Michael Jolly and Leslie Cho
GLOBAL BURDEN
It is widely acknowledged that cardiovascular diseases (CVDs) became the leading cause of mortality and a major cause of morbidity in adults worldwide over the course of the 20th century. Of these diseases, coronary artery or coronary heart disease (CAD) is the single most common cause, accounting for well over 42% of all CVD-related death.1 The World Health Organization (WHO) global burden of disease (GBD) project estimates that >7 million deaths were attributable to CAD in 2004. More than 5.8 million new cases of CAD are added yearly. In order to further define the societal effects, the GBD designed a new measure to capture the effect of years of life lost as a result of both premature death and disability. This metric is termed the disability-adjusted life-year or DALY and reflects a year of healthy life lost to disease. In 2004, CAD accounted for the loss of nearly 62 million DALYs worldwide, making it the fourth leading cause overall, behind lower respiratory infections, diarrheal diseases, and depression (Table 38.1).1
TABLE
38.1 Worldwide Burden of CAD and CVD, 2004
CAD, coronary artery disease; CVD, cardiovascular disease; AFR, Africa; AMR, America; EUR, Europe; SEAR, South East Asia region; WPR, Western Pacific region; EMR, Eastern Mediterranean region; DALY, disability-adjusted life years. Data obtained from the World Health Organization.
Global Temporal Trends in Coronary Artery Disease
Great strides were made in the latter half of the 20th century in the identification and management of traditional risk factors and in the therapeutics and management of acute coronary events, to combat the rising tide of coronary disease. These efforts resulted in dramatic reductions in coronary event rates and CAD-related mortality, mostly in developed countries such as those of Northern Europe. Between the mid-1980s and the mid-1990s, coronary event rates decreased roughly 23% in women and 25% in men, while CAD-related mortality decreased 34% in women and 42% in men. One-third of this reduction in CAD disease burden is attributable to improved therapeutics, whereas two-thirds is attributed to better identification and management of risk factors, leading to a decrease in acute coronary event rates.
Despite these improvements, the trend has been reversed, and we are currently in the midst of a dramatic resurgence in CAD morbidity and mortality. Between 1990 and 2020, worldwide CAD mortality is expected to increase 100% in men and 80% in women. The majority of that increase is expected to occur in the developing world, where rates of CAD mortality are expected to increase 137% in men and 120% in women, whereas in developed countries, the increases are a bit more modest, 48% in men and 29% in women. In terms of DALYs lost, the expected rise is nearly 40%, from 59 to 82 million. The basis for this astounding increase in CAD in the developing world is explained largely by the tightly linked relationship between disease prevalence and various socioeconomic factors. Reductions in mortality from infectious diseases and malnutrition paired with economic prosperity have led to longer life spans worldwide. Along with these changes, modernization and industrialization have led to a decrease in physical activity, increased availability, and consumption of a high-fat, high-calorie diet. These observations, often termed “epidemiological transitions,” occur when a shift occurs in the predominant cause of morbidity and mortality for a given region.2 In the developing world, all of these factors have contributed to rising rates of obesity, diabetes, and lipid disorders that are now well established in the developed, western world.
BURDEN IN THE UNITED STATES
Although the mortality rates from CAD have declined since 1968, it remains the most common manifestation of atherosclerotic CVD and the single most common cause of adult death in the United States, accounting for one of every five, and, in people over the age of 35 years, one of every three (Figs. 38.1 and 38.2; Table 38.2). CVD has accounted for more deaths in the United States than any other major cause every year since 1900 except 1918.3 According to the American Heart Association, 406,351 people died from CAD in 2007, many at the peak of their productive lives. Currently, >16 million people are afflicted with CAD in the United States, with 1.3 million new cases of myocardial infarction (MI), or one every 25 seconds! Of this number, 785,000 represent new cases, whereas 470,000 are recurrent. By comparison, approximately 865,000 people per year suffered a MI from 1987 to 2000, 565,000 per year being new cases. Importantly, 21% of all new MIs in 2007 were symptomatically silent. In terms of societal impact, CAD accounted for the loss of roughly 6.5 million DALYs in 2004, while the estimated average number of years of life lost due to MI is 16.6. It is the leading cause of premature permanent disability, accounting for 19% of Social Security disability outlays.3
FIGURE 38.1 Proportion of CVD as CAD by age and sex, from Framingham Study, 26-year follow-up. (Reprinted from Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J. 1986;111(2):383–390, with permission from Elsevier.)
FIGURE 38.2 Prevalence of coronary heart disease by age and sex (National Health and Nutrition Examination Survey: 2005–2008. National Center for Health Statistics and National Heart, Lung, and Blood Institute. *Myocardial infarction diagnosis by expert committee based on review of hospital records.) (From Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209, with permission.)
TABLE
38.2 Burden of CAD in the United States, 2008
Data are for people age 20 years and older.
aData are for people of all ages.
Roger VL, Go AS, Lloyd-Jones DM, et al.; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209, with permission.
Unrecognized and Silent Myocardial Ischemia and Infarction
The estimated prevalence of asymptomatic significant CAD that is detectable by stress testing or ambulatory ECG is 2% to 4% in the United States.4 Silent ischemia is actually the most common manifestation of clinically significant CAD, even more so than angina. The prevalence of silent myocardial ischemia in men with two or more traditional coronary risk factors (smoking, hyperlipidemia, family history, diabetes, age, hypertension, age >45 years, and obesity) is upwards of 10%. Of these patients, more than half will go on to develop overt clinical manifestations of CAD and come to medical attention. Further, often (75% in one study) these patients have multivessel disease when further investigated. In patients with known coronary disease and stable angina, the prevalence of silent ischemia is estimated to be between 25% and 50%. Additionally, 70% to 80% of ischemic episodes in patients with stable angina are silent. Unrecognized MI has two components, asymptomatic or silent MI (approximately 50%), and that which is associated with such atypical symptoms that infarction is not entertained as part of the differential (approximately 50%). One in three MIs can actually be classified as unrecognized. The long-term morbidity and mortality of silent ischemia and unrecognized MI is similar to that of recognized MI (Figs. 38.3 and 38.4).5
FIGURE 38.3 Outcome of patients with angina (Group 2) or silent ischemia (Group 2) and exercise-induced ST depression in the Coronary Artery Surgery Study (CASS) registry. Controls had no objective evidence of ischemia. (Reprinted from Weiner DA, Ryan TJ, McCabe CH, Ng G. Risk of developing an acute myocardial infarction or sudden cardiac death in patients with exercise induced silent myocardial ischemia: a report from the Coronary Artery Study (CASS) Registry. Am J Cardiol. 1988;62(17):1155–1158, with permission from Elsevier.)
FIGURE 38.4 Long-term outcome of patients post myocardial infarction with angina versus silent ischemia versus no objective ischemia. SMI, silent myocardial ischemia; CABG, coronary artery bypass grafting; PTCA, percutaneous coronary angioplasty; MI, myocardial infarction. (With kind permission from Springer Science+Business Media: Essential Atlas of Heart Diseases, 2005, Braunwald E.)
Diabetic and hypertensive patients seem to be most susceptible to unrecognized MI.
Age and Gender Variation
The average age of a person presenting with a first MI in the United States is 65 years for men and 70 years for women. Figures 38.2 and 38.5 provide a sense of how strongly the prevalence and incidence of CAD is influenced by age and gender. The incidence of serious manifestations of CAD, such as MI or death, more than doubles between the age ranges of 65–74 and >85 for men and nearly quadruples for women. Further, data from the Centers for Disease Control (CDC) demonstrate that 83% of people who die from CAD are 65 years or older. After age 40 years, men have a lifetime risk of developing CAD of 49%, while women have a risk of 32%. After 70 years this risk decreases to 35% for men and 24% for women.6
FIGURE 38.5 Incidence of myocardial infarction* by age, race, and sex (Atherosclerosis Risk in Communities Surveillance, 1987–2004). *Myocardial infarction diagnosis by expert committee based on review of hospital records. (From Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209, with permission.)
The incidence of any manifestation of CAD in women lags behind that in men by 10 years, whereas the incidence of MI or sudden death lags by 20 years. In fact, excluding people >75 years of age, women are much more likely to present with angina as their first manifestation of CAD, whereas men more often present with MI (Fig. 38.6). In terms of CAD mortality, gender differences narrow significantly with age. Between the ages of 45 and 64 the 1-year mortality following a first MI is 5% for white men, 14% for black men, 9% for white women, and 8% for black women. However, after the age of 65, 30% of women (white or black) will die within 1 year compared to only 25% of men (white or black).3
FIGURE 38.6 First manifestation of CAD in men and women by age. MI, myocardial infarction. (Reprinted from Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J.1986;111(2):383–390, with permission from Elsevier.)
Finally, menopause, whether natural or surgical, has a significant influence on the incidence and severity of CAD. Indeed, the incidence of serious manifestations of CAD is rare in premenopausal women but increases more than threefold in age-matched postmenopausal women. Of note, polycystic ovarian disease increases the likelihood of premature CAD in women.3
Racial and Socioeconomic Disparities
CAD is the leading cause of death in the United States for every major ethnic group. The self-reported prevalence of CAD and MI and the CAD mortality rates in various racial and ethnic groups according to the latest AHA update are shown in Table 38.2 and Figure 38.7. The most conspicuous feature of these data is that the CAD mortality rate is highest among blacks overall. Indeed, the mortality rate among black Americans is 1.6 times that of whites, a ratio that has not changed since the 1950s.7 This difference is particularly striking among younger people, aged 35 to 44 years, in whom the mortality among blacks is reported to be 50% higher than among whites. This difference disappears by age 75 years. Additionally, the incidence of CAD is particularly high among South Asians. The mortality rate among East Asians, Hispanics, and Native Americans or Alaskans is not nearly as high as that among whites or blacks. In terms of socioeconomic differences, numerous studies have linked lower income levels, lower educational levels, and other social factors to elevated CAD risk. One recent study showed a 2.5- to 3-fold increased risk in people living in poorer neighborhoods compared with those living in higherincome neighborhoods, even after adjusting for other socioeconomic and traditional risk factors.8
FIGURE 38.7 Age-adjusted death rates for coronary heart disease by race/ethnicity and sex, U.S., 2006. (Morbidity & Mortality: 2009 Chart Book on Cardiovascular, Lung, and Blood Diseases. 2009, National Institutes of Health.)
CAD in the Young
Symptomatic CAD in people under the age of 40 to 45 years is a fairly uncommon problem. In autopsy studies, however, the prevalence of anatomic CAD is roughly 20% in men and 8% in women aged 30 to 34 years.3 This is consistent with the finding of a delay in manifestations of CAD in women versus men and that atherosclerosis, despite its relative rarity in the young, is a process that begins at an early age. People presenting with CAD at a young age tend to have multiple risk factors as well as a significant family history of premature CAD. Tobacco use is very common among this population; however, the prevalence of dyslipidemia is similar to those presenting later in life. Often, this population tends to have some manifestations of the metabolic syndrome, such as low HDL, elevated triglycerides, and glucose intolerance. With the current epidemics of obesity and the metabolic syndrome in the United States, it seems likely that the incidence of symptomatic CAD in young people is either on the rise currently, or soon will be.
Temporal Trends in CAD
Autopsy studies over the past few decades have shown a decreasing prevalence of anatomically significant CAD in people 59 years of age and younger in the United States. From the periods 1979 to 1983 and 1990 to 1994, the prevalence of CAD decreased from 42% to 32% among men and from 29% to 16% among women.9 There was no change in those >60 years of age. Similarly, the incidence of clinically manifested CAD decreased from the 1970s to the 1980s. The National Health and Nutrition Examination Survey (NHANES) tracked two cohorts of patients from 1971 to 1982 and from 1982 to 1992 and found that the prevalence of CAD over these time periods decreased from 133 to 114 cases per 10,000 persons per year of followup. Over a similar time period, the overall incidence of MI remained relatively stable. However, from 2000 to 2008 the incidence of MI decreased from 287 cases per 100,000 person-years to 208 cases per 100,000 person-years, a relative decrease of 24%. This was even more impressive among patients with ST-segment elevation MI (STEMI) where from 1999 to 2008 there was a relative decrease of 62%, from 133 to only 50 cases per 100,000 persons. For non–ST-segment elevation MI (NSTEMI), the incidence actually increased between 1999 and 2004, from 155 to 202 cases per 100,000 persons, likely reflecting the newer and more sensitive troponin assays being widely utilized. Even still, the incidence of NSTEMI has been decreasing since 2004 (Fig. 38.8).10
FIGURE 38.8 Age- and sex-adjusted incidence rates of acute myocardial infarction, 1999 to 2008. Bars represent 95% confidence intervals. MI denotes myocardial infarction, and STEMI ST-segment myocardial infarction. (From Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010;362(23):2155–2165, with permission from the Massachusetts Medical Society.)
In the United States, coronary heart disease mortality has declined steadily since it reached a peak in the mid-1960s (Fig. 38.9). The WHO estimated that between 1965 to 1969 and 1995 to 1997, overall CAD death rates declined 63% in men and 60% in women. Data from the Framingham study echo this, demonstrating a 59% reduction in CAD mortality and a 49% reduction in the rate of sudden cardiac death (SCD) from 1950 to 1999.3 Additionally, from 1990 to 1999, in-hospital mortality rates for acute MI declined from 11.2% to 9.4%. However, this trend is showing signs of slowing; the CDC found only a 27% reduction from 1992 to 2002. This is likely attributable to the epidemics of obesity, diabetes, and the metabolic syndrome in the United States at the end of the twentieth century.3
FIGURE 38.9 Age-adjusted death rates for coronary heart disease, U.S., 1980 to 2006. (Morbidity & Mortality: 2009 Chart Book on Cardiovascular, Lung, and Blood Diseases. 2009, National Institutes of Health.)
Prognosis and Risk of Sudden Cardiac Death
Once an individual has been diagnosed with stable angina, prognosis shifts to a much higher risk stratum. The risk of future events, in particular subsequent MI, is increased, whereas survival is dramatically reduced with increasing age. The effect of age at presentation on risk of future events is more profound for women than for men. Overall, however, men remain at higher risk of subsequent MI and death at all age strata (Figs. 38.10 and 38.11).11
FIGURE 38.10 Risk of subsequent MI or cardiac death after being diagnosed with angina, stratified by sex. (Adapted from Orencia A, Baily K, Yaun P, et al. Effect of gender on long-term outcome of angina pectoris and myocardial infarction/sudden unexpected death. JAMA1993;269:2392–2397)
FIGURE 38.11 Long-term survival after the diagnosis of uncomplicated angina, stratified by age and sex. (Adapted from Orencia A, Bailey K, Yawn BP, et al. Effect of gender on long-term outcome of angina pectoris and myocardial infarction/sudden unexpected death. JAMA.1993;269(18):2392.)
Survivors of acute MI have 1.5 to 15 times the morbidity and mortality rate as the general population, depending on age, gender, and clinical outcome of the inciting event. In contrast to stable angina, the incidence of future adverse cardiovascular events in people after their initial recognized MI is, in general, higher in women than in men (Fig. 38.12). Following a recognized acute MI, the 1-year mortality rate in men is 25%, whereas in women it is significantly higher, 38%. The majority of this risk occurs within the first 30 days after the event.3 The discrepancy between the male and female mortality and event rates can be explained by the later age and greater burden of risk factors on average at initial presentation in women.
FIGURE 38.12 Prognosis after myocardial infarction, from Framingham Study, 36-year follow-up. MI, myocardial infarction; SCD, sudden cardiac death; CHF, congestive heart failure. (From Kannel WB. Prevalence, incidence, and mortality of coronary heart disease. In: Atherosclerosis and Coronary Artery Disease. Lippincott Williams & Wilkins, 1996.)
Sudden cardiac death (SCD), mostly due to out-of-hospital ventricular fibrillation, accounts for >50% of total CAD-related mortality. In the United States, there are approximately 300,000 out-of-hospital emergency medical services (EMS)-assessed cardiac arrests. Only one-third of patients treated by EMS for cardiac arrest have symptoms within 1 hour of death. The mean survival rate following ventricular fibrillation is 21%, whereas the median survival rate to hospital discharge with any first-recorded rhythm is 7.9%.12 The risk of SCD death in a person after the index MI is four to six times higher than for the age-matched general population. This risk also varies significantly as a function of age, gender, and race. Overall, from 70% to 89% of all SCD cases occur in men, and the incidence of SCD is three to four times greater in men than in women. This disparity decreases as women age and their risk increases. Blacks have an estimated twofold higher incidence of 30-day mortality following discharge after SCD, a disparity likely related to health care access and a higher incidence of congestive heart failure.3
Cost and Health Care Resource Utilization
Direct and indirect costs related to coronary heart disease exceeded $177 billion in the United States in 2007. This represents nearly half of the total cost related to all CVDs, including stroke, hypertension, and congestive heart failure, which reached a staggering $287 billion for the same year (Table 38.3). In contrast, 2007 costs related to all forms of cancer were estimated to be $219 billion. Medicare estimates that the cost of CAD-related hospitalizations exceeded $14,000 for acute MI, $12,900 for coronary atherosclerosis, and $10,600 for “other” CAD diagnoses, per discharge, in 2006.3
TABLE
38.3 2007 Estimated Direct and Indirect Costs (in Billions of Dollars) of EfiBI CVDs In the United States
aIncludes coronary heart disease, congestive heart failure, part of hypertensive disease, cardiac dysrhythmias, rheumatic heart disease, cardiomyopathy, pulmonary heart disease, and other or ill-defined heart diseases.
bCosts due to hypertensive disease are limited to hypertension without heart disease
cEarnings of persons who died in 2007, discounted at 3%.
From Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209, with permission.
Despite rising overall costs, the actual number of patients hospitalized fell 42% between 1997 and 2007, from 2.1 million to 1.6 million. In 2007, it was estimated that 1.1 million diagnostic cardiac catheterizations, 1.2 million percutaneous coronary interventions, and 408,000 bypass operations were performed in the United States.
RISK FACTORS
Traditional Modifiable Risk Factors
Epidemiologic studies undertaken in the latter half of the twentieth century have firmly established links between certain demographic and clinical factors as well as social habits and the diagnosis of coronary heart disease. Among these, older age, dyslipidemia, hypertension, tobacco smoking, male sex, diabetes mellitus, and family history of premature coronary disease are among the more common and well recognized. Risk scores, most commonly the Framingham Risk Score, have been developed using these and other risks to predict accurately the long-term risk of CAD events. More than 90% of people carrying the diagnosis of CAD have one of the following major risk factors: hypertension, hyperlipidemia, treatment for hypertension or hyperlipidemia, or diabetes. Further the INTERHEART study of >29,000 patients in 52 countries showed that >90% of the risk of an index MI is attributable to the following factors regardless of gender, ethnicity, or geography: tobacco, hyperlipidemia, hypertension, diabetes, obesity, sedentary lifestyle, alcoholism, low intake of fruits and vegetables, and psychosocial index.3
Tobacco
According to the AHA, in 2009 >46 million Americans 18 years of age and older are active cigarette smokers, representing nearly 21% of the total population. This constitutes 23% of all men and 18% of all women in the United States. While the total number has decreased by 3.5% since 1998, the number of new smokers every year has seemingly plateaued at approximately 2.4 million. Even more discouraging, most new smokers (58.8%) in 2008 were <18 years of age. From 1980 to 2002 the number of high school seniors who had smoked within the past month declined 12.5%, and since 1965, smoking among persons 18 years of age and older has decreased 47% overall. The prevalence of smoking is highest among white men (25%), black men (23%), white women (21%), and black women (19%). Of all ethnic groups, Asians and Hispanics had the lowest overall prevalence. Smokers have a two- to fourfold higher risk of CAD than nonsmokers, and two- to threefold higher risk of CAD-related mortality, and twofold greater risk for stroke. Even more striking, smokers have a >10-fold risk of developing peripheral artery disease than nonsmokers.13 The INTERHEART study estimated that tobacco accounts for 36% of the population attributable risk of a first MI.3 Importantly, it is estimated that the total estimated cost of smoking to society, including direct medical costs and lost productivity, was $193 billion per year between 2000 and 2004.
Smoking cessation has proven benefits for CAD. According to the WHO, the risk of CAD decreases by 50% 1 year after abstention, and within 15 years the relative risk of death from CAD for an ex-smoker becomes equivalent to that of a lifetime nonsmoker.
Lipids
The prevalence of lipid disorders in patients with CAD and in the general population is extraordinarily common. Of people with premature CAD, 75% to 85% have dyslipidemia. In the United States in 2008, approximately one-third of all adults >20 years of age had an LDL cholesterol ≥130 mg/dL. For further details on dyslipidemia and its effects on coronary disease, refer to Chapter 15.
Hypertension
According to AHA figures, 76 million Americans carried the diagnosis of hypertension in 2008. An additional 59 million people are classified as having prehypertension (systolic blood pressure 120 to 139 mm Hg, or diastolic blood pressure 80 to 89 mm Hg) and are at risk for overt hypertension. Systolic blood pressure, diastolic blood pressure, and pulse pressure have all been separately identified as risk factors. The prevalence of hypertension in blacks in the United States is among the highest in the world and continues to increase.6 From 1988 to 2002, the prevalence increased from 35.8% to 41.4%.13According to the INTERHEART study, hypertension accounts for 18% of the population attributable risk of first MI.3 Further details on hypertension and its cardiovascular effects are included in Chapter 52.
Diabetes Mellitus
The prevalence of physician-diagnosed and undiagnosed diabetes mellitus among adults in the United States was 25.4 million in 2008. An additional 81.5 million (37%) have prediabetes, with fasting blood glucose of 100 to <126 mg/dL. From 1990 to 2002, the prevalence of diabetes increased 61% in the United States. Mexican Americans and blacks currently have the highest rates of any ethnic group.13 The prevalence of diabetes in individuals 40 to 74 years of age is 11.2% for whites, 18.2% for blacks, and 20.3% for Hispanics. Despite the higher prevalence in Hispanics, blacks were more likely to die from diabetes.7 Worldwide, the prevalence among all ages is 2.8%, and it is expected to nearly double to 4.4% by 2030. Diabetes increases the risk of MI or cerebrovascular accident by two- to threefold and doubles the risk of SCD. According to the INTERHEART study, diabetes accounts for 10% of the population attributable risk of first MI.3 In 2002 the National Cholesterol Education Program (NCEP) was compelled by these and additional statistics to elevate diabetes to the category of CAD equivalent.
Obesity and the Metabolic Syndrome
According to the AHA, over 149 million Americans (67%) were overweight or obese in 2008, with 75 million (34%) being overtly obese. Further, the prevalence of overweight and obese children has quadrupled since the 1960s, reaching 32% of all American children in 2008. Obesity has reached true epidemic proportions in the United States and shows no signs of slowing down in the near future. From 1999 to 2000 and from 2007 to 2008, the prevalence of obesity increased from 28% to 32% in adult men and 33% to 36% adult women, respectively.13 Mexican Americans constitute the ethnic group with the greatest prevalence. Obesity is now recognized as an independent risk factor for CAD, although it also mediates its effects through other factors that are highly associated with it, such as hypertension, insulin resistance, and hypertriglyceridemia. Obesity accounts for roughly 20% of the population attributable risk of a first MI.
The metabolic syndrome is defined by having ≥3 of the following: a fasting plasma glucose ≥100 mg/dL or undergoing drug treatment for elevated glucose, HDL cholesterol <40 mg/dL in men or <50 mg/dL in women or undergoing drug treatment for reduced high-density lipoprotein (HDL) cholesterol, triglycerides ≥150 mg/dL or undergoing drug treatment for elevated triglycerides, waist circumference ≥102 cm in men or ≥88 cm in women in the United States, or a BP ≥130 mm Hg systolic or ≥85 mm Hg diastolic or undergoing drug treatment for hypertension or antihypertensive drug treatment in a patient with a history of hypertension.14 The age-adjusted prevalence of the metabolic syndrome in U.S. adults is 34%.3 Among ethnic groups in the United States, Mexican Americans have the greatest prevalence. A diagnosis of metabolic syndrome carries with it an increased risk of overt diabetes mellitus, a twofold greater risk of CAD, an increased risk of CAD death.
Novel Risk Factors
In addition to the classic modifiable risk factors newer measures are emerging that are leading to new insights and confirming the role of inflammation in atherosclerosis. Not all of these factors have obvious treatments or are modifiable, and some may prove to be risk markers rather than truly play a pathophysiologic role. Among these, high-sensitivity C-reactive protein (hs-CRP) has been at the forefront, although not without controversy Levels of hs-CRP have been shown to predict the long-term risk of first MI and improve risk stratification along with serum lipids in a primary prevention setting. Even in patients who do not meet current pharmacologic treatment recommendations, the addition of statins to patients with elevated hs-CRP has been shown to decrease adverse cardiovascular events.3 Elevated serum homocysteine levels have similarly been shown to be linked with increased risk for CAD. Levels above the 95th percentile increase the risk of MI approximately threefold. Other novel markers that may prove useful in predicting cardiovascular risk include, fibrinogen, N-terminal fragment brain natriuretic peptide, small dense lipoproteins, apolipoproteins, lipoprotein-associated phospholipase A2, lipoprotein (a), cystatin C, uric acid, alanine aminotransferase, and gamma glutamyltransferase.15
Finally, peripheral vascular disease (PVD) as manifested by a cerebral vascular accident (CVA), transient ischemic attack, or lower-extremity claudication significantly increases the risk of CAD and coronary events. This is somewhat intuitive, given that many of the risk factors are shared. CVA increases the risk of CAD or cardiac failure twofold, whereas intermittent claudication increases the risk two- to threefold. Carotid intima-media thickness (IMT), a measure of carotid atherosclerotic disease as determined by ultrasound, has been shown to be predictive of future MI, even after controlling for traditional risk factors.16 This lends further support to the role of systemic inflammation in the pathobiology of atherosclerotic vascular disease.
SUMMARY
CVD remains the leading cause of death worldwide.
CVD remains the leading cause of death and health care expenditures in the United States, although the mortality rates have declined over the past several decades.
The incidence of CAD in women lags behind men by 10 years, whereas the incidence of MI in women lags behind men by 20 years.
In general, women are more likely to present with angina, whereas men tend to present with MI as their first manifestation of CAD.
African Americans have a CAD-related mortality rate that is 1.6 times higher than whites, a difference that is even more pronounced in younger populations.
The incidence of NSTEMI far out numbers the incidence of STEMI, although both have been declining in recent years.
SCD accounts for >50% of all CAD-related mortality
The prevalence of tobacco smoking has seemingly reached a plateau of approximately 20% and still accounts for 36% of the risk of first MI.
The prevalence of hypertension in African Americans is among the highest in the world and continues to increase.
Obesity, diabetes, hyperlipidemia, and the metabolic syndrome are all modifiable risk factors for coronary disease that are reaching near-epidemic proportions in the United States.
REFERENCES
1. Stevens G. Global health risks: progress and challenges. Bull World Health Org. 2009;87(9):646–646.
2. Gaziano TA, Gaziano JM. Global burden of cardiovascular disease. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia: Saunders/Elsevier; 2012:1–20.
3. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123(4):e18–e209.
4. Cohn PF, Fox KM, Daly C. Silent myocardial ischemia. Circulation. 2003;108(10):1263–77.
5. Weiner DA, Ryan TJ, McCabe CH, Ng G. Risk of developing an acute myocardial infarction or sudden cardiac death in patients with exercise induced silent myocardial ischemia: a report from the Coronary Artery Study (CASS) Registry. Am J Cardiol. 1988;62(17):1155–1158.
6. Anon. National Health and Nutrition Examination Survey NHANES 1999–2004. 2004.
7. Yancy CW Heart disease in varied populations. In: Bonow RO, Mann DL, Zipes DP, Libby P, editors. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia: Saunders/Elsevier; 2011:23.
8. Pleis JR, Ward BW, Lucas JW. Summary health statistics for U.S. adults: National Health Interview Survey, 2009. Vital Health Stat. 2010;(249):1–207.
9. National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI). Morbidity and Mortality: 2009 Chart Book on Cardiovascular, Lung and Blood Diseases. Bethesda, MD: NHLBI; 2009 Oct [cited 2012 Feb 27]. Available from: http://www. nhlbi.nih.gov/resources/docs/cht-book.htm
10. Yeh RW, Sidney S, Chandra M, et al. Population trends in the incidence and outcomes of acute myocardial infarction. N Engl J Med. 2010;362(23):2155–2165.
11. Orencia A, Bailey K, Yawn BP, Kottke TE. Effect of gender on long-term outcome of angina pectoris and myocardial infarction/sudden unexpected death. JAMA. 1993;269(18):2392–2397.
12. Nichol G, Thomas E, Callaway CW et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA. 2008;300(12):1423–1431.
13. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937–952.
14. Anon. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International. Circulation. 2009;120 (16):1640–1645.
15. Ridker PM, Danielson E, Fonseca F, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. NEJM. 2008;359(21):2195Y2207.
16. Dent THS. Predicting the risk of coronary heart disease. II: the role of novel molecular biomarkers and genetics in estimating risk, and the future of risk prediction. Atherosclerosis. 2010;213(2):352–362.
QUESTIONS AND ANSWERS
Questions
1. Which U.S. racial group has the highest mortality rate associated with coronary artery disease (CAD)?
a. Hispanics
b. Asians
c. Blacks
d. Whites
2. Which of the following regarding acute myocardial infarction (MI) in the United States is false?
a. The incidence of ST-segment elevation MI (STEMI) has declined over the past decade.
b. The in-hospital mortality has declined.
c. The incidence of non-ST-segment elevation MI (NSTEMI) increased with the advent of sensitive troponin assays.
d. Roughly 50% of all MIs are symptomatically silent.
3. Which of the following factors are associated with the epidemiologic transition of CAD becoming the leading cause of mortality in the United States during the 20th century?
a. Reduced incidence of infectious diseases and malnutrition
b. Increased life expectancy
c. Industrialization with shift in the type of workrelated activities
d. Increased availability of foods with high saturated fat content
e. All of the above
4. Which of the following patient is more likely to die within 1 year following their first MI?
a. A 55-year-old black man
b. A 70-year-old white woman
c. A 47-year-old white woman
d. A 60-year-old black woman
5. Which of the following related to cost is true?
a. The estimated total cost of all forms of cancer continues to exceed cardiovascular disease (CVD).
b. The majority of CAD-related costs come from hospital emergency room visits.
c. CAD-related costs are increasing due to increased patient hospitalizations.
d. Lost productivity accounts for the majority of CAD-related cost.
6. Which of the following statements related to smoking is false?
a. Smoking increases the risk of peripheral arterial disease by >10-fold.
b. The majority of new smokers start the habit during their early 20s, often while in college.
c. Cigarette smoking has a twofold greater risk of suffering a CVA.
d. The overall prevalence of smokers has decreased in the United States compared to the mid 20th century.
7. Which ethnic group has the highest prevalence of diabetes?
a. Whites
b. Hispanics
c. Asians
d. Blacks
8. Which of the following is not considered a criterion for the metabolic syndrome?
a. Having a fasting blood glucose ≥100 mg/dL
b. Undergoing treatment for hypertension
c. Having a body mass index (BMI) ≥ 30
d. Triglycerides ≥150 mg/dL
9. Treatment with statins has been shown to reduce the incidence of major cardiovascular events in nonhyperlipidemic patients with which abnormal novel risk marker?
a. High-sensitivity C-reactive protein (hs-CRP)
b. Alanine aminotransferase
c. NT-BNP
d. Cystatin C
10. All of the following are true regarding sudden cardiac death (SCD) except:
a. The incidence is higher in men than women.
b. The median survival rate following ventricular fibrillation is approximately 21%.
c. The risk of developing SCD is four to six times higher in patients following an index MI.
d. The most common presenting arrhythmia for SCD is polymorphic VT.
Answers
1. Answer C: Black Americans have a mortality that is 1.6 times that of white Americans. Additionally, blacks are more likely than whites to suffer from hypertension, diabetes, and obesity.
2. Answer D: It is estimated that roughly 21% off all new acute MIs were symptomatically silent in 2007. It is thought that silent MIs are associated with worse overall outcomes, largely due delayed diagnosis and risk factor progression. The incidence of STEMI has declined over the past several decades. Between 1999 and 2004, the incidence of NSTEMI actually increased, largely due to the widespread availability of sensitive troponin assays. Since 2004, they have gradually declined.
3. Answer E: All of the mentioned factors are contributory for CAD becoming the predominant cause of death in the United States for the past century. Many of the developing world countries are currently undergoing similar transitions with improvements in overall public health systems, cleaner water, more abundant food, and modernization and industrialization of industries. While the burden of infectious diseases and malnutrition decrease, the diseases associated with longer life such as cancer, hypertension, diabetes, and heart disease predominate.
4. Answer B: The incidence of any manifestation of CAD in women lags behind that in men by 10 years, whereas the incidence of MI or sudden death lags by 20 years. However, age is one of the strongest predictors of mortality in CAD, independent of race.
5. Answer D: Lost productivity from premature death accounts for an estimated $95 billion overall cost to society per year. This is in excess of the direct costs associated with hospitalizations, medications, outpatient visits, and emergency room visits combined. CVD expenditures exceed the cost of treating all forms of cancer. The most expensive direct expenditure for CVD comes from inpatient hospitalizations. The cost of CVD has increased despite a reduction in total yearly patient hospitalizations.
6. Answer B: The highest incidence of new smokers is observed in persons <18 years of age. According to a report from the Surgeon General, >80% of all smokers started smoking when <18 years, with the age of initiation most commonly being 14- and 15 years old. Cigarette smoking has declined in the United States when compared to the mid 20th century, however, since 2005 the prevalence seems to have plateaued at around 20%. Smoking is known to greatly increase the risk of PAD, stroke, and CAD.
7. Answer B: Hispanics have the highest prevalence of diabetes in the United States. However, mortality rates related to diabetes are highest among blacks.
8. Answer C: BMI is not part of the contemporary definition for the metabolic syndrome. However, a waist circumference ≥102 cm in men or ≥88 cm in women is included. All of the other factors are included. Of note, for each of the parameters involving glucose, hypertension, or lipids, the cutoff values are relevant only for people not already being actively treated. Once treatment has been initiated, that particular risk factor should be included in the required ≥3 for the definition.
9. Answer A: hs-CRP was shown in the large Jupiter study to be a potential modifiable risk marker when treated with rosuvastatin, even in patients without hyperlipidemia. Alanine aminotransferase, NT-BNP, and Cystatin C all have been loosely correlated with predicting adverse cardiovascular risk but not tested rigorously with regard to the effects statins have on them.
10. Answer D: The most common arrhythmia associated with SCD is VF, accounting for >50% of all CAD-related mortality. While survival following treated VF is as high as 21%, the median rate of survival to hospital discharge is <10%. Patients with documented CAD have far higher risk of developing SCD than the general population, as do patients with cardiomyopathies and other genetic predispositions.