Prevalence, Predictors, Progression, and Prognosis of Hypertension Subtypes in the Framingham Heart Study.

Background The epidemiology of hypertension subtypes has not been well characterized in the recent era. Methods and Results We delineated the prevalence, predictors, progression, and prognostic significance of hypertension subtypes in 8198 Framingham Heart Study participants (mean age, 46.5 years; 54% women). The prevalence of hypertension subtypes was as follows: nonhypertensive (systolic blood pressure [SBP] <140 mm Hg and diastolic blood pressure [DBP] <90 mm Hg), 79%; isolated systolic hypertension (ISH; SBP ≥140 mm Hg and DBP <90 mm Hg), 8%; isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg), 4%; and systolic-diastolic hypertension (SDH; SBP ≥140 mm Hg and DBP ≥90 mm Hg), 9%. The prevalence of ISH and SDH increased with age. Analysis of a subsample of nonhypertensive participants demonstrated that increasing age, female sex, higher heart rate, left ventricular mass, and greater left ventricular concentricity were predictors of incident ISH and SDH. Higher baseline DBP was associated with the risk of developing isolated diastolic hypertension and SDH, whereas higher SBP was associated with all 3 hypertension subtypes. On follow-up (median, 5.5 years), isolated diastolic hypertension often reverted to nonhypertensive BP (in 42% of participants) and ISH progressed to SDH (in 26% of participants), whereas SDH frequently transitioned to ISH (in 20% of participants). During follow-up (median, 14.6 years), 889 participants developed cardiovascular disease. Compared with the nonhypertensive group (referent), ISH (adjusted hazard ratio [HR], 1.57; 95% CI, 1.30-1.90) and SDH (HR, 1.66; 95% CI, 1.36-2.01) were associated with increased cardiovascular disease risk, whereas isolated diastolic hypertension was not (HR, 1.03; 95% CI, 0.68-1.57). Conclusions Hypertension subtypes vary in prevalence with age, are dynamic during short-term follow-up, and exhibit distinctive prognoses, underscoring the importance of blood pressure subphenotyping.

Association of Estimated Cardiorespiratory Fitness in Midlife With Cardiometabolic Outcomes and Mortality.

Importance: The associations of estimated cardiorespiratory fitness (eCRF) during midlife with subclinical atherosclerosis, arterial stiffness, incident cardiometabolic disease, and mortality are not well understood. Objective: To examine associations of midlife eCRF with subclinical atherosclerosis, arterial stiffness, incident cardiometabolic disease, and mortality. Design, Setting, and Participants: 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. Exposures: 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. Main Outcomes and Measures: 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. Results: 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 (ß [SE], -11.13 [1.33] ms/m) and CIMT (ß [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 (ß [SE], -11.85 [1.89] ms/m and -10.36 [1.54] ms/m), CIMT (ß [SE], -0.19 [0.06] mm and -0.15 [0.05] mm), CAC scores (ß [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). Conclusions and Relevance: 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.

Association of Mildly Reduced Kidney Function With Cardiovascular Disease: The Framingham Heart Study.

Background Data are limited on the association of mildly reduced estimated glomerular filtration rate (eGFR 60-89 mL/min per 1.73 m2) with cardiovascular disease (CVD) in the community. Methods and Results We evaluated 3066 Framingham Offspring Study participants (55% women, mean age 58 years), without clinical CVD. Using multivariable regression, we related categories of mildly reduced eGFR (80-89, 70-79, or 60-69 versus ≥90 mL/min per 1.73 m2 [referent]) to prevalent coronary artery calcium, carotid intima media thickness, and left ventricular hypertrophy, and to circulating concentrations of cardiac stress biomarkers. We related eGFR categories to CVD incidence and to progression to ≥Stage 3 chronic kidney disease (eGFR <60 mL/min per 1.73 m2) using Cox regression. Individuals with eGFR 60-69 mL/min per 1.73 m2 (n=320) had higher coronary artery calcium score (odds ratio 1.69; 95% CI 1.02-2.80) compared with the referent group. Individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 had higher blood growth differentiating factor-15 concentrations (ß=0.131 and 0.058 per unit-increase in log-biomarker, respectively). Participants with eGFR 60-69 and 80-89 mL/min per 1.73 m2 had higher blood B-type natriuretic peptide concentrations (ß=0.119 and 0.116, respectively). On follow-up (median 16 years; 691 incident CVD and 252 chronic kidney disease events), individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 experienced higher CVD incidence (hazard ratio [HR], 1.40; 95% CI, 1.02-1.93 and 1.45, 95% CI, 1.05-2.00, respectively, versus referent). Participants with eGFR 60-69 mL/min per 1.73 m2 experienced higher chronic kidney disease incidence (HR, 2.94; 95% CI, 1.80-4.78 versus referent). Conclusions Individuals with mildly reduced eGFR 60-69 mL/min per 1.73 m2 have a higher burden of subclinical atherosclerosis cross-sectionally, and a greater risk of CVD and chronic kidney disease progression prospectively. Additional studies are warranted to confirm our findings.