Abstract Body (Do not enter title and authors here): Background: Prediabetes and diabetes are associated with increased risk for hypertension (HTN) and cardiovascular disease, especially in women. Relations of glycemic variability and other glycemic phenotypes with these diseases have not been well studied in individuals without diabetes.

Methods: Framingham Heart Study (FHS) Third Generation, New Offspring Spouse, and Omni 2 participants attending Exam 4 Year 1 (n=1291) were invited to wear a Dexcom G6 Pro continuous glucose monitor (CGM) for 10 days. We included individuals who wore CGM for ≥3 full days (n=1038). Participants were excluded if they had diabetes, took glucose-lowering medication (n=133) or did not complete a mixed meal tolerance test (MMTT, n=53), resulting in a final analytic sample of 852 participants. We performed multivariable linear and logistic regression to examine associations of glucose measures (fasting and 2h-post MMTT) and CGM-metrics with blood pressure (BP) variables and prevalent HTN (defined as stage 2 HTN or taking BP medication). We standardized all predictors to 1SD, log-transformed CGM time above range >140mg/dL (TAR140), and adjusted all regression models for age, smoking status, and body mass index (BMI), stratifying by sex.

Results: Among 852 FHS participants (56.9% women; average age 60.3 years), the average BMI was 27.9 kg/m², and 30.5% had hypertension. In multivariable regression models, TAR140, mean CGM glucose, and higher blood glucose at fasting and 2h-MMTT were associated with higher odds of HTN (OR=1.20-1.38, all p<0.05). Among those without HTN (n=583), exploratory heatmaps (Figure) provide visualization of the unadjusted correlations of CGM and blood glucose related metrics with BP measures. In multivariable regression models in men and women without HTN (n=583), fasting and 2h-MMTT blood glucose were associated with systolic BP (β=1.65-2.56, p<0.001). In women only, TAR140, mean CGM glucose, coefficient of variation (CV), mean amplitude of glycemic excursion (MAGE), and mean of daily differences (MODD) were associated with pulse pressure (β=0.97-1.31, all p<0.05) and TAR140, mean CGM glucose, and MODD were also associated with systolic BP (β=1.54-1.94, all p<0.01). These associations were not significant in men (β=-0.56-0.28, all p>0.5).

Conclusions: Among individuals without diabetes or HTN, associations of CGM metrics with BP measures were observed in women, not in men, which may reveal mechanistic differences in cardiometabolic disease progression by sex.