Abstract
The associations of estimated cardiorespiratory fitness (eCRF) during midlife with subclinical atherosclerosis, arterial stiffness, incident cardiometabolic disease, and mortality are not well understood. To examine associations of midlife eCRF with subclinical atherosclerosis, arterial stiffness, incident cardiometabolic disease, and mortality. This cohort study included 2962 participants in the Framingham Study Second Generation (conducted between 1979 and 2001). Data were analyzed from January 2020 to June 2020. eCRF was calculated using sex-specific algorithms (including age, body mass index, waist circumference, physical activity, resting heart rate, and smoking) and was categorized as: (1) tertiles of standardized eCRF at examination cycle 7 (1998 to 2001); (2) tertiles of standardized average eCRF between examination cycles 2 and 7 (1979 to 2001); and (3) eCRF trajectories between examination cycles 2 and 7, with the lowest tertile or trajectory (ie, low eCRF) as referent group. Subclinical atherosclerosis (carotid intima-media thickness [CIMT], coronary artery calcium [CAC] score); arterial stiffness (carotid-femoral pulse wave velocity [-1000/CFPWV]); incident hypertension, diabetes, chronic kidney disease (CKD), cardiovascular disease (CVD), and mortality after examination cycle 7. A total of 2962 participants were included in this cohort study (mean [SD] age, 61.5 [9.2] years; 1562 [52.7%] women). The number of events or participants at risk after examination cycle 7 (at a mean follow-up of 15 years) was 728 of 1506 for hypertension, 214 of 2268 for diabetes, 439 of 2343 for CKD, 500 of 2608 for CVD, and 770 of 2962 for mortality. Compared with the low eCRF reference value, high single examination eCRF was associated with lower CFPWV (β [SE], -11.13 [1.33] ms/m) and CIMT (β [SE], -0.12 [0.05] mm), and lower risk of hypertension (hazard ratio [HR], 0.63; 95% CI, 0.46-0.85), diabetes (HR, 0.38; 95% CI, 0.23-0.62), and CVD (HR, 0.71; 95% CI, 0.53-0.95), although it was not associated with CKD or mortality. Similarly, compared with the low eCRF reference, high eCRF trajectories and mean eCRF were associated with lower CFPWV (β [SE], -11.85 [1.89] ms/m and -10.36 [1.54] ms/m), CIMT (β [SE], -0.19 [0.06] mm and -0.15 [0.05] mm), CAC scores (β [SE], -0.67 [0.25] AU and -0.63 [0.20] AU), and lower risk of hypertension (HR, 0.54; 95% CI, 0.34-0.87 and HR, 0.48; 95% CI, 0.34-0.68), diabetes (HR, 0.27; 95% CI, 0.15-0.48 and HR, 0.31; 95% CI, 0.18-0.54), CKD (HR, 0.63; 95% CI, 0.40-0.97 and HR, 0.64; 95% CI, 0.44-0.94), and CVD (HR, 0.46; 95% CI, 0.31-0.68 and HR, 0.43; 95% CI, 0.30-0.60). Compared with the reference value, a high eCRF trajectory was associated with lower risk of mortality (HR, 0.69; 95% CI, 0.50-0.95). In this cohort study, higher midlife eCRF was associated with lower burdens of subclinical atherosclerosis and vascular stiffness, and with a lower risk of hypertension, diabetes, chronic kidney disease, cardiovascular disease, and mortality. These findings suggest that midlife eCRF may serve as a prognostic marker for subclinical atherosclerosis, arterial stiffness, cardiometabolic health, and mortality in later life.
Highlights
Compared with the low estimated cardiorespiratory fitness (eCRF) reference value, high single examination eCRF was associated with lower carotid-femoral pulse wave velocity (CFPWV) (β [SE], −11.13 [1.33] ms/m) and carotid intima-media thickness (CIMT) (β [SE], −0.12 [0.05] mm), and lower risk of hypertension, diabetes (HR, 0.38; 95% CI, 0.23-0.62), and cardiovascular disease (CVD) (HR, 0.71; 95% CI, 0.53-0.95), it was not associated with chronic kidney disease (CKD) or mortality
Downloaded From: https://jamanetwork.com/ on 11/08/2021. In this cohort study, higher midlife eCRF was associated with lower burdens of subclinical atherosclerosis and vascular stiffness, and with a lower risk of hypertension, diabetes, chronic kidney disease, cardiovascular disease, and mortality. These findings suggest that midlife eCRF may serve as a prognostic marker for subclinical atherosclerosis, arterial stiffness, cardiometabolic health, and mortality in later life
Participants with low eCRF were older and had a greater burden of subclinical atherosclerosis and arterial stiffness. (Trajectories of midlife eCRF are shown in eFigure, and a comparison of characteristics between participants who were included and excluded from analysis are available in eTable 1 in the Supplement.) Overall, participants excluded from the analysis were older and had a higher burden of cardiometabolic disease
Summary
Cardiorespiratory fitness (CRF) is inversely associated with risk of cardiovascular disease (CVD) and all-cause mortality incrementally over established CVD risk factors.[1,2,3,4,5,6] the use of CRF improves CVD and mortality risk predictions when used in conjunction with established risk factors.[7,8] Recent scientific statements from the American Heart Association emphasize the importance of assessing CRF in clinical practice.[9]. CRF is measured via cardiopulmonary exercise testing; this method requires in-person assessment with specialized equipment and trained personnel, rendering it expensive and less accessible.[9] Due to such limitations, nonexercise estimated CRF (eCRF) algorithms have been developed using readily available clinical information, such as age, sex, waist circumference, resting heart rate, and physical activity. Studies have demonstrated that the prognostic ability of eCRF for CVD risk and mortality is comparable to the use of traditional CRF testing.[10,11] little is known about the associations of eCRF during midlife with the prevalence of subclinical atherosclerosis and arterial stiffness, and with the development of cardiometabolic diseases and mortality later in life
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