Total and cause-specific mortality in the cardiovascular health study

Abstract

Background: Few cohort studies have adequate numbers of carefully reviewed deaths to allow an analysis of unique and shared risk factors for cause-specific mortality. Shared risk factors could be targeted for prevention of premature death and the study of longevity.

Methods: A total of 5,888 community-dwelling persons aged 65 years or older living in four communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up was 16 years. Total and cause-specific mortality, including cardiovascular disease, stroke, cancer, dementia, pulmonary disease, infection, and other cause, were examined as outcomes. Variables previously associated with total mortality were examined for each cause of death using Cox proportional hazard models.

Results: Multiple risk factors were related to total mortality. When examining specific causes, many factors were related to cardiovascular death, whereas fewer were related to other causes. For most causes, risk factors were specific for that cause. For example, apolipoprotein E epsilon4 was strongly associated for dementia death and forced vital capacity with pulmonary death. Age, male sex, markers of inflammation, and cognitive function were related to multiple causes of death.

Conclusions: In these older adults, associations of risk factors with a given cause of death were related to specific deficits in that same organ system. Inflammation may represent a common pathway to all causes of death.

Figure 1.

Comparison of survival curves in Cardiovascular Health Study (solid lines) compared with U.S. census (dotted lines), 1990, by gender and race with age at death for the 25th, 50th, and 75th percentile. Gender difference in age at death: log-rank test X² = 172, p < .0001. Race difference in age at death: log-rank test stratified by gender: X² = 5.3, p = .0217. In women: X² = 4.6, p = .03, in men: X² = 4.1, p = .04.

Figure 2.

Hazard ratios for each cause of death by risk factor: (A) age, (B) weight, (C) forced vital capacity (D) creatinine (E) interleukin-6 (IL-6), (F) Digit Symbol Substitution Test (DSST) score. All models included the risk factors shown in Table 2 for total mortality. CVD = cardiovascular disease.

Figure 3.

Hazard ratios for risk factors by each cause of death: (A) cardiovascular excluding stroke, (B) stroke, (C) cancer, (D) dementia, (E) pulmonary (F) infectious, (G) other causes. AAI = ankle arm index; CHD = coronary heart disease; CHF = congestive heart failure; FVC = forced vital capacity; interleukin-6 = IL-6, DSST = Digit Symbol Substitution Test.