Epidemiology of Chronic Coronary Artery Disease

Sources of Epidemiologic Data

Participants in observational studies are not necessarily under the care of clinicians, and generalizing research study or survey findings to clinical care should be undertaken with caution. For example, the observations in a report may be compiled over many years, the diagnosis may be self-reported or based on field survey methods, and it may be difficult to compare results across studies because of differences in methods. In addition, interpretation of the efficacy of treatments in observational studies can be difficult. Behavioral interventions and medications may be identified, but it can be difficult to be sure that the individual actually complied with what was prescribed or recommended.

Prevalence of Coronary Artery Disease

The 2016 Heart Disease and Stroke Statistics update of the American Heart Association (AHA) reports that 15.5 million adults (6.2% of the adult population) in the United States have CAD, including 7.6 million (2.8%) with MI and 8.2 million (3.3%) with angina pectoris. The self-reported National Health and Nutrition Examination Survey (NHANES) prevalence estimates for MI ( Fig. 1.1 ) and angina pectoris ( Fig. 1.2 ) increase with age for both women and men. Data from NHANES that rely on self-reported MI and angina from health interviews probably underestimate the actual prevalence of advanced CAD. Advanced occlusive CAD often exists with few symptoms or overt clinical manifestations.

Across the United States heart diseases head the list of direct health expenditures, costing approximately $100 billion per year. Approximately 60% of costs are attributable to hospitals, 16% to medications, 11% to physicians, 7% to nursing homes, 5% to home health care, and the remaining small percentage to other costs. Lost productivity due to heart diseases is estimated to cost society another $100 billion.

There are 7 million healthcare discharges per year in the United States that have included cardiovascular procedures, and only obstetrical procedures are more common. Approximately 7.5 million inpatient cardiovascular procedures are performed in the United States annually. Some of the inpatient cardiovascular procedures that are particularly relevant to ASCVD, listed in descending order from more common to less common along with the annual frequency, are cardiac catheterization (1,029,000 per year), percutaneous coronary intervention (500,000 per year), surgical cardiac revascularization (397,000 per year), and pacemaker implantation (370,000 per year).

A Global Burden of Disease Study Group report from 2013 estimated that 17.3 million deaths worldwide in 2013 were related to ASCVD, a 41% increase since 1990. Although the absolute numbers of ASCVD deaths had increased significantly since 1990, the age-standardized death rate decreased by 22% in the same period, primarily due to shifting age demographics and causes of death worldwide. In a 2009 report that used US NHANES data, MI prevalence was compared by sex in middle-aged individuals (35 to 54 years) during the 1988–1994 and 1999–2004 time periods. Although MI prevalence was significantly greater in men than women in both time periods (2.5% vs 0.7% in 1988–1994 and 2.2% vs 1.0% in 1999–2004), the results suggested trends toward a decrease in prevalence for men and an increase in women.

Autopsy data have documented a reduced prevalence of anatomic CAD over time in both the general population and military personnel. In an analysis of 3832 autopsies performed on US military personnel (98% male, mean age 26 years) who died of combat or unintentional injuries between October 2001 and August 2011, the prevalence of CAD was 8.5%. This represents a marked decline in the prevalence of autopsy-documented CAD compared with rates seen during the Korean War in the 1950s (77%) and the Vietnam War in the 1960s (45%).

Incidence

Historically, the incidence of ASCVD includes both morbid events (angina pectoris, MI) and death outcomes (cardiovascular disease death). Identification of morbid events can be challenging because assignment of an event requires review of hospital records and standardization of the adjudication process. This approach has been undertaken in cohort studies, registries, and occasionally in other groups such as adults followed in an insurance program. In addition, criteria for morbid events are in constant evolution. As an example, in the 1950s the diagnosis of an MI was largely based on electrocardiographic (ECG) information. Over time the diagnosis could be made on the basis of changes in blood tests such as troponin, as they have become increasingly more accurate, reliable, and capable of identifying smaller MIs than in the past. Similarly, diagnosis of angina pectoris has evolved to be based on a composite of history and evaluation of ischemia with a variety of diagnostic modalities such as exercise and pharmacologic testing coupled with ECG and imaging—techniques that have led to greater accuracy.

The following observations concerning lifetime incidence of CAD have been noted.

In Americans over 55 years of age, those with an optimal risk-factor profile (total cholesterol level < 180 mg/dL, blood pressure (BP) < 120/80 mm Hg, nonsmokers, no diabetes) had substantially lower risks of ASCVD death through the age of 80 years than participants with two or more major risk factors (4.7% vs 29.6% in men, 6.4% vs 20.5% in women). Those with an optimal risk-factor profile also had lower lifetime risks of fatal CHD or nonfatal MI (3.6% vs 37.5% among men, < 1% vs 18.3% among women) and fatal or nonfatal stroke (2.3% vs 8.3% among men, 5.3% vs 10.7% among women). Similar trends within risk-factor strata were observed among blacks and whites and across diverse birth cohorts ( Table 1.1 ). Berry et al. concluded that an individual’s risk-factor burden translated into marked differences in the lifetime risk of cardiovascular disease, and these differences are consistent across race and birth cohorts. For total coronary events, the incidence rises steeply with age, with women lagging behind men by 10 years.

Despite a lack of symptoms, the extent of nonobstructive CAD is associated with a worse prognosis compared to adults without CAD. In a retrospective cohort study of American veterans without prior CAD who underwent coronary angiography and were followed for 1 year, the risk of MI over the ensuing year increased significantly and progressively in proportion to the extent of both nonobstructive (at least 1 stenosis ≥ 20% but < 70%) and obstructive (at least 1 stenosis ≥ 70%) CAD.

Concerning the incidence of MI, the Atherosclerosis Risk in Communities (ARIC) Study in the United States has been a key source of information for the past 30 years, and recent results are shown in Fig. 1.3 . Black men have the greatest incidence, followed by white men, black women, and white women. In general, women lag behind men in incidence by 20 years, but the sex ratio for incidence narrows with advancing age. The incidence at ages 65 to 94 versus ages 35 to 64 more than doubles in men and triples in women. In premenopausal women, serious manifestations of coronary disease, such as MI and SCD, are relatively rare. Marked disparities in ASCVD health and treatment persist between the sexes, and more women die from ASCVD than men. Despite a recent overall decline in ASCVD death rates, the burden of ASCVD death rates for women younger than 55 years has not changed over the last 2 decades. ASCVD risk factors are more prevalent among women, as is mortality from acute MI. It is unclear if these disparities persist due to pathophysiologic factors that affect ASCVD risk uniquely in women, or if they are related to differences in how detection and treatment algorithms are administered in women versus men.

The incidence of CAD, especially CAD mortality, has decreased since the 1970s in developed countries. Information on trends for total CAD that includes angina pectoris, MI, and coronary death is difficult to acquire. Only long-term cohort studies have such data, and the investigations have largely been concentrated in the United States. An analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and Kaiser Permanente Southern California (KPSC) enrollees with baseline lipid measurements in 2003 to 2007 compared the recent experience to that for the ARIC study participants with baseline measurements in 1987 to 1989. The authors showed that CHD rates have declined in recent years and the association between lipids and CHD in contemporary studies may be attenuated by the preferential use of statins by high-risk individuals.

Despite the declining incidence of CAD mortality in the United States, reductions in the incidence of MI have not been as large as might be expected. In addition, the use of the more sensitive troponin assays, which began around 2000 and leads to the diagnosis of MI when less of the myocardium is infarcted, could potentially mask a reduction in MI incidence over time.

There has been a relative increase in non-ST elevation MI (NSTEMI) in relation to ST elevation MI (STEMI) in recent years. For example, a report from the National Registry of Myocardial Infarction reviewed over 2.5 million MIs between 1990 and 2006 and found that the proportion of MIs due to NSTEMI increased from 19% in 1994 to 59% in 2006. This change in proportion was associated with an absolute decrease in the incidence of STEMI and either a rise (using MI defined by either CK-MB or troponin criteria) or no change (using MI defined by only CK-MB criteria) in the rate of NSTEMI.

In summary, the incidence of ischemic CHD has declined in the United States over the past 40 years. Modern lab testing can identify smaller MIs than in the past, and the role of cholesterol levels has become more complex because of greater use of lipid-lowering medications.

Coronary Artery Disease Mortality

Heart disease mortality has declined since the 1970s in the United States and in regions where economies and healthcare systems are relatively advanced. Ischemic heart disease remains the number one cause of death in adults on a worldwide basis. In a 2014 study using World Health Organization data from 49 countries in Europe and northern Asia, over 4 million annual deaths were attributable to ASCVD. Current worldwide estimates for heart disease mortality show Eastern European countries have the highest ASCVD death rates (> 200 per 100,000/year), followed by an intermediate group that includes most countries with modern economies (100–200 per 100,000/year), and the lowest levels (0–100 per 100,000/year) are largely observed in European countries and a few non-European countries with advanced healthcare systems ( Table 1.2 ). A detailed analysis of European country-specific data showed that CHD mortality rates dropped by more than 50% over the 1980–2009 interval, and the decline was observed across virtually all European countries for both sexes. The authors of the report concluded that the downward trends did not appear to show a plateau. Rather, CHD mortality was stable or continuing to decline across Europe. Complementary analyses have been undertaken in the United States, and CHD mortality has been demonstrated to have peaked in the 1970s and declined since that date.

The 2016 Heart Disease and Stroke Statistics update of the AHA shows that the 2013 overall death rate from ASCVD was 230 per 100,000/year and the CHD death rate is approximately 100 per 100,000/year ( Fig. 1.4 ). The death rate is higher in men than in women (3 times higher at ages 25 to 34, falling to 1.6 times at ages 75 to 84) and in blacks than in whites, an excess that disappears by age 75. Among the Hispanic population, coronary mortality is not as high as it is among blacks and whites.

The trends in mortality rates for ASCVD and CAD in men and women and in blacks and whites have fallen in most developed countries by 24% to 50% since 1975, although the decline has slowed since 1990. From 1996 to 2006 the ASCVD death rate declined by approximately 29%. This trend has been associated with reductions in both total CAD and in the CAD case fatality rate. The causes of the reduction in CAD mortality have been evaluated in adults between the ages of 25 and 84 in the United States from 1980 to 2000. Approximately half of the decline was due to improvements in therapy, including secondary preventive measures after MI or revascularization, initial treatments for acute coronary syndromes, therapy for heart failure, and revascularization for chronic angina. The other half of this effect was due to changes in risk factors, including reductions in total cholesterol (24%), systolic BP (20%), smoking prevalence (12%), and physical inactivity (5%). These changes were partly offset by increases in body mass index (BMI) and the prevalence of diabetes, which together accounted for an 18% increase in the number of deaths.

The international trends in CAD mortality are similar in many regions. Improvement in outcomes has been common in developed countries. Results have been variable in Eastern Europe, and some countries have shown an increase in CAD mortality in the early 1990s followed by a subsequent decline (Poland and the Czechia). The highest CAD mortality has been noted in the Russian Federation (330 and 154 per 100,000 in men and women, respectively, from 1995 to 1998). These values were similar to those in the period from 1985 to 1989. In Japan, CAD mortality has historically been much lower than in the United States and Europe. Mortality from CAD is expected to increase in developing countries (including China, India, sub-Saharan Africa, Latin America, and the Middle East), from an estimated 9 million in 1990 to a projected 19 million by 2020. This projected increase is thought to be a consequence of social and economic changes in non-Western countries, leading to decreased life expectancy, Westernized diets, physical inactivity, and increases in cigarette smoking.

Silent Myocardial Ischemia and Infarction

Although many MIs appear to occur without warning, there is a large reservoir of detectable advanced silent CAD from which these apparently sudden events evolve. Such individuals may have asymptomatic ischemic disease. The most specific ECG indication of silent myocardial ischemia is the development of a Q-wave MI in the absence of typical symptoms. Diabetes mellitus is an established risk factor for unrecognized MI, and the Multiethnic Study of Atherosclerosis (MESA) investigators have described a higher prevalence of unrecognized MI in participants with impaired fasting glucose. Researchers from Rotterdam have shown that the long-term prognosis for cardiovascular mortality and noncardiovascular mortality in men and women with unrecognized MI is worse than in those without MI. Although the incidence of both unrecognized and recognized infarctions increases with the severity of hypertension, the fraction that goes undetected is substantially greater in hypertensive than in normotensive persons. This predisposition to hypertension persisted even when patients with diabetes, antihypertensive therapy, and left ventricular hypertrophy (LVH) were excluded.

Sudden Cardiac Death

Survival after cardiac arrest is highly related to the type of treatment that is received immediately. The Resuscitation Outcomes Consortium has reported on the success of emergency therapy since 2006. Approximately 45% survival has been shown for bystander cardiopulmonary resuscitation, and in descending order lower survival rates have been observed for the following categories: first rhythm shockable, emergency medical services at the scene, and layperson use of automated external defibrillator.

There is a clear relationship between SCD and CAD. Clinical and autopsy studies and data from death certificates have found that 62% to 85% of patients who experience out-of-hospital SCD have evidence of prior CAD, 10% have other structural cardiac abnormalities, and 5% have no structural cardiac abnormality. A surveillance study of SCD from Ireland concluded that successful resuscitation of SCD was especially associated with ventricular fibrillation as the presenting rhythm.

SCD is the initial clinical coronary event in 15% of patients with CAD. Most sudden deaths are cardiac. Arrhythmias and ischemic heart disease are the most common antecedents. Severe left ventricular systolic dysfunction is a key risk factor for sudden death in patients with ischemic or nonischemic cardiomyopathy. In the Oregon Sudden Unexpected Death Study(Ore-SUDS), women were significantly less likely than men to have severe left ventricular dysfunction (odds ratio [OR] 0.51) or diagnosis of CAD (OR 0.34).

Exertion may precipitate SCD during the time of the increased physical activity or after the activity has stopped. As an example, a recent Finnish study showed increased SCD risk with skiing, cycling, and snow shoveling. The authors concluded that SCD during or immediately after exercise was related to male gender, ischemic heart disease, cardiac hypertrophy, and myocardial scarring. For more information on this topic see Chapter 22 on SCD.

Traditional Risk Factors

Many risk factors have been proposed for CAD. Greater age is an especially important determinant, and men experience greater risk for CAD than women throughout most of adulthood. In the worldwide INTERHEART study of patients from 52 countries, the authors identified nine potentially modifiable factors that accounted for over 90% of the population-attributable risk of a first MI: smoking, dyslipidemia, hypertension, diabetes, abdominal obesity, psychosocial factors, daily consumption of fruits and vegetables, regular alcohol consumption, and regular physical activity. More information for each of these topics is provided in the following discussion.

Smoking

Current cigarette smoking typically doubles the risk of CAD events. Relative risks may be much higher for heavy smokers. Older research has shown that filter and nonfilter cigarettes have similarly adverse effects on CAD risk. Quitting smoking in persons with CAD is associated with improved long-term survival, and the benefit of smoking cessation is evident within a few years of stopping, as shown in the Multiple Risk Factor Intervention Trial. The prevalence of current smoking in the United States has declined over the last 50 years and is now in the 15% to 25% range for men and 5% to 25% range for women ( Fig. 1.5 ).