Heart failure (HF) is a major public health issue that leads to substantial morbidity and mortality in the United States. Age, hypertension, and coronary ischemia are all well‐documented risk factors for HF in older adults, but less is known about the incidence, risk factors, and demographics associated with HF in younger people. The Coronary Artery Risk Development in Young Adults (CARDIA) study, a 20‐year multicenter longitudinal study of black and white men and women designed to investigate the development of coronary artery disease in young adults, offered an opportunity to explore these relationships.
Beginning in 1985–1986, persons 18 to 30 years of age were enrolled from 4 American cities: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California. The cohort was well balanced with respect to self‐reported race (52% black) and sex (55% women). Multiple clinical measurements, including blood pressure (BP), were obtained at baseline and after 2, 5, 7, 10, 15, and 20 years. BP was measured in standardized fashion, with hypertension defined as a BP of at least 140/90 mm Hg or use of antihypertensive medications. During both their study examinations and in yearly telephone follow‐up, participants were asked about overnight hospitalizations. For each hospitalization, records were obtained and adjudicated for the presence of incident HF, defined as a hospitalization where the final diagnosis of HF was made by a treating physician and HF was treated with at least a diuretic and either digitalis or an afterload‐reducing agent. Death was also reported to the study centers every 6 months, and each death was adjudicated to determine whether it was due to HF. In year 5, as part of the examination, participants underwent echocardiography. Systolic function was considered abnormal if the ejection fraction (EF) was either <40% or qualitatively described as abnormal; systolic function was considered borderline if the EF was 40% to 60%. Left ventricular hypertrophy (LVH) was defined as a left ventricular mass index at least 51 g/m. Using multiple statistical tools, the CARDIA investigators compared baseline and subsequent development of risk factors in participants in whom HF did and did not develop.
The CARDIA study enrolled 5115 individuals with a mean age of 25 years and a mean baseline BP around 110/70 mm Hg. The retention rate in the study was exceptionally high, with 87.5% of the original cohort completing the yearly telephone interview at year 20 and 71.8% completing the year 20 in‐person examination. During the 20 years of follow‐up, incident HF occurred in 27 patients (0.5%), which was more common than the incidence of myocardial infarction. Twenty‐six of the 27 patients who developed incident HF were black. The cumulative incidence of HF was 1.1% in black women and 0.9% in black men, compared with 0.08% in white women and 0% in white men. Death due to HF occurred in 3 black men (4.5% of all deaths in black men) and 2 black women (7.7% of all deaths in black women). There were no deaths due to HF in either white men or women.
As compared with black patients in whom HF did not develop, blacks with incident HF had higher mean baseline BP (120.6/78.7 mm Hg vs 111.4/68.7 mm Hg) and were also more likely to be obese (mean body mass index, 32.0 kg/m2 vs 25.2 kg/m2), diabetic (12% vs 2%), or have chronic kidney disease (8% vs 1%) at baseline. Not surprisingly, blacks with incident HF were also more likely to have borderline or abnormal systolic dysfunction or LVH when measured at year 5. Neither baseline drug or alcohol use was associated with the subsequent risk of HF. Among black patients with incident HF, documented coronary artery disease was uncommon; no patients with HF had documentation of myocardial infarction and 8 of 9 who underwent coronary angiography had no or only mild evidence of coronary artery disease.
In multivariate analysis, each 10‐mm Hg increase in systolic BP doubled the risk of HF among black patients. By year 10, when participants were 28 to 40 years of age, 75% of black patients who eventually developed HF had hypertension compared with 12% in those in whom HF did not develop. In addition, 75% of black participants with hypertension were taking no antihypertensive medications upon entering the study, while another 9% were taking medication but did not have their BP controlled to <140/90 mm Hg. All black patients who developed incident HF had either untreated or poorly controlled BP at baseline. At year 10, 57% of black participants with hypertension were still not taking any antihypertensive medications and another 19% had poorly controlled BP despite the use of medications. Overall, among black patients with incident HF, 87% had untreated or poorly controlled BP at year 10.
Among patients aged 18 to 30 years at baseline, the incidence of HF during the next 20 years was much more common among black than white Americans and was closely associated with poorly treated hypertension, obesity, diabetes, and the presence of renal disease. The study highlights the potential for preventing HF through interventions that decrease the prevalence of obesity and more effectively addresses the development and treatment of hypertension.—Bibbins‐Domingo K, Pletcher MJ, Lin F, et al. Racial differences in incident heart failure among young adults. New Engl J Med. 2009;360 (12):1179–1190.
Comment
Observational studies in older patients, including the Framingham Heart Study, have shown that age, coronary ischemia, and hypertension are important risk factors for developing clinical HF. While the present data from this observational study suggest that HF is relatively uncommon in younger individuals, with a 20‐year incidence of only 0.5% for patients aged 18 to 20 years at baseline, the report also demonstrates that the interaction of these risk factors with HF may be different in younger patients based on ethnicity. The CARDIA data suggest that in people 18 to 30 years of age, over the next 20 years, (1) HF is much more likely to develop in black than white Americans, (2) coronary ischemia is a rare contributing factor for developing HF in this population, and (3) hypertension, and in particular untreated or poorly controlled hypertension, is the major risk factor for HF development in younger black Americans. Strengths of the CARDIA study include its large sample size, long follow‐up, exceptional retention rate during the entire 20‐year study period, careful adjudication of end points, and inclusion of a racially diverse and sex‐balanced population.
While an observational study such as CARDIA can reveal associations and cannot prove causation, it is interesting to hypothesize about the mechanism behind these provocative findings, particularly the increased incidence of HF among young black compared with young white participants. Self‐identified race is certainly a poor surrogate for genotype, but the fact that the CARDIA study demonstrated a greater than 20‐fold increase in the incidence of HF among black Americans compared with white Americans strongly suggests that race is a major risk factor for the development of HF in young persons, especially those with hypertension. Whether this is the result of underlying racial differences in the pathophysiology of HF and hypertension or environmental issues leading to inadequate risk factor (especially BP) control will continue to be debated. It is likely that both are involved. Of note, blacks are generally less likely than whites to be screened, receive treatment, or reach targeted goals for hypertension, dyslipidemia, and diabetes. Interestingly, baseline BP in the black cohort was nearly identical to that of the white cohort. However, BP during the course of the study is not reported. If BP were better controlled in white patients over the course of the study, that could certainly account for some of the differences noted in the incidence of HF. In fact, 87% of black patients who eventually developed HF exhibited either untreated or inadequately controlled BP 10 years into the trial. While the CARDIA trial is not an intervention study, lack of BP control is a major target for intervention to prevent HF, especially in young black men. While black CARDIA patients with hypertension at baseline had a 5.6% incidence of HF over the next 20 years, the incidence was only 0.8% in black patients without hypertension. Rather than wait for an intervention trial, these results are a call to action to screen and effectively treat hypertension and prevent obesity in young African Americans. Health professionals must continue to break down barriers that stand in the way of improved risk factor modification, especially BP control, in this population.