Background: The associations of time‐averaged cumulative blood pressure (BP) from midlife to late life with microvasculature expressed as retinal vessel diameters is not well studied. The aim of this study was to evaluate the association of cumulative systolic BP and diastolic BP (DBP) with retinal vessel calibers, focusing on race differences. Methods and Results: The analysis included 1818 adults from the ARIC (Atherosclerosis Risk in Communities) study attending the fifth visit (2011–2013; age 77±5 years, 17.1% Black participants). Time‐averaged cumulative BPs were calculated as the sum of averaged BPs from adjacent consecutive visits (visits 1–5) indexed to total observation time (24±1 years). Summarized estimates for central retinal arteriolar equivalent and central retinal venular equivalent at the fifth visit represent average retinal vessel diameters. The arteriole:venule ratio was calculated. We tested for effect modification by race. Results from multiple linear regression models suggested that higher time‐averaged cumulative DBP (β [95% CI] per 1‐SD increase: −1.78 [−2.53, −1.02], P <0.001 and −0.005 [−0.009, −0.002], P =0.004, respectively) but not systolic BP (−0.52 [−1.30, 0.26], P =0.189 and 0.001 [−0.002, 0.005], P =0.485, respectively) was associated with smaller central retinal arteriolar equivalent and arteriole:venule ratio. The association between time‐averaged cumulative DBP and arteriole:venule ratio was strongest in White participants (interaction P =0.007). The association of cumulative systolic BP and DBP with central retinal venular equivalent was strongest in Black participants (interaction P =0.015 and 0.011, respectively). Conclusions: Exposure to higher BP levels, particularly DBP, from midlife to late life is associated with narrower retinal vessel diameters in late life. Furthermore, race moderated the association of cumulative BP exposure with retinal microvasculature.

Background: Cardiovascular autonomic neuropathy (CAN) is a severe complication of type 2 diabetes. Significant sex‐related differences have been observed in type 2 diabetes consequences such as mortality. However, the effect of sex on the association between CAN and mortality in patients with type 2 diabetes is currently unknown. Methods and Results: We assessed 7866 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, including 4730 men and 3136 women. CAN was diagnosed using a combination of heart rate variability and QT interval index, which has 3 different definitions. There were 1364 cases of all‐cause mortality and 452 cases of cardiovascular disease mortality during a median follow‐up of 9.7 years. We used multivariable Cox regression models to assess the association between different CAN definitions and mortality. In women, various CAN measures were statistically significant associated with an increased risk of all‐cause mortality (CAN1: hazard ratio [HR], 1.64 [95% CI, 1.28–2.09]; CAN2: HR, 1.58 [95% CI, 1.17–2.15]; CAN3: HR, 1.78 [95% CI, 1.20–2.65]) and mortality (CAN1: HR, 2.25 [95% CI, 1.44–3.52]; CAN 2: HR, 2.22 [95% CI, 1.28–3.87]; CAN3: HR, 3.31 [95% CI, 1.67–6.57]). CAN was not significantly associated with mortality in men. A significant multiplicative interaction of CAN and sex was observed on both mortality outcomes ( P <0.01). Conclusions: Significant sex‐related differences were observed in CAN and its associated mortality. In terms of mortality risk prevention, CAN should be given greater consideration in women with type 2 diabetes.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.

Background: Hyperglycemia is one of the proposed risk factors for cardiac autonomic neuropathy (CAN). CAN is associated with increased cardiovascular and mortality risk. But it remains unclear whether cardiovascular and mortality risk associated with CAN is mitigated by intensive glycemic treatment. Methods and Results: This secondary analysis included 7866 patients from the ACCORDION (Action to Control Cardiovascular Risk in Diabetes Follow‐On) study. CAN was defined using ECG‐derived measures. End points included primary outcome (composite of cardiovascular events) and total deaths. During a median follow‐up of 8.9 years, a total of 1341 cardiovascular events and 1364 all‐cause deaths were ascertained. Compared with standard treatment, intensive treatment reduced risk of primary outcome and total deaths among patients with CAN but not among those without CAN. Compared with absence of CAN, the presence of CAN was associated with increased risk of primary outcome and total deaths in the standard group but not in the intensive group. Significant interactions were found between CAN status and treatment arms on risk of primary outcome and total deaths. Incidence rates per 100 person‐years of primary outcome and total deaths were similar between patients without CAN and those with CAN undergoing intensive treatment. Conclusions: Intensive glycemic treatment mitigates cardiovascular and mortality risk associated with CAN and may serve as an effective way in the management of CAN.