A total of 1025 decedents (mean age 79±11 years, 526 women) with HF were examined, of whom 900 were Original cohort and 125 were Offspring cohort participants. Examination of participant characteristics (shown in ) revealed that cardiovascular deaths were of high prevalence with or without prior MI. An underlying cause of death was identified (or deemed unknown) in all decedents. Characteristics of participants with or without LVEF assessment are shown in . Although those without LVEF assessment were younger, they were also more likely to die of cardiovascular causes. LVEF measurements were performed increasingly over time, with 24.9% (1980-1989, n=555), 92.6% (1990-1999, n=349), and 99.2% (2000-, n=121) of patients undergoing the study. Of the subsample with detailed death review, 463 decedents (mean age 82.2±9.3 years, 239 (52%) women) had LVEF assessed, of which 369 were Original cohort and 94 were Offspring participants, and 272 (59%) had HFREF. Evaluation of LVEF was performed temporally close to the HF onset date: 0.08±0.59 days for those evaluated after (n=399, 86.2%) and 0.36±0.70 days for those evaluated before HF onset date (n=64, 13.8%). A detailed diagram of the study cohort is shown in . A total of 1144 contributing causes were identified in 317 participants, with 2 to 7 contributing factors (mean 3.6) per participant, since more than one contributing condition could be attributed to each participant. Over 60% of deaths occurred in a hospital setting.
Description of Decedents With HF
Characteristics of Decedents With or Without LVEF Measured
Figure 1 Study cohorts available for death review. Primary death reviews for underlying cause of death were conducted in the largest HF cohort (n=1025). Detailed death reviews for underlying, immediate, and contributing causes of death were conducted in those (more ...)
Classification of Cause of Death
The categorization of underlying and immediate causes of death into cardiovascular (e.g., CHD, stroke) or noncardiovascular disease categories is shown in . Overall, 62% of underlying causes of death were cardiovascular, with a large proportion (25%) of underlying causes attributable to CHD. Progressive pump failure was the major non-CHD cause of cardiovascular death (16% of all underlying causes). Respiratory disease (infectious and noninfectious) was the leading underlying cause of noncardiovascular death (10%), followed by cancer (9%).
Cause of Death in Overall Cohort
Overall, 46% of immediate causes of death were cardiovascular, with the majority attributable to non-CHD cardiovascular disease. The leading immediate cardiovascular causes of death overall were progressive pump failure (24%) and arrhythmia or sudden cardiac death (15%). The leading noncardiovascular causes of death were infectious/noninfectious respiratory disease (17%), and other systemic infections (8%).
Underlying Causes of Death by LV Systolic Function
For the subset with available LVEF, the underlying causes of death for those with systolic dysfunction or preserved systolic function are shown in . Cardiovascular death was the predominant underlying cause of death in those with HFREF, representing 76% of deaths in men and 70% in women. In contrast, cardiovascular conditions represented a smaller proportion of the underlying causes of death in those with HFPEF, with 39% of deaths in men and 49% in women attributed to a cardiovascular cause.
Underlying Causes of Death in HFREF vs. HFPEF
Classification of Immediate Causes of Death by LV Systolic Function
Classification of immediate causes of death according to LVEF status is shown in . Although most with HFREF died from cardiovascular death (55%), other cardiovascular disease etiologies were the most important reasons for cardiovascular death. In those with HFPEF, cardiovascular causes were responsible for only 34% of immediate causes of death. Among the ‘other cardiovascular disease’ etiologies, progressive HF and arrhythmia or sudden cardiac death were the predominant factors leading immediately to death. In those with HFREF, cardiovascular deaths accounted for 20.4% and 18.5% of all deaths in men and women, respectively. In HFPEF, 23.2% of men and 11.7% of women died due to immediate cardiovascular causes.
Immediate Causes of Death in HFREF vs. HFPEF
Predictors of Cardiovascular Disease as the Underlying Cause of Death
Results of sex-specific adjusted analyses are shown in . Increased age at death was associated with greater odds of noncardiovascular death in both sexes. In men, prior MI was not associated with cardiovascular versus noncardiovascular death. In women, however, prior MI was associated with increased risk of cardiovascular disease as the underlying cause of death, with an odds ratio of 1.87 (95% CI 1.10, 3.16).
Predictors of Cardiovascular (vs. Noncardiovascular) Underlying Cause of Death
In women, there was a significant decrease in the odds of cardiovascular disease as the underlying cause of death in those with HF in the latter (post-1980) compared to earlier (pre-1980) time period, with an odds ratio of 0.41 (95% CI 0.24, 0.69). In men, the decline in the odds of cardiovascular disease as the underlying cause of death was of borderline statistical significance. Although mean age at death was higher post-1980 than pre-1980 (81.7±9.6 vs. 70.3±9.5 years), this did not fully explain the trend, since the aforementioned odds ratios were age-adjusted. The presence of LV systolic dysfunction was a strong predictor of cardiovascular disease as an underlying cause of death, conferring more than a 3-fold risk in men and greater than 2-fold risk in women with HFREF (see ).
Predictors of Cardiovascular Disease as the Immediate Cause of Death
Sex-specific adjusted analyses demonstrated that prior MI did not predict an immediate cause of death that was cardiovascular (). Instead, presence of HFREF was the most significant predictor of an immediate cause of death that was cardiovascular with a nearly 5-fold risk in men and greater than 2-fold risk in women. Predicted probabilities of total cardiovascular death are shown in the Supplemental Table
, demonstrating higher probabilities of cardiovascular death in younger patients, with prior MI, and HFREF.
Predictors of Cardiovascular (vs. Noncardiovascular) ‘Immediate’ Cause of Death
Contributing Causes of Death
The most frequent contributing causes of death stratified by LVEF are shown in . After pump failure, ischemic and valvular heart diseases were the most important cardiac contributors to death irrespective of LV systolic function status. Renal disease, diabetes, and noninfectious respiratory conditions were the most common noncardiovascular contributors.
Leading conditions contributing to death in HF