation. His studies showed pts had less plaque after 1 year (via angiogram) and had lower BP and lipid levels.

Congestive Heart Failure

• Congestive Heart Failure (CHF)– heart loses ability to provide adequate blood

flow to the rest of the body– tries to compensate by increasing in size,

increasing force of contraction, increasing HR– reduced blood flow to kidneys stimulates

kidneys to conserve Na and H2O– As heart fails, blood begins to pool in the

pulmonary veins and capillaries pulmonary edema (ergo “congestion”)

• Cardiac Cachexia: Chronic PEM 2heart disease nutrient needs 2 work of heart

and lungs– Poor delivery of nutrients/oxygen to

tissues– Repeated respiratory infections– Anorexia, nausea, altered taste,

physical exhaustion– Edema may mask weight loss until

severe– PEM weakening of heart/lungs;

infections

• Nutrition Therapy: Don’t overfeed! – Increases cardiac workload– Safe rate of weight loss if indicated

(not if PEM, of course)– Sodium restriction proportionate to

fluid retention– Fiber: avoid constipation; straining

increases cardiac work

HypertensionNew Blood Pressure Cutoffs (2003)

Normal: <120/<80 mm Hg

Prehypertension: 120-139/80-89 mm Hg

Stage 1 hypertension: 140-159/90-99 mm Hg

Stage 2 hypertension: >160/>100 mm Hg

• Essential or Primary Hypertension:– No identifiable cause

• Secondary Hypertension: – Due to underlying disease such as kidney

disease

• White-coat Hypertension: – Caused by anxiety in a hospital setting.

Spanish study reports as many as 2 in 5 diagnoses!

Consequences

• CHF

• Kidney disease

• Peripheral vascular disease

• Stroke

• Impaired vision/blindness

Risk Factors for HypertensionUncontrollable

1. Age

2. Heredity

African Americans: 4x death rate vs. whites

3. Family history

Risk FactorsControllable/Modifiable

1. Overweight/Obesity2. Smoking3. Excessive EtOH4. Sodium intake

2400mg = 6g (1tsp) table salt5. Other minerals: Adequate K+ does lower blood pressure.

Inadequate data that Ca and Mg supplementsI prevent HTN.K+: fruits, vegetables, dairy foods, and fish.

Prevention/Treatment of Hypertension

1. Follow a healthy eating pattern

DASH diet

Dietary

Approaches to

Stop

Hypertension

• DASH: Dietary Approaches to Stop Hypertension– Diet high in fruits, vegetables, and nonfat dairy– Low in fat, saturated fat, and cholesterol

• Sodium• Potassium• (Calcium and Magnesium)• Alcohol• Exercise• Obesity/Weight Management

1st DASH study

• 133 subjects with mild hypertension• 326 subjects with normal blood pressure• 8 week study

1) control diet: average levels of fat/cholesterol; below average levels of K, Ca, Mg

2) fruit and vegetable diet: same as control diet but had 8-10 servings of fruit/veges (hi in K, Mg and fiber)

3) combination diet: Cut fat and cholesterol, high fruit/vege, high in low-fat dairy (Ca-rich)

Results

• Lowest blood pressure on DASH diet

2nd DASH sodium Trial

• 412 subjects (120-159/80-95)

• 2 weeks of typical American high-Na diet then 30 day intervention

• Then typical diet or DASH diet with

1) 3300 mg Na

2) 2400 mg Na

3) 1500 mg Na

Findings

• Lower sodium correlated with lower blood pressure

• Best results: DASH diet with 1500 mg Na+

2. Exercise

• Several studies show exercise lowers blood pressure (by about 10 mmHg)

• How?

How? Not clear but may

- peripheral resistance

- serum catecholamine ( SNS

response)

- renin activity (renin activates

angiotensin/aldosterone - Na

retention)

- central fat (?)/ insulin levels

Guidelines for Exercise

Stage 1 Hypertension:

• 50-85% of VO2 max for 20-60 minutes

3-5 days per week

Stage 2 Hypertension:

• 40-70% of VO2 max for 20-60 minutes

3-5 days per week

Resistance Exercise:

• Mild to moderate is OK (30-60% of maximal effort)

Drugs

• Diuretics

• beta-blockers– (atenolol, metoprolol, propranolol) act as

competitive antagonists at the adrenergic beta receptors