Cardiovascular Disease: Risk Factors and Risk Assessment

Lifetime risk of CVD Lifetime risk of overall CVD approaches 50 percent for persons aged 30 years without known CVD Coronary heart disease (CHD) accounts for approximately one-third to one-half of the total cases of CVD

Framingham Heart Study The lifetime risk of CHD was illustrated in a study of 7733 participants, age 40 to 94, in the Framingham Heart Study who were initially free of CHD The lifetime risk for individuals at age 40 was 49% in men and 32% in women. Even those who were free from CHD at age 70 had a non-trivial lifetime risk of developing CHD (35 and 24% in men and women, respectively) Similar findings have been reported in a meta-analysis of 18 cohorts involving over 250,000 men and women

CVD Risk Despite increases in longevity and decreases in age-specific death rates from CVD, CHD, and stroke since 1975, CVD and its related complications remain highly prevalent and expensive to treat

CVD Risk While CVD remains the leading cause of death in most developed countries, mortality from acute MI appears to have decreased by as much as 50 percent in the 1990s and 2000s Many individuals in the general population have one or more risk factors for CHD, and over 90 percent of CHD events occur in individuals with at least one risk factor

CVD Risk The five leading modifiable risk factors are estimated to be responsible for more than half of cardiovascular mortality Hypercholesterolemia Diabetes Hypertension Obesity Smoking

Atherosclerosis is responsible for almost all cases of CHD Fatty streaks in adolescence Plaques in early adulthood Thrombotic occlusions and coronary events in middle age and later life

CVD Risk Factors Based upon the absolute, relative, and attributable risks imposed by the various risk factors, concepts of "normal" have evolved from usual or average to more optimal values associated with long-term freedom from disease. As a result, optimal blood pressure, blood glucose, and lipid values have been revised downward in the past 20 years

CVD Risk Factors a number of other major cardiovascular risk factors declined substantially between 1960 and 2000 Serum total cholesterol ≥240 mg/dL (6.2 mmol/L) – 34 to 17 percent Hypertension (blood pressure ≥140/≥90 mmHg) – 31 to 15 percent Smoking – 39 to 26 percent

CVD Risk Factors: Age and Gender  Cardiovascular risk factors promote CVD in either gender at all ages but with different relative importance Diabetes and a low high-density lipoprotein (HDL)-cholesterol/total cholesterol ratio operate with greater power in women The incidence of a myocardial infarction is increased six-fold in women and three-fold in men who smoke at least 20 cigarettes per day compared to subjects who never smoked

CVD Risk Factors: Age and Gender Systolic blood pressure and isolated systolic hypertension are major CHD risk factors at all ages and in both genders In patients <50 years of age, diastolic blood pressure was the strongest predictor of CHD risk in those 50 to 59 years of age, all three blood pressure indices were comparable predictors of CHD risk in those ≥60 years of age, pulse pressure was the strongest predictor

CVD Risk Factors: Age and Gender Obesity or weight gain promotes or aggravates all the atherogenic risk factors and physical inactivity worsens some of them, predisposing subjects of all ages to CHD events Age alone also appears to contribute to the development of CVD.

CVD Risk Factors: Family History Family history is an independent risk factor for CHD, particularly among younger individuals with a family history of premature disease there is general agreement that development of atherosclerotic CVD or death from CVD in a first degree relative (ie, parent or sibling) prior to age 55 (males) or 65 (females) denotes a significant family history The risk of developing CHD in the presence of a positive family history has ranged from 15 to 100 percent in various cohorts, with most cohorts showing a 40 to 60 percent increase.

CVD Risk Factors: Hypertension The lifetime risk of developing CVD is significantly higher among patients with hypertension The determination of what blood pressure constitutes hypertension has long been the subject of debate….. A separate issue is the goal blood pressure in patients who already have or are at high risk for cardiovascular disease.

What is normal blood pressure? Normal blood pressure: systolic <120 mmHg and diastolic <80 mmHg Prehypertension: systolic 120 to 139 mmHg or diastolic 80 to 89 mmHg Hypertension: Stage 1: systolic 140 to 159 mmHg or diastolic 90 to 99 mmHg Stage 2: systolic ≥160 mmHg or diastolic ≥100 mmHg

CVD Risk Factors: Lipids and Lipoproteins The following lipid and lipoprotein abnormalities are associated with increased CHD risk Elevated total cholesterol and elevated LDL-cholesterol Low HDL-cholesterol Hypertriglyceridemia Increased non-HDL-cholesterol Increased Lipoprotein (a) Increased apolipoprotein C-III Small, dense LDL particles Different genotypes of apolipoprotein E (apoE) influence cholesterol and triglyceride levels as well as the risk of CHD

CVD Risk Factors: Diabetes  Insulin resistance, hyperinsulinemia, and elevated blood glucose are associated with atherosclerotic cardiovascular disease In addition to the importance of diabetes as a risk factor, diabetics have a greater burden of other atherogenic risk factors than nondiabetics, including  hypertension, obesity, increased total-to-HDL-cholesterol ratio, hypertriglyceridemia, and elevated plasma fibrinogen. The CHD risk in diabetics varies widely with the intensity of these risk factors

CVD Risk Factors: Lifestyle Factors Cigarette smoking is an important and reversible risk factor for CHD Smoking is an independent major risk factor for total atherosclerotic CVD, CHD, cerebrovascular disease, and all-cause mortality, with an apparent dose-dependent relationship In the worldwide INTERHEART study of patients from 52 countries, smoking accounted for 36 percent of the population-attributable risk of a first MI Conversely, the risk of recurrent infarction in a study of smokers who had an MI fell by 50 percent within one year of smoking cessation and normalized to that of nonsmokers within two years The benefits of smoking cessation are seen regardless of how long or how much the patient has previously smoked

CVD Risk Factors: Lifestyle Factors Exercise — Exercise of even moderate degree has a protective effect against coronary heart disease and all-cause mortality Exercise may have a variety of beneficial effects including an elevation in serum HDL-cholesterol, a reduction in blood pressure, less insulin resistance, and weight loss. In addition to the amount of exercise performed, the degree of cardiovascular fitness (a measure of physical activity), as determined by duration of exercise and maximal oxygen uptake on a treadmill, is also associated with a reduction in coronary heart disease risk and overall cardiovascular mortality

CVD Risk Factors: Diet

CVD Risk Factors: Other considerations Psychosocial factors — Psychosocial factors may contribute to the early development of atherosclerosis as well as to the acute precipitation of myocardial infarction and sudden cardiac death. The link between psychologic stress and atherosclerosis may be both direct, via damage of the endothelium, and indirect, via aggravation of traditional risk factors such as smoking, hypertension, and lipid metabolism. Depression, anger, stress, and other factors have been correlated with cardiovascular outcomes

CVD Risk Factors: Other considerations Inflammatory markers — Numerous inflammatory markers have been reported to be associated with increased risk of CVD C-reactive protein (CRP) is both the most extensively studied marker of inflammation and the marker most widely used in clinical practice. Its precise role in the assessment of cardiovascular risk continues to evolve. While the precise role of CRP remains uncertain, epidemiologic studies have suggested that interleukin-6 (IL-6) has a direct causal role in the development of CHD

Risk Assessment of CVD Estimation of cardiovascular risk in an individual patient without known cardiovascular disease use of multivariate risk models Framingham risk score (1998) — The original Framingham risk score, published in 1998, was derived from a largely Caucasian population of European descent Subsequent studies have suggested that the Framingham risk score performs well for prediction of CHD events in black and white women and men

Framingham risk score (1998) Prediction variables used Endpoints assessed Age CHD death Gender Nonfatal MI Total or LDL cholesterol (mg/dL) Unstable angina HDL cholesterol (mg/dL) Stable angina Systolic blood pressure (mmHg) Diabetes mellitus (yes or no) Current smoking (yes or no)

Framingham risk score (2008) The original 1998 and revised 2002 Framingham risk scores do not include all of the potential manifestations and adverse consequences of atherosclerosis such as vascular complications

Framingham Risk Score 2008 Prediction variables used Endpoints assessed Age CHD death Gender Nonfatal MI Total cholesterol (mg/dL) Coronary insufficiency or angina HDL cholesterol (mg/dL) Fatal or nonfatal ischemic or hemorrhagic stroke Systolic blood pressure (mmHg) Transient ischemic attack Blood pressure treatment (yes or no) Intermittent claudication Diabetes mellitus (yes or no) HF Current smoking (yes or no)

ATP III hard CHD risk score (2002) Prediction variables used in ATP III hard CHD risk score (2002) Age Gender Total cholesterol (mg/dL) HDL cholesterol (mg/dL) Systolic blood pressure (mmHg) Blood pressure treatment (yes or no) Current smoking (yes or no)