Background-Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. Methods and Results-We evaluated 676 Framingham Heart Study participants between 45 and 85 years of age (mean age 67 years, 34% women) who developed a first MI between 1970 and 1999. We assessed the incidence rates of heart failure and of death without heart failure in each of 3 decades (1970 to 1979, 1980 to 1989, and 1990 to 1999). We estimated the multivariable-adjusted risk of events in the latter 2 decades, with the period 1970 to 1979 serving as the referent. The 30-day incidence of heart failure after MI rose from 10% in 1970 to 1979 to 23.1% in 1990 to 1999 (P for trend 0.003), whereas 30-day mortality after MI declined from 12.2% (1970 to 1979) to 4.1% (1990 to 1999).The 5-year incidence of heart failure after MI rose from 27.6% in 1970 to 1979 to 31.9% in 1990 to 1999 (P for trend 0.02), whereas 5-year mortality after MI declined from 41. 1% (1970 to 1979) to 17.3% (1990 to 1999). In multivariable analyses, compared with the period 1970 to 1979, we observed higher 30-day (risk ratio 2.05, 95% confidence interval 1.25 to 3.36) and 5-year (risk ratio 1.74, 95% confidence interval 1.07 to 2.84) risks of heart failure in the decade 1990 to 1999. These trends were accompanied by lower 30-day (risk ratio 0.21, 95% confidence interval 0.09 to 0.47) and 5-year (risk ratio 0.31, 95% confidence interval 0.18 to 0.54) mortality rates in 1990 to 1999. Conclusions-In the present community-based sample, we observed an increase in the incidence of heart failure in recent decades that paralleled the decrease in mortality after MI.

Background: While regular exercise exposure is associated with lower risk of cardiovascular disease (CVD) and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans. Methods: Cardiopulmonary exercise testing (CPET) and metabolite profiling was performed on Framingham Heart Study (FHS) participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411). Results: We observed changes in circulating levels for 502 of 588 measured metabolites from rest to peak exercise (exercise duration 11.9±2.1 minutes) at a 5% false discovery rate (FDR). Changes included reductions in metabolites implicated in insulin resistance (glutamate -29%, P=1.5x10 -55 , dimethylguanidinovaleric acid -18%, P=5.8x10 -18 ), and increases in metabolites associated with lipolysis (1-methylnicotinamide, +33%, P=6.1x10 -67 ), nitric oxide bioavailability (arginine/ornithine + citrulline, +29%, P=2.8x10 -169 ), and adipose browning (12,13-dihydroxy-9Z-octadecenoic acid +26%, P=7.4x10 -38 ), among other pathways relevant to cardiometabolic risk. We assayed 177 metabolites in a separate FHS replication sample (n=783, age 54±8 years, 51% women) and observed concordant changes in 164 metabolites (92.6%) at 5% FDR. Exercise-induced metabolite changes were variably related to the amount of exercise performed (peak workload), sex, and body mass index (BMI). There was attenuation of favorable excursions in some metabolites in individuals with higher BMI and greater excursions in select cardioprotective metabolites in women despite less exercise performed. Distinct pre-exercise metabolite levels were associated with different physiologic dimensions of fitness (e.g., ventilatory efficiency, exercise blood pressure, peak VO 2 ). We identified four metabolite signatures of exercise response patterns that were then analyzed in a separate cohort (Framingham Offspring Study; n=2045, age 55±10 years, 51% women), two of which were associated with overall mortality over median follow-up of 23.1 years (P≤0.003 for both). Conclusions: In a large sample of community-dwelling individuals, acute exercise elicits widespread changes in the circulating metabolome. Metabolic changes identify pathways central to cardiometabolic health, CVD, and long-term outcome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise for future study.