Steven E Reis's research while affiliated with Heart & Vascular Outcomes Research Institute and other places

Background In the US, women have similar cardiovascular death rates as men. However, less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013 and 2019. Guideline-directed statin intensity (GDSI) at index (at least moderate intensity, defined per pooled-cohort equation) and follow-up visits were compared between sexes across ASCVD risk groups, defined by the pooled-cohort equation. Cox regression hazard ratios were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results Among 282,298 patients, (mean age ∼ 50 years) 17.1 % women and 19.5 % men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-up were lower compared to high-risk men (2-years: 27.7 vs 32.0 %, and 5-years: 47.2 vs 55.2 %, p < 0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA among both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22–1.59]) vs. men (HR=1.67 [1.50–1.86]) of similar risk (p value interaction=0.004). Conclusion In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to remain on GDSI compared to high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Background Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). Objective Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. Methods We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and ‘moderate or high’ intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. Results Compared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17–1.95); p<0.01], stroke [HR 1.47 (1.14–1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19–1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. Conclusion Lack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Background Emerging data in the general population and those with coronary artery disease demonstrate higher risk of adverse outcomes with high (>70 mg/dL) HDL-C levels. There are limited data on the risk of adverse outcomes in women with suspected ischemic heart disease. Objective To investigate relationships between high (>70 mg/dL), average (50–70 mg/dL), and low (<50 mg/dL) HDL-C levels with major adverse cardiac events (MACE) (death, myocardial infarction, stroke, and heart failure hospitalization), and all-cause mortality in women referred for coronary angiography for suspected myocardial ischemia. Methods A total of 607 women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) original cohort (NCT00000554) with available HDL-C values were included in this analysis. Associations between HDL-C level and outcomes were evaluated using both multivariate Cox proportional hazard regression and spline regression analysis. Results The mean age was 59 ± 12 years, 62 % had 3 or more cardiac risk factors, and 66 (10.9 %) had a high HDL—C. High and low HDL-C were both associated with higher MACE risk compared to average HDL-C after adjusting for demographic and clinical characteristics (HR 1.80, CI 1.03–3.14, p = 0.038; HR 1.63, CI 1.09–2.42, p = 0.016, respectively). Similarly, high, and low HDL-C were associated with higher risk of all-cause mortality (HR 3.64, CI 1.84–7.20, p < 0.001; HR 2.81, CI 1.67–4.71, p < 0.001, respectively). Conclusions High and low HDL-C levels are both independently associated with higher MACE and all-cause mortality in women with suspected ischemia undergoing coronary angiography.

Introduction: Atherosclerotic cardiovascular disease (ASCVD) risk factors in mid-life have been associated with cognitive decline and late-life dementia. However, the role of these risk factors in preclinical Alzheimer's disease (AD) pathophysiology remains elusive. We investigated whether mid-life 10-year pooled cohort equations (PCE) based ASCVD risk is associated with late-life amyloid, tau, neurodegeneration [AT(N)] measures and white matter hyperintensities (WMHI). Methods: Participants enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study between 2003-2005 (mid-life) and underwent brain MRI and PET scans in 2018-2022 (age >65 years, late-life) to detect and quantify amyloid (A, PiB-PET) and tau (T, Flortaucipir (FTP) PET) deposition, cortical thickness (N) and white matter hyperintensities (WMHIs). Mid-life PCE ASCVD risk was categorized as; borderline (5%-7.4%), intermediate (7.5%- <15%), or high (≥15%). Association of midlife ASCVD risk HR (5% CI) was assessed using logistic and linear regressions with A, T, or N and chi square beta coefficients for WMHI in latelife. Results: Over a ~16y follow up, in 135 participants (mean age 73y), A and T showed no significant association with mid-life ASCVD risk. Neurodegeneration had a graded association with mid-life ASCVD risk categories (ORASCVD high vs low risk% 6.98 [2.44-19.95]; p<0.05) driven by self-identified Black race and age. In a subset n=60, ASCVD risk score was also associated with WMHIs ((β=0.42 plusmn; 0.22; p=0.05) in a model adjusted for inflammation and education. Conclusions: In this asymptomatic, diverse cohort, 10y ASCVD risk was predictive of late-life neurodegeneration and white matter hyperintensities but not amyloid or tau. These data suggest that ASCVD risk factors in midlife may lead to a state of vulnerability (through increased neurodegeneration and white matter hyperintensities) which may progress to cognitive decline and dementia. Further mechanistic studies are warranted to test this hypothesis.

Background In the US, women have similar cardiovascular death rates than men. Less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. Methods Statin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013-2019. Guideline-directed statin intensity (GDSI) at index and follow-up visits were compared among sexes across ASCVD risk groups, defined by pooled-cohort equation. Cox regression hazard ratios (HR) [95% CI] were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. Results Among 282,298 patients, (mean age ∼ 50 years) 17.1% women and 19.5% men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-ups was lower compared to high-risk men (2-years: 27.7 vs 32.0%, and 5-years: 47.2 vs 55.2%, p<0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA amongst both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22-1.59]) versus men (HR=1.67 [1.50-1.86]) of similar risk (p value interaction=0.004). Conclusion In a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to be initiated on GDSI compared with high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Background Cardiovascular (CV) disease is associated with dementia and Alzheimer’s disease (AD), but its relationship with AD pathology remains elusive. We examined whether mid‐life arterial stiffness, endothelial function, and blood pressure are associated with late‐life beta‐amyloid (Aß) and tau burden. Method Participants in the Heart Strategies Concentrating on Risk (SCORE) study completed cardiovascular phenotyping between 2003‐2005 (midlife; 45‐59 years) and up to three brain PET sessions between 2018‐2022 (late‐life; >65 years). Mid‐life assessments included augmentation index (AI75; N = 134) as a measure of arterial stiffness, Framingham reactive hyperemia index (fRHI; N = 130) as a measure of endothelial function, and systolic‐blood pressure (SBP; N = 141); late‐life measures were global [ ¹¹ C]Pittsburgh Compound‐B (PiB) standardized uptake value ratio (SUVR) and regional (medial temporal, entorhinal, inferior temporal, amygdala) [ ¹⁸ F]flortaucipir (FTP) SUVR as indices of Aß and tau deposition, respectively. In individual linear regression models, we tested associations of mid‐life AI75, RHI, and SBP with late‐life PiB and FTP SUVRs. We used mixed effects models to examine these relationships longitudinally. All models were adjusted for time between CV and PET measurements, baseline age, sex, racialization, apolipoprotein‐E4, BMI, and history of hypertension, high cholesterol, smoking, and diabetes. Result In multivariable models, higher mid‐life SBP was associated with lower late‐life FTP SUVR in the medial temporal lobe (β = ‐0.20, p = 0.04) and inferior temporal gyrus (β = ‐0.23, p = 0.01; Table 1 ); higher mid‐life SBP was also negatively associated with FTP SUVR trajectories in these regions (medial temporal lobe: β = ‐0.0004, p = 0.02; inferior temporal gyrus: β = ‐0.001, p = 0.01; Table 2 ). We did not detect significant relationships of mid‐life AI75 or RHI with late‐life FTP SUVRs (p≥0.05) or between any mid‐life cardiovascular measures and late‐life PiB SUVR (p≥0.08). Conclusion In this dementia‐free, community‐based cohort, higher mid‐life SBP was associated with lower late‐life regional tau deposition and accumulation. Though counterintuitive, our findings are consistent with results of cross‐sectional studies, which suggest that CV risk factors may be followed by an initial brain arteriole response that is protective against tau accumulation through early years of late‐adulthood 1,2 . Future studies should interrogate the potential mechanisms and age‐modifying effects that may underlie the relationship between mid‐life CV risk factors and late‐life tau deposition.