Background: Heart failure (HF) and atrial fibrillation (AF) are growing in prevalence worldwide. Few studies have assessed to what extent stage 1 hypertension in the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) blood pressure (BP) guidelines is associated with incident HF and AF. Methods: Analyses were conducted using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2,196,437; mean age, 44.0±10.9 years; 584% men). No participants were taking antihypertensive medication or had a known history of cardiovascular disease. Each participant was categorized as having normal BP (systolic BP [SBP]<120 mm Hg and diastolic BP [DBP]<80 mm Hg; n=1,155,885); elevated BP (SBP 120-129 mm Hg and DBP<80 mm Hg; n=337,390); stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg; n=459,820); or stage 2 hypertension (SBP≥140 mm Hg or DBP≥90 mm Hg; n=243,342). Using Cox proportional hazards models, we identified associations between BP groups and HF/AF events. We also calculated the population attributable fractions (PAFs) to estimate the proportion of HF and AF events that would be preventable if participants with stage 1 and stage 2 hypertension were to have normal BP. Results: Over a mean follow-up of 1,112±854 days, 28,056 incident HF and 7,774 incident AF events occurred. After multivariable adjustment, hazard ratios for HF and AF events were 1.10 (95% Confidence interval [CI], 1.05-1.15) and 1.07 (95% CI, 0.99-1.17), respectively, for elevated BP; 1.30 (95% CI, 1.26-1.35) and 1.21 (95% CI, 1.13-1.29), respectively, for stage 1 hypertension; and 2.05 (95% CI, 1.97-2.13) and 1.52 (95% CI, 1.41-1.64), respectively, for stage 2 hypertension vs normal BP. PAFs for HF associated with stage 1 and stage 2 hypertension were 23.2% (95% CI, 20.3%-26.0%) and 51.2% (95% CI, 49.2%-53.1%), respectively. The PAFs for AF associated with stage 1 and stage 2 hypertension were 17.4% (95% CI, 11.5%-22.9%) and 34.3% (95% CI, 29.1%-39.2%), respectively. Conclusions: Both stage 1 and stage 2 hypertension were associated with a greater incidence of HF and AF in the general population. The ACC/AHA BP classification system may help identify adults at higher risk for HF and AF events.

Data on the association between body mass index (BMI) and stroke are scarce. We aimed to examine the association between BMI and incident stroke (ischemic or hemorrhagic) and to clarify the relationship between underweight, overweight, and obesity and stroke risk stratified by sex. We analyzed the JMDC Claims Database between January 2005 and April 2020 including 2,740,778 healthy individuals (Median (interquartile) age, 45 (38–53) years; 56.2% men; median (interquartile) BMI, 22.3 (20.2–24.8) kg/m²). None of the participants had a history of cardiovascular disease. Each participant was categorized as underweight (BMI <18.5 kg/m²), normal weight (BMI 18.5–24.9 kg/m²), overweight (BMI 25.0–29.9 kg/m²), or obese (BMI ≥ 30 kg/m²). We investigated the association of BMI with incidence stroke in men and women using the Cox regression model. We used restricted cubic spline (RCS) functions to identify the association of BMI as a continuous parameter with incident stroke. The incidence (95% confidence interval) of total stroke, ischemic stroke, and hemorrhagic stroke was 32.5 (32.0–32.9), 28.1 (27.6–28.5), and 5.5 (5.3–5.7) per 10,000 person-years in men, whereas 25.7 (25.1–26.2), 22.5 (22.0–23.0), and 4.0 (3.8–4.2) per 10,000 person-years in women, respectively. Multivariable Cox regression analysis showed that overweight and obesity were associated with a higher incidence of total and ischemic stroke in both men and women. Underweight, overweight, and obesity were associated with a higher hemorrhagic stroke incidence in men, but not in women. Restricted cubic spline showed that the risk of ischemic stroke increased in a BMI dose-dependent manner in both men and women, whereas there was a U-shaped relationship between BMI and the hemorrhagic stroke risk in men. In conclusion, overweight and obesity were associated with a greater incidence of stroke and ischemic stroke in both men and women. Furthermore, underweight, overweight, and obesity were associated with a higher hemorrhagic stroke risk in men. Our results would help in the risk stratification of future stroke based on BMI.

Background: There have been limited data examining the age‐dependent relationship of wide‐range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age‐related associations between modifiable risk factors and the incidence of CVD. Methods and Results: We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age category. Over a mean follow‐up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years. Conclusions: The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.

Background: There have been scarce data comparing cardiovascular outcomes between individual sodium-glucose cotransporter-2 (SGLT2) inhibitors. We aimed to compare the subsequent cardiovascular risk between individual SGLT2 inhibitors. Methods: We analyzed 25,315 patients with diabetes mellitus (DM) newly taking SGLT2 inhibitors (empagliflozin: 5302, dapagliflozin: 4681, canagliflozin: 4411, other SGLT2 inhibitors: 10,921). We compared the risks of developing heart failure (HF), myocardial infarction (MI), angina pectoris (AP), stroke, and atrial fibrillation (AF) between individual SGLT2 inhibitors. Results: Median age was 52 years, and 82.5% were men. The median fasting plasma glucose and HbA1c levels were 149 (Q1-Q3:127–182) mg/dL and 7.5 (Q1-Q3:6.9–8.6) %. During a mean follow-up of 814 ± 591 days, 855 HF, 143 MI, 815 AP, 340 stroke, and 139 AF events were recorded. Compared with empagliflozin, the risk of developing HF, MI, AP, stroke, and AF was not significantly different in dapagliflozin, canagliflozin, and other SGLT inhibitors. For developing HF, compared with empagliflozin, hazard ratios of dapagliflozin, canagliflozin, and other SGLT2 inhibitors were 1.02 (95% confidence interval [CI] 0.81–1.27), 1.08 (95% CI 0.87–1.35), and 0.88 (95% CI 0.73–1.07), respectively. Wald tests showed that there was no significant difference in the risk of developing HF, MI, AP, stroke, and AF among individual SGLT2 inhibitors. We confirmed the robustness of these results through a multitude of sensitivity analyses. Conclusion: The risks for subsequent development of HF, MI, AP, stroke, and AF were comparable between individual SGLT2 inhibitors. This is the first study comparing the wide-range cardiovascular outcomes of patients with DM treated with individual SGLT2 inhibitors using large-scale real-world data.

Background: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines lowered the threshold of blood pressure (BP) for hypertension to 130/80 mm Hg. However, the clinical significance of isolated diastolic hypertension (IDH) according to the cutoff value of the 2017 ACC/AHA guidelines was uncertain. Methods and Results: We analyzed the claims database of Japan Medical Data Center (a nationwide epidemiological database). We excluded individuals who were aged <20 years, had systolic hypertension, were taking antihypertensive medication, or had prevalent cardiovascular disease, and studied 1 746 493 individuals (mean age, 42.9±10.7 years; 961 097 men [55.0%]). The average observational period was 1107±855 days. Stage 1 IDH, defined as diastolic BP 80 to 89 mm Hg, and stage 2 IDH, defined as diastolic BP ≥90 mm Hg, were found in 230 513 (13.2%) and 16 159 (0.9%) individuals, respectively. Compared with individuals with normal diastolic BP, individuals with stage 1 and stage 2 IDH were older and more likely to be men. Prevalence of classic risk factors was higher in patients with IDH. Kaplan–Meier curves showed that stage 1 and stage 2 IDH were associated with a higher incidence of cardiovascular events, defined as myocardial infarction, angina pectoris, and stroke. Multivariable analysis showed that stage 1 (hazard ratio [HR], 1.17) and stage 2 (HR, 1.28) IDH were independently associated with a higher incidence of cardiovascular events. Subgroup analyses showed that the association of IDH with cardiovascular events was seen irrespective of age and sex. Conclusions: The analysis of a nationwide epidemiological database showed that IDH based on the cutoff value in the 2017 ACC/AHA BP guidelines was associated with an elevated risk of subsequent cardiovascular events.