Population aging, obesity, and physical inactivity are notable public health challenges. By 2030, 22% of the US population, or 70 million individuals, will be older than 65 years.¹ Approximately 32% of Americans are obese,² and the vast majority of US adults do not engage in regular physical activity.³ A high proportion of adults have levels of functional capacity that are low enough to increase mortality risk.⁴ Levels of physical activity and functional aerobic capacity each decline steadily with age,^5,6 while the prevalence of obesity tends to increase with age. Total medical expenditures associated with inactivity and obesity are greatest in the older population, a fact that underscores the significant economic burden to society posed by an aging population of inactive obese individuals.⁷

Background— Few studies have reported the relationship between cardiorespiratory fitness and metabolic syndrome incidence, particularly in women. Methods and Results— We prospectively studied 9007 men (mean±SD age, 44±9 years; body mass index, 25±3 kg/m ² ) and 1491 women (age, 44±9 years; body mass index, 22±2 kg/m ² ) who were free of metabolic syndrome and for whom measures of waist girth, resting blood pressure, fasting lipids, and glucose were taken during baseline and follow-up examinations. Baseline cardiorespiratory fitness was quantified as duration of a maximal treadmill test. Metabolic syndrome was defined with NCEP ATP-III criteria. During a mean follow-up of 5.7 years, 1346 men and 56 women developed metabolic syndrome. Age-adjusted incidence rates were significantly lower (linear trend, P <0.001) across incremental thirds of fitness in men and women. After further adjustment for potential confounders, multivariable hazard ratios for incident metabolic syndrome among men in the low, middle, and upper thirds of fitness, were 1.0 (referent), 0.74 (95% CI, 0.65 to 0.84), and 0.47 (95% CI, 0.40 to 0.54) (linear trend P <0.001); in women, they were 1.0 (referent), 0.80 (95% CI, 0.44 to 1.46), and 0.37 (95% CI, 0.18 to 0.80) (linear trend P =0.01), respectively. Similar patterns of significant inverse associations between fitness and metabolic syndrome incidence were seen when men were stratified on categories of body mass index, age, and number of baseline metabolic risk factors, but patterns were variable in women. Conclusions— Low cardiorespiratory fitness is a strong and independent predictor of incident metabolic syndrome in women and men. Clinicians should consider the potential benefits of greater cardiorespiratory fitness in the primary prevention of metabolic syndrome, particularly among patients who have already begun to cluster metabolic syndrome components.

Coronary artery calcium (CAC), a measure of subclinical coronary heart disease (CHD), may be useful in identifying asymptomatic persons at risk of CHD events. The current study included 10,746 adults who were 22–96 years of age, were free of known CHD, and had their CAC quantified by electron-beam tomography at baseline as part of a preventive medical examination at the Cooper Clinic (Dallas, Texas) during 1995–2000. During a mean follow-up of 3.5 years, 81 hard events (CHD death, nonfatal myocardial infarction) and 287 total events (hard events plus coronary revascularization) occurred. Age-adjusted rates (per 1,000 person-years) of hard events were computed according to four CAC categories: no detectable CAC and incremental sex-specific thirds of detectable CAC; these rates were, respectively, 0.4, 1.5, 4.8, and 8.7 (trend p < 0.0001) for men and 0.7, 2.3, 3.1, and 6.3 (trend p = 0.02) for women. CAC levels also were positively associated with rates of total CHD events for women and men (trend p < 0.0001 each). The association between CAC and CHD events remained significant after adjustment for CHD risk factors. CAC was associated with CHD events in persons with no baseline CHD risk factors and in younger (aged 65 years) study participants. These findings show that CAC is associated with an increased risk of CHD events in asymptomatic women and men.

Diabetes has reached epidemic proportions worldwide and is associated with a large economic burden, increased risk of cardiovascular disease, and premature mortality. Hyperglycemia is the hallmark clinical manifestation of diabetes and evolves through a multifactorial etiology of genetic, environmental, and behavioral enablers. Approximately 90% of diabetes cases are the non-insulin-dependent phenotype, which is characterized by a progressive deterioration in insulin-mediated glucose disposal, particularly by peripheral tissues. Our hypothesis is that the most proximal behavioral cause of insulin resistance is physical inactivity. Indeed, several streams of scientific research have demonstrated a role for physical activity in the etiology and prevention of diabetes and its related morbidity. In this review we will discuss some of the key observational and experimental studies that have examined associations among physical activity, cardiorespiratory fitness, and non-insulin-dependent diabetes.

To discuss assessing physical activity, cardiorespiratory fitness, and adiposity in the context of examining their prospective joint associations with mortality in cohort studies. Accurate and comprehensive assessment of free-living physical activity patterns and related energy expenditure is difficult. Cardiorespiratory fitness is a reproducible measure associated with recent physical activity patterns; however, its assessment has been considered impractical in epidemiologic studies. Likewise, objective measures of adiposity and fat distribution often are not feasible in large studies. Thus, physical activity and adiposity exposures typically are quantified using self-reports of physical activity habits and of height and weight to compute body mass index. When considered jointly, adults with higher levels of fitness or reported physical activity tend to have lower mortality risk than their unfit and inactive peers within the same body mass index group. Accumulating evidence suggests that higher physical activity or fitness attenuates the health risks of obesity. Available data largely are based on crude measures of physical activity and body habitus, which may obscure their association with disease risk. Accurate measures must be included in epidemiologic studies to improve estimation of the independent and joint associations of these exposures with health outcomes.

Background: Presence of clonal hematopoiesis of indeterminate potential (CHIP) is associated with a higher risk of atherosclerotic cardiovascular disease, cancer, and mortality. The relationship between a healthy lifestyle and CHIP is unknown. Methods and Results: This analysis included 8709 postmenopausal women (mean age, 66.5 years) enrolled in the WHI (Women's Health Initiative), free of cancer or cardiovascular disease, with deep‐coverage whole genome sequencing data available. Information on lifestyle factors (body mass index, smoking, physical activity, and diet quality) was obtained, and a healthy lifestyle score was created on the basis of healthy criteria met (0 point [least healthy] to 4 points [most healthy]). CHIP was derived on the basis of a prespecified list of leukemogenic driver mutations. The prevalence of CHIP was 8.6%. A higher healthy lifestyle score was not associated with CHIP (multivariable‐adjusted odds ratio [OR] [95% CI], 0.99 [0.80–1.23] and 1.13 [0.93–1.37]) for the upper (3 or 4 points) and middle category (2 points), respectively, versus referent (0 or 1 point). Across score components, a normal and overweight body mass index compared with obese was significantly associated with a lower odds for CHIP (OR, 0.71 [95% CI, 0.57–0.88] and 0.83 [95% CI, 0.68–1.01], respectively; P ‐trend 0.0015). Having never smoked compared with being a current smoker tended to be associated with lower odds for CHIP. Conclusions: A healthy lifestyle, based on a composite score, was not related to CHIP among postmenopausal women. However, across individual lifestyle factors, having a normal body mass index was strongly associated with a lower prevalence of CHIP. These findings support the idea that certain healthy lifestyle factors are associated with a lower frequency of CHIP.