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. Author manuscript; available in PMC: 2020 Sep 11.
Published in final edited form as: Circ Heart Fail. 2019 Sep 11;12(9):e005730. doi: 10.1161/CIRCHEARTFAILURE.118.005730

Prevalence of American Heart Association Heart Failure Stages in African-American and White Young and Middle Aged Adults: The CARDIA Study

Samuel S Gidding 1, Donald Lloyd-Jones 2, Joao Lima 3, Bharat Ambale-Venkatesh 3, Sanjiv J Shah 4, Ravi Shah 5, Cora E Lewis 6, David R Jacobs Jr 7, Norrina B Allen 2
PMCID: PMC6741433  NIHMSID: NIHMS1535979  PMID: 31505940

Abstract

Background

Staging criteria for heart failure range from Stage 0 (without risk) to being at risk (Stage A) to presence of cardiac structural/functional abnormalities (Stage B) to symptomatic/end stage (Stages C/ D). There is limited data on the prevalence of these stages in early adulthood and predictors of heart failure stage and symptoms in middle age.

Methods: and Results

The CARDIA study, a cohort of generally healthy black and white men and women, collected phenotypic, echocardiographic, and outcomes data at the years 5 and 30 examinations when participants were 22–37 and 47–62 years. Prevalence of heart failure stages were calculated and relationship of year 5 stage to year 30 classification and outcomes was assessed. At year 5, 2189 participants had complete data. Prevalence of heart failure stage A/B increased from 24% to 76% in African-American men, from 13% to 64% in white men, from 34% to 81% in African-American women, and from 13% to 56% in white women. African-Americans were more likely to be in any stage or with morbidity at both time points because of higher risk factor prevalence. Of 33 participants with heart failure or heart failure deaths by year 30, 21 (64%) had been in Stage A or B at year 5. Only 6 participants at year 5 in Stage A (at risk) improved risk status at year 30.

Conclusions

Risk for heart failure increased in participants from 1990 (age 22–37) to 2015 (age 47–62). Symptomatic heart failure or death from heart failure is associated with heart failure stage at age 22–37 years. African-Americans are disproportionately affected.

Keywords: Aging, Race and Ethnicity, Risk Factors, Heart Failure, Echocardiography


Prevalence of heart failure is increasing in the United States, particularly in African-Americans and those above 60 years of age. 1The American Heart Association and American College of Cardiology (AHA/ACC) have established staging criteria for heart failure ranging from not being at risk (Stage 0) to being at risk (Stage A) to presence of cardiac structural or functional abnormalities (Stage B) to symptomatic heart failure (Stages C and D).2 The pre-symptomatic stages (A and B) predict incident heart failure in middle-aged and older individuals. 35 Heart failure may be the first manifestation of acquired cardiovascular disease, particularly in African-Americans. 6 There is limited information on the antecedents of these stages and on prevalence in African-Americans, especially before middle age. The Coronary Artery Risk Development in Young Adults study (CARDIA) has collected both phenotypic and echocardiographic data at age 22–37 years (exam Year5) and at age 47–62 years (exam Year 30) in White and African-American men and women to allow assessment of the antecedents and progression of heart failure stages.

The objectives of this paper are to 1) estimate the prevalence of heart failure stages by race and gender in the CARDIA cohort at the year 5 examination when participants were 22–37 years of age to assess evolution of heart failure stages over time, 2) determine the prevalence of heart failure stages by race and gender in the CARDIA cohort at the year 30 examination when participants were 47–62 years of age, and 3) compare characteristics of the cohort (year 5) by heart failure stage at year 30. We hypothesized that the prevalence of more advanced heart failure stages would increase over time, African-Americans would be more adversely affected, and obesity would be associated with prevalence of later stages of HF.

Methods

CARDIA is a longitudinal epidemiologic study initiated in 1985–86 with a primary goal of understanding the evolution of cardiovascular risk factors beginning in young adulthood using a population-based healthy cohort stratified by sex, race (African-American/Caucasian), and education (above and below a high school education). 7 Examinations have been conducted at years 0, 2, 5, 7, 10 and every 5 years thereafter at 4 field centers located in Chicago IL, Birmingham AL, Oakland CA, and Minneapolis MN. Research protocols have been approved by local IRBs and informed consent has been obtained from all participants at each examination. A single coordinating center at the University of Alabama, Birmingham has supervised data collection. Data for this paper were primarily obtained from the years 5 and 30 examinations, when echocardiograms were obtained.7, 8 Information regarding gaining access to CARDIA data can be found at the CARDIA website. 9

Heart failure stages were defined according to the 2013 AHA/ACC guidelines that classified HF into progressive stages: stage 0 without risk, stage A, HF risk factors; stage B, asymptomatic cardiac structural or functional abnormalities; stage C, symptomatic or stage D, end-stage HF (Table 1). 2 In this analysis, stage C and D were combined because of small sample size. Criteria for defining components of Stages A through D follow. Hypertension was defined as systolic BP ≥140mmHg, or diastolic BP ≥90mmHg, or taking antihypertensive medication to be consistent with the original staging classification. Diabetes mellitus was defined as either fasting blood glucose ≥126 mg/dL, or taking diabetic medication. Obesity was defined as BMI ≥30kg/m2. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III as presence of three or more of the following components: waist circumference >102 cm in men and >88 cm in women, triglycerides ≥150 mg/dL, HDL-C <40 mg/dL in men and <50 mg/dL in women, BP ≥130/85 mm Hg or taking BP medication, and fasting glucose ≥100 mg/dL. 10 Atherosclerotic disease included in addition to adjudicated coronary heart disease (for stage B classification), carotid artery disease, non-MI acute coronary syndrome, peripheral artery disease. End stage renal disease was defined as requiring chronic dialysis therapy.9 Cardiac structural or functional abnormalities included: significant valvular disease (moderate or greater aortic or mitral stenosis, aortic or mitral regurgitation); presence of reduced LV ejection fraction was defined as <40%; LV hypertrophy was defined as LV mass indexed to BSA>95 g/m2 for women and >115 g/m2 for men (American Society of Echocardiography definitions of left ventricular hypertrophy and reduced ejection fraction). 11,12 Prevalent HF was based on adjudicated HF events. Criteria requiring a medical diagnosis (e.g. prior myocardial infarction, cancer, HIV, heart failure symptoms/diagnosis) were ascertained by CARDIA investigators’ review of relevant hospital records and laboratory studies.6,9 Information not available in the CARDIA data set was primarily information related to family history of cardiomyopathy. Stage 0 was determined by failure to satisfy any of the above criteria among those with sufficient non-missing information to make that judgment.

Table 1.

AHA/ACC Heart Failure Stages adapted to available CARDIA data

HF Stages AHA/ACC Guideline Description Operational Definition in this Study
Stage 0 No HF risk factors, no abnormal cardiac structure or function, no symptoms of HF
Stage A With at least 1 HF risk factor but without structural or functional abnormalities At least 1 of the following clinical risk factors: hypertension, diabetes, obesity, metabolic syndrome, atherosclerotic disease (adjudicated: coronary heart disease, carotid artery disease, non-MI acute coronary syndrome, peripheral artery disease) or end stage renal disease
Stage B With risk factors and presence of at least 1 structural or functional abnormalities but without signs or symptoms of HF At least 1 of the following cardiac structural or functional abnormalities: valvular heart disease, prior MI, abnormal LV ejection fraction, regional wall motion abnormality, LV hypertrophy based on LV mass indexed to BSA
Stage C/D Current or prior HF associated with structural or functional abnormalities plus signs or symptoms of HF Prevalent HF based on committee adjudicated HF events

AHA/ACC denotes American Heart Association/American College of Cardiology; HF, heart failure; BP, blood pressure; HDL, high-density lipoprotein; CHD, coronary heart disease; CAD, carotid artery disease; PAD, peripheral artery disease; ESRD, end stage renal disease; CAC, coronary artery calcium; MI, myocardial infarction; LV, left ventricular; BSA, body surface area

The cohort was assembled from those participating in the CARDIA year 5 examination. The method of cohort selection is provided in Figure 1. Descriptive statistics were calculated. The cohort used for the primary analyses was examined and had complete data for both time points. Descriptive statistics were calculated. Comparisons across groups were made by chi square or t-test as appropriate. Sensitivity analyses used data from the entire examined cohorts at year 5 and 30. These included recalculation of heart failure stage prevalence at year 30 after inverse probability weighting in order to address potential bias due to loss-to follow-up. Total cardiac and heart failure deaths were related to year 5 stage in the sensitivity analysis. Comparisons of the subgroup with stage B heart failure risk at year 5 for various associated traits including self-reported physical activity and total treadmill time at year 20 on a standardized exercise stress test.

Figure 1.

Figure 1

HF Stage Study Participant Flow Diagram

Results

For the primary analysis, 2189 CARDIA participants with complete data allowing classification of heart failure stage at both years 5 and 30 were included. The prevalence of each stage for the cohort as a whole, by age, and by race and sex at years 5 and 30 is presented in Figures 24. At year 5 just above 20% of the cohort was at risk for heart failure being in stage A or B with 13% of whites, 24% of African-American men, and 35% of African-American women at risk. At year 30, over two thirds of the cohort was at risk for heart failure (Stage A or B) while 1% had symptomatic heart failure. Prevalence of each stage was relatively constant within the CARDIA 13 year age range. African-Americans were far more likely to be at risk for heart failure (stages A or B) or have symptomatic heart failure than whites. Only about 20% of African-Americans were in Stage 0 at year 30 whereas white women were most likely to be in Stage 0.

Figure 2.

Figure 2

Prevalence of Heart Failure stages in study cohort (N=2189)

Figure 4.

Figure 4

Prevalence of Heart Failure (HF) stages in study cohort, by race-sex subgroup

Average risk factor levels in year 5 by heart failure stage in year 30 are presented in Table 2. Risk factor levels increase with each stage by definition, particularly hypertension, obesity and diabetes. Risk factors more common in those with symptomatic heart failure 25 years later were obesity, left ventricular hypertrophy, and decreased self-reported physical activity.

Table 2.

Year 30 and Year 5 Characteristics of Study Cohort by HF Stages at Year 30, CARDIA (1990–2015)

Year 30 HF Stages
Total (n=2189)
Healthy (n=676) Stage A (n=921) Stage B (n=572) Stage C/D (n=20) p-trend
Year 30 (2015) and Year 5 (1990) Characteristics
Female sex, % 58.0 56.5 54.9 45.0 0.19 56.4
African American, % 27.1 51.7 49.3 80.0 <.001 43.7
Education > HS, % 81.9 72.4 68.7 50.0 <.001 74.2
Y30 Age, y 55.2 (3.5) 55.2 (3.7) 55.1 (3.5) 57.0 (3.5)* 0.78 55.2 (3.6)
Y5 Age, y 30.1 (3.5) 30.1 (3.6) 30.0 (3.5) 32.1 (3.8) * 0.78 30.1 (3.5)
Y30 Body mass index, kg/m2 24.9 (2.9) 33.4 (6.8) 30.5 (7.1) 36.0 (9.9) <.001 30.0 (7.0)
Y5 Body mass index, kg/m2 22.5 (2.6) 27.2 (5.3) 26.0 (5.1) 30.0 (7.7) <.001 25.4 (5.0)
Y30 Obesity, % 0.0 72.3 44.9 75.0 <.001 42.8
Y5 Obesity, % 0.6 23.0 17.1 50.0 <.001 14.8
Y30 Current smokers, % 9.1 11.7 15.6 25.0 * <.001 12.0
Y5 Current smokers, % 18.7 25.1 25.0 30.0 <0.01 23.1
Y30 Physical activity score, activity units 406.7 (294.9) 277.1 (234.7) 321.7 (279.9) 176.0 (174.3) <.001 327.9 (271.9)
Y5 Physical activity score, activity units 431.5 (308.1) 355.4 (279.0) 399.3 (302.3) 266.2 (200.3) * 0.01 389.6 (295.7)
Y30 Systolic BP, mm Hg 112.0 (11.6) 122.9 (15.3) 125.2 (19.2) 127.7 (19.6) <.001 120.2 (16.4)
Y5 Systolic BP, mm Hg 103.0 (9.1) 108.5 (10.8) 108.2 (10.4) 109.4 (10.5) <.001 106.8 (10.5)
Y30 Diastolic BP, mmHg 67.9 (8.7) 76.3 (9.7) 75.7 (12.5) 76.2 (13.0) <.001 73.6 (10.9)
Y5 Diastolic BP, mmHg 65.4 (8.2) 69.8 (9.5) 70.1 (9.6) 71.2 (8.6) <.001 68.6 (9.4)
Y30 Hypertension, % 0.0 54.4 45.6 85.0 <.001 35.6
Y5 Hypertension, % 0.3 4.0 4.5 5.0 * <.001 3.0
Y30 Antihypertensive medication, % 0.0 43.9 35.3 80.0 <.001 28.4
Y5 Antihypertensive medication, % 0.1 1.2 * 1.6 * 0.0 0.02 1.0
Y30 Total cholesterol, mg/dL 197.4 (35.8) 189.0 (38.3) 188.7 (37.5) 165.6 (41.4) <.001 191.3 (37.6)
Y5 Total cholesterol, mg/dL 171.6 (30.2) 179.8 (33.5) 179.6 (32.6) 189.2 (30.9) * <.001 177.3 (32.5)
Y30 HDL cholesterol, mg/dL 66.1 (17.6) 55.5 (17.2) 59.4 (19.0) 52.9 (14.4) <.001 59.8 (18.3)
Y5 HDL cholesterol, mg/dL 57.1 (12.9) 51.9 (13.4) 53.8 (14.2) 50.4 (14.9) * <.001 54.0 (13.6)
Y30 Lipid-lowering medication, % 5.9 23.7 20.1 35.0 <.001 17.4
Y5 Lipid-lowering medication, % 0.4 0.2 0.2 0.0 0.35 0.3
Y30 Fasting glucose, mg/dL 91.5 (8.3) 107.9 (35.3) 104.2 (31.0) 104.7 (21.3) * <.001 101.8 (29.2)
Y5 Fasting glucose, mg/dL NA NA NA NA NA NA
Y30 Diabetes, % 0.0 19.9 14.7 30.0 <.001 12.5
Y5 Diabetes, % 0.0 0.1 0.5 0.0 0.06 0.2
Y30 Diabetes medication, % 0.0 15.7 11.4 20.0 <.001 9.8
Y5 Diabetes medication, % 0.0 0.1 0.5 0.0 0.06 0.2
Y30 Metabolic syndrome, % 0.0 42.7 31.8 50.0 <.001 26.7
Y5 Metabolic syndrome, % 0.0 2.6 4.0 0.0 <.001 2.1
Y30 LV mass index, g/m2 76.2 (14.7) 79.1 (14.4) 100.8 (27.0) 115.6 (41.4) <.001 84.2 (21.7)
Y5 LV mass index, g/m2 75.9 (18.4) 76.5 (17.7) 81.7 (18.3) 91.3 (19.5) <.001 77.8 (18.3)
Y30 LV hypertrophy, % 0.0 0.0 53.1 60.0 <.001 14.4
Y5 LV hypertrophy, % 3.0 2.6 9.1 15.0 <.001 4.5
Y30 LV ejection fraction, % 64.4 (6.0) 65.1 (6.2)* 61.2 (8.8) 49.5 (16.0) <.001 63.7 (7.4)
Y5 LV ejection fraction, % 72.8 (7.0) 73.3 (7.0) 72.1 (7.9) 70.1 (9.8) <.001 72.8 (7.3)
Y30 Low LV ejection fraction, % 0.0 0.0 22.2 45.0 <.001 6.2
Y5 Low LV ejection fraction, % 0.0 0.0 1.7 10.0 <.001 0.5
Y30 History of atherosclerotic disease, % 0.0 1.4 5.2 20.0 <.001 2.1
Y5 History of atherosclerotic disease, % 0.0 0.0 0.0 0.0 NA 0.0
Y30 History of CRV, % 0.0 0.9 3.5 10.0 <.001 1.4
Y5 History of CRV, % 0.0 0.0 0.0 0.0 NA 0.0
Y30 History of MI, % 0.0 0.0 4.2 15.0 <.001 1.2
Y5 History of MI, % 0.0 0.0 0.0 0.0 NA 0.0
Y30 History of HF, % 0.0 0.0 0.0 100.0 0.02 0.9
Y5 History of HF, % 0.0 0.0 0.0 0.0 NA 0.0

Values are mean (SD), or %. Abbreviations: HF, heart failure; BP, blood pressure; HDL, high-density lipoprotein; LV, left ventricular; HIV, human immunodeficiency virus; HD, heart disease; MI, myocardial infarction; CRV, cardiac revascularization; NA, not available.

HF stages: 0, healthy; A, HF risk factors; B, asymptomatic cardiac structural or functional abnormalities; C/D, HF associated with structural or functional abnormality plus symptoms.

*P<0.05, †P<0.01, ‡P<0.001 compared to reference category (Healthy).

Risk factors at year 30 by heart failure stage are also reported in table 2. About three quarters of those in stage A and Stage C/D were obese and 44% of those in stage B were obese. Those at risk for heart failure at year 30 had lower self-reported physical activity than those not at risk and average fasting glucose was above 100 mg/dl. Lower educational attainment was associated with heart failure and change in Stage. Of those in Stage C/D, 80% were African-American. All cardiovascular risk factors except for lipids had high prevalence. Interestingly, lipids declined substantially in those with symptomatic heart failure at year 30 compared to values at year 5. Supplemental Table 1 shows risk factor data by heart failure stage at year 30 by race and gender. Whites were more likely to be in Stage 0 and there were only 4 white participants in stage C/D. Though quantitatively different by race and gender the trends reported above remained similar across all 4 groups.

Table 3 presents a cross-tabulation of heart failure stage at year 5 with heart failure stage at year 30 by ethnicity. For the entire cohort, 62 % of those in stage 0 at baseline progressed to Stage A, B, or symptomatic heart failure. African-Americans were more likely to be in any stage or with morbidity at both time points because of higher risk factor prevalence. At year 5 for Stage A (at risk) only 6/345 (1.7%) changed status at year 30. African-Americans were much more likely to move to an advanced heart failure stage. The presence of Stage A or B at year 5 was significantly associated with incident symptomatic heart failure with 13/20 incident events occurring in the 21% of the cohort in Stage A or B at year 5. This trend was particularly true for African-Americans whereas for whites, all incident stage C heart failure occurred in those in Stage 0 at year 5.

Table 3.

25 year Changes in Prevalence of Heart Failure Stages (1990–2015) – Sensitivity Analysis, using EF<40% rather than <53%

Year 5 HF Stage Overall Year 30 HF Stage, N (%)

N (% of total) 0 A B C/D
All 2189
0 1733 (79.2) 679 (39.2) 695 (40.1) 352 (20.3) 7 (0.4)
A 351 (16.0) 7 (2.0) 247 (70.4) 88 (25.1) 9 (2.6)
B 105 (4.8) 22 (21.0) 28 (26.7) 51 (48.6) 4 (3.8)

African-American 957
0 659 (68.9) 183 (27.8) 325 (49.3) 148 (22.5) 3 (0.4)
A 246 (25.7) 5 (2.0) 163 (66.3) 69 (28.0) 9 (3.7)
B 52 (5.4) 6 (11.5) 13 (25.0) 29 (55.8) 4 (7.7)

White 1232
0 1074 (87.2) 496 (46.2) 370 (34.5) 204 (19.0) 4 (0.4)
A 105 (8.5) 2 (1.9) 84 (80.0) 19 (18.1) 0 (0.0)
B 53 (4.3) 16 (30.2) 15 (28.3) 22 (41.5) 0 (0.0)

Interestingly, many participants in Stage B changed to Stage A or Stage 0 (typically by improvement in left ventricular mass or ejection fraction). Changes in left ventricular mass or ejection fraction in those whose status improved to Stage 0 often reflected small changes in those variables (within 10% of the baseline value). By definition this group did not have risk factors associated with Stage A. (Table 4) Secondary analyses looking at self-reported physical activity and endurance on treadmill testing at other CARDIA examinations were not different in those who went from Stage B to Stage 0.

Table 4.

Differences in Cardiovascular Risk Factors and Selected Year 30 Characteristics by ΔHF Stage Groups

Risk Factors Stage 0 N=650 Improved N=53 Stable N=298 Worsened N=1168 Developed HF N=20
Age, y 55.2 (3.5) 55.3 (3.3) 55.5 (3.6) 55.0 (3.6) 57.0 (3.5)
Female sex, % 57.4 71.7 61.4 54.1 45.0
African American, % 26.9 37.7 64.8 47.3 80.0
Education > HS, % 82.5 67.9 64.4 72.8 50.0
25-y difference (year 30 – year 5)
 Body mass index, kg/m2 2.5 (2.5) 3.5 (5.5) 5.2 (6.0) 5.6 (4.9) 6.0 (5.7)
 Physical activity score, activity units −24.4 (285.4) −46.3 (243.1) −90.8 (288.1) −74.0 (283.5) −90.2 (122.9)
 Systolic BP, mm Hg 9.2 (11.8) 7.7 (16.5) 12.6 (19.3) 16.1 (17.4) 18.3 (18.7)
 Diastolic BP, mmHg 2.7 (9.9) 3.1 (14.0) 2.5 (14.0) 7.0 (12.6) 5.0 (11.5)
 Total cholesterol, mg/dL 26.2 (32.3) 23.5 (31.8) −2.5 (42.4) 11.7 (41.1) −23.6 (37.4)
 HDL cholesterol, mg/dL 9.0 (13.9) 5.3 (15.3) 6.3 (12.7) 4.0 (13.6) 2.4 (10.4)
 LV mass index, g/m2 1.9 (15.4) −38.0 26.2) 2.4 (19.5) 11.7 (24.0) 24.3 (41.1)
 LV ejection fraction, % −8.4 (8.5) −6.0 (9.8) −8.5 (10.0) −9.4 (8.8) −20.5 (19.1)
Year 30
 Obesity, % 0.0 39.6 80.9 56.6 75.0
 Current smokers, % 8.9 21.1 11.3 13.4 25.0
 Hypertension, % 0.0 18.9 59.7 49.1 85.0
 Antihypertensive medication, % 0.0 15.1 51.3 38.1 80.0
 Lipid-lowering medication, % 6.0 7.5 29.5 20.7 35.0
 Diabetes, % 0.0 3.8 33.2 14.2 30.0
 Diabetes medication, % 0.0 1.9 27.5 10.9 20.0
 Metabolic syndrome, % 0.0 18.9 51.0 35.4 50.0
 LV hypertrophy, % 0.0 0.0 14.1 22.4 60.0
 Low LV ejection fraction, % 0.0 0.0 7.0 9.1 45.0
 History of atherosclerotic disease, % 0.0 0.0 3.0 2.9 20.0
 History of CRV, % 0.0 0.0 2.0 1.9 10.0
 History of MI, % 0.0 0.0 1.0 1.8 15.0
 History of HF, % 0.0 0.0 0.0 0.0 100.0

Values are mean (SD), or %. Abbreviations: HF, heart failure; BP, blood pressure; HDL, high-density lipoprotein; LV, left ventricular; MI, myocardial infarction; CRV, cardiac revascularization; NA, not applicable; HS, high school

Sensitivity analyses performed with the excluded cohort showed the excluded sample had more men, more African-Americans and worse risk status for all risk factors except lipids (Supplemental Table 2). The excluded cohort had higher LV mass at year 5 and was more likely to have low ejection fraction (p<0.001). Weighted probability analysis results were similar to those reported above and suggested results reported above are slight underestimates based on the higher prevalence of risk in the excluded cohort (Supplemental Table 3). A further sensitivity analysis looked at the relationship of all cardiac and heart failure deaths to heart failure stage at year 5. Of 3448 eligible participants, 2594 (75.2%) were stage 0, 640 (18.6%) were stage A, and 214 (6.2%) were Stage B. Per cent all cause cardiac mortality by stage was 1½594 (0.4%), 12/640 (1.9%), and 5/214 (2.3%) and heart failure mortality was 7/2594 (0.3%), 4/640 (0.6%), and ½14 (0.5%). These numbers were too small for statistical analysis but showed a trend relating increased likelihood of cardiac death to heart failure stage at year 5.

Discussion

In the racially diverse CARDIA cohort followed for 25 years with careful cardiovascular phenotyping, by ages 47–62 years old the majority of participants were at risk for heart failure. African-Americans have a higher prevalence of risk than whites. Similarly, African-Americans have a higher prevalence of symptomatic heart failure. These results are consistent with analyses among middle-aged, community-dwelling individuals in Olmsted County, the Framingham Heart Study and ARIC study.35 In 1990, at ages 22–37, the prevalence of heart failure stages A and B was much lower in this cohort. However about two thirds of future heart failure cases and deaths come from those in stage A or stage B, about 20–25% of the year 5 cohort. A trend towards total cardiac mortality during the 25 year follow up also was related to heart failure stage at year 5. Prior CARDIA analyses have shown the higher likelihood of African-Americans to develop heart failure in young adulthood/early middle age and the importance of cardiac structural measures in predicting future cardiovascular events. 6, 13, 14 Estimates in this study are likely lower than actual prevalence in the general population as shown by our weighted probability sensitivity analysis, based on risk present in the cohort not evaluable at year 30. Beyond the criteria provided in the ACC/AHA classification system, these data emphasize the importance of tobacco use, relatively low self-reported physical activity, and African-American race to identify individuals who may be at risk in young adulthood and early middle age, since these characteristics were associated with heart failure risk in year 5 and symptomatic heart failure/deaths at year 30.

Three cohort studies have looked at the prevalence of heart failure stages. In the Framingham Heart Study, with a cohort of average age of 51 years similar to this study, Xanthakis et al showed a prevalence of stage A of 36.5% and stage B of 24.2 % with increasing prevalence with increasing age.4 Biomarkers related to heart failure were associated with stage A and B. Methodology was similar to this study. In Olmsted County, Minnesota, a cohort of individuals with median age above 60 years (age range 45 to > 75 years) had a prevalence of stage A of 22%, of Stage B 34% and stages C and D 12%.5 Five year survival and brain natriuretic peptide levels were directly related to heart failure stage. Determination of cardiac structural abnormalities included electrocardiographic criteria for LV hypertrophy, a qualitative definition of diastolic dysfunction, and different critieria for assessing LV cavity size than in this study. These cohorts are predominantly Caucasian. In the ARIC study of African-Americans and whites with a median age of 75 years (range 66 to 90 years), Shah et al showed that only 5 % of the cohort was without heart failure risk. 3 Stage A prevalence was 52%, Stage B 30% and 13% had symptomatic heart failure. Longitudinal analyses showed that both echocardiographic criteria included in the stage B classification and newer measures such as speckle tracking echocardiography improved the ability to risk stratify. ARIC used study specific criteria for cardiac structure and function abnormalities because of the older age of the cohort. In a separate ARIC analysis, physical activity and change in physical activity have been associated with incident heart failure. 15 The Jackson Heart Study showed cigarette smoking was associated with incident heart failure.16 We have shown in the CARDIA study that left ventricular mass has a modest effect on cardiovascular risk reclassification based on the Framingham Heart Study risk equation. 13

Observations from long term observational studies have consistently linked risk exposures in adolescence and young adulthood to subclinical cardiovascular outcomes decades later in young adulthood and middle age. A consistent finding across CARDIA analyses is that risk identified in young adulthood predicts subclinical outcomes such as left ventricular hypertrophy, adverse left ventricular structure, adverse changes in cardiac function, and presence of coronary artery calcium 15–25 years hence.1720 In this cohort and the MESA cohort, Liu et al have shown that treatment of elevated blood pressure to lower levels does not restore subclinical disease burden or incident clinical disease risk to the same level as individuals whose blood pressure was always at the lower level.21 This failure may be in part related to chronic exposure prior to initiation of treatment. Several cohorts with participants followed from adolescence and with subclinical cardiovascular measures in young adulthood show strong relationships of adolescent risk to adult subclinical cardiac structure and function as well as carotid intima media thickness.2224

These analyses suggest two opportunities to lower the prevalence of heart failure stages A through D, later in life. The first is obesity prevention or treatment. The presence of obesity and obesity-related co-morbidities, diabetes and hypertension, drive the high prevalence of Stage A and contribute to stage B classification, cardiac structural abnormalities and prevalent atherosclerosis in the CARDIA cohort. 17, 25 The second is earlier recognition of treatable risk factors, particularly hypertension and smoking. 26, 27 Several studies have shown that treatment of hypertension lowers risk of incident heart failure. In this study, essentially no one improved from Stage A to Stage 0 status over 25 years of follow up.26 Observational studies support adherence to healthy lifestyle and risk factor control are associated with lower future event rates. In men, women and across ethnicities.2830

Cardiovascular disease mortality rates in middle aged adults are not declining, particularly in women. 31 Part of this failure to impact cardiovascular disease mortality rates appears attributable to the obesity epidemic.31 The CARDIA cohort was recruited around the onset of the obesity epidemic; secular trends in prevalence of obesity likely contribute to the development of increased heart failure risk during follow up. 32 A second cause may be the absence of an evidence base for treatment in vulnerable 20–50 year olds. The absence of clinical trial data contributes to low evidence grades regarding efficacy of true preventive therapy for high risk individuals and low awareness among clinicians of the need for early management of risk factors. Trials powered to have events as endpoints require high risk populations with events likely to occur within 5 years of trial initiation, otherwise the cost of conducting the trials would be prohibitive. This creates a bias against recognition of younger individuals with lower short term risk but high lifetime risk. For example, currently only 28% of adults below the age of 50 years who meet entry criteria for the SPRINT clinical trial currently receive anti-hypertensive medication according to NHANES data. 27 Data from CARDIA and other longitudinal studies suggest that high risk younger adults can be identified for clinical trials. Valid end points for these studies might be both events and improvement in structural and functional cardiac abnormalities.

Though a high percentage of those with stage B classification at year 5 went on to develop heart failure or died related to heart failure, about one third of those in stage B improved to Stage 0 over 25 years. The typical profile of the person who changed status was the absence of cardiovascular risk factors, particularly obesity, at year 5 and year 30 but a change secondary to either LV mass or LV ejection fraction being within 10% of the thresholds for classification. This change is consistent with the measurement error observed from quality control analyses at the echocardiography reading center.8 Thus, caution should be used in the clinical setting in over-interpreting borderline values for ejection fraction or left ventricular mass in the absence of other heart failure risk factors.

An important limitation of this study is the lack of data on those CARDIA participants not examined at year 30. Follow up with over 90% of the cohort is achieved every 6 months by telephone even those not attending examinations. Important medical events occurring in the interval may be missed. Event ascertainment may be incomplete and the interval between echocardiograms was 25 years. Our sensitivity analysis reviewing risk status of the excluded cohort suggested actual heart failure events in the full cohort occurred at slightly higher frequency than the cohort examined in detail. Prevalence estimates may be different for other race/ethnic groups than African-Americans and whites.

In summary we have confirmed that many middle-aged United States African-Americans and whites are at risk for heart failure, with African-Americans at highest risk. Prevalence of heart failure stages increases dramatically from young adulthood in this cohort of participants born 1954–1967, when about 13% of whites and 30% of African Americans are at risk. The majority of incident heart failure events occur in those in heart failure stage A or B at a young age with those in Stage 0 being at low risk. Tobacco use and low self-reported physical activity may add information to the current staging system. Opportunities for prevention abound.

Supplementary Material

Supplemental Material

Figure 3.

Figure 3

Prevalence of Heart Failure (HF) stages in study cohort, by age category

What is New

  • Onset of heart failure by middle age is strongly associated with AHA/ACC risk stage at age 23–35 years.

  • Risk for heart failure increases dramatically between 23–35 years of age and 48–60 years of age.

  • African-Americans are disproportionately affected.

  • Tobacco use and low self-reported physical activity may also be associated with progression of heart failure stage

Clinical Implications

  • Prevention of heart failure will require improved control of risk factors, particularly obesity and hypertension, at a young age.

  • African-Americans should receive particular attention.

Acknowledgments

Sources of Funding

The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), University of Minnesota (HHSN268201800006I), and Kaiser Foundation Research Institute (HHSN268201800004I). This manuscript has been reviewed by CARDIA for scientific content.

Footnotes

Disclosures

No authors have conflicts of interest for this ms.

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