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Objective To determine whether vascular risk factor burden in mid‐ or late‐life associates with postmortem vascular and neurodegenerative pathologies in a community‐based sample. Methods We studied participants from the Framingham Heart Study who participated in our voluntary brain bank program. Overall vascular risk factor burden was calculated using the Framingham Stroke Risk Profile (FSRP). Mid‐life FSRP was measured at 50 to 60 years of age. Following death, brains were autopsied and semi‐quantitatively assessed by board‐certified neuropathologists for cerebrovascular outcomes (cortical infarcts, subcortical infarcts, atherosclerosis, arteriosclerosis) and Alzheimer’s disease pathology (Braak stage, cerebral amyloid angiopathy, and neuritic plaque score). We estimated adjusted odds ratios between vascular risk burden (at mid‐life and before death) and neuropathological outcomes using logistic and proportional‐odds logistic models. Results The median time interval between FSRP and death was 33.4 years for mid‐life FSRP and 4.4 years for final FSRP measurement before death. Higher mid‐life vascular risk burden was associated with increased odds of all cerebrovascular pathology, even with adjustment for vascular risk burden before death. Late‐life vascular risk burden was associated with increased odds of cortical infarcts (OR [95% CI]: 1.04 [1.00, 1.08]) and arteriosclerosis stage (OR [95% CI]: 1.03 [1.00, 1.05]). Mid‐life vascular risk burden was not associated with Alzheimer’s disease pathology, though late‐life vascular risk burden was associated with increased odds of higher Braak stage (OR [95% CI]: 1.03 [1.01, 1.05]). Interpretation Mid‐life vascular risk burden was predictive of cerebrovascular but not Alzheimer’s disease neuropathology, even after adjustment for vascular risk factors before death.

People with HIV (PWH) experience increased systemic inflammation and monocyte activation, leading to increased risk of cardiovascular events (death, stroke, and myocardial infarction) and higher coronary artery calcium scores (CACs). Vitamins D and K2 have significant anti-inflammatory effects; in addition, vitamin K2 is involved in preventing vascular calcifications in the general population. The roles of vitamins D and K in increased coronary calcifications in successfully treated PWH is less understood.We prospectively recruited 237 PWH on antiretroviral treatment (ART) and 67 healthy controls. CACs were derived from noncontrast chest computed tomography (CT) and levels of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K-dependent dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP, marker of vitamin K deficiency) were measured in plasma during a fasting state. The relationship between inflammation markers, dp-uc MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted models included 25(OH)D, MGP, sex, race, age, and markers of inflammation or monocyte activation.Overall, controls had lower median age (45.8 vs. 48.8; P = 0.03), a larger proportion of female individuals (55.2 vs. 23.6%; P 0.0001), and nonwhite (33.8 vs. 70%; P 0.0001). Among PWH, less than 1% had detectable viral load and the median CD4+ cell count was 682 (IQR: 473.00-899.00). 62.17% of the participants had zero CACs and 51.32% were vitamin D-deficient (20 ng/ml). There was no difference in detectable CACs (P = 0.19) or dp-uc MGP (P = 0.42) between PWH and controls. In adjusted models, PWH with nonzero CACs have three times greater expected CAC burden compared with controls. Every 1% increase in MGP (worse K status) decreases the probability of having CACs equal to zero by 21.33% (P = 0.01). Evidence suggests that the effects of 25(OH)D and MGP are inflammation-mediated, specifically through sVCAM, TNF-αRI, and TNF-αRII.Vitamin K deficiency is a modifiable preventive factor against coronary calcification in PWH. Further research should determine whether vitamin K supplementation would reduce systemic inflammation, vascular calcification, and risk of cardiovascular events in PWH.

Fungal endocarditis is a relatively rare occurrence with high morbidity and mortality. Patients may have an indolent and non-specific course requiring a high index of suspicion to make a diagnosis. Here, we present the case of a 33-year-old patient who presented with fevers and acute lower limb ischemia requiring a 4-compartment fasciotomy caused by septic emboli from Candida albicans endocarditis. The patient had a large vegetation in the ascending aorta associated with a mycotic aneurysm, which is an exceedingly rare location for a vegetation. We also review the literature and summarize the typical echocardiographic appearance and vegetation locations in fungal endocarditis.

Background Exercise stress tests are conventionally performed to assess risk of coronary artery disease. Using the FHS (Framingham Heart Study) Offspring cohort, we related blood pressure (BP) and heart rate responses during and after submaximal exercise to the incidence of heart failure (HF). Methods and Results We evaluated Framingham Offspring Study participants (n=2066; mean age, 58 years; 53% women) who completed 2 stages of an exercise test (Bruce protocol) at their seventh examination (1998–2002). We measured pulse pressure, systolic BP, diastolic BP, and heart rate responses during stage 2 exercise (2.5 mph at 12% grade). We calculated the changes in systolic BP, diastolic BP, and heart rate from stage 2 to recovery 3 minutes after exercise. We used Cox proportional hazards regression to relate each standardized exercise variable (during stage 2, and at 3 minutes of recovery) individually to HF incidence, adjusting for standard risk factors. On follow‐up (median, 16.8 years), 85 participants developed new‐onset HF. Higher exercise diastolic BP was associated with higher HF with reduced ejection fraction (ejection fraction Conclusions Accentuated diastolic BP during exercise with slower systolic BP and heart rate recovery after exercise are markers of HF with reduced ejection fraction risk.

Background HIV-infected individuals are at higher risk for developing cardiovascular disease (CVD). We aimed to develop a model to predict 10-year cardiovascular (CV) risk given that commonly used CVD risk assessment tools might not be accurate for HIV-infected patients. Methods We conducted a retrospective cohort study of HIV-infected patients seen at Boston Medical Center between March 2012 and January 2017. Exclusion criteria are shown in Figure 1. Patients were divided into model development and validation cohorts. Logistic regression was used to create a risk model for CV events using data from the development cohort. The relationship between risk factors and CVD risk was summarized using a point-based risk-scoring system. Areas under the receiver-operating-characteristics curve (AUC) were used to evaluate model discrimination. The model was subsequently tested using the validation cohort. Results Of 3,867 eligible HIV-infected patients, 1,914 individuals met inclusion criteria (Figure 1). There were 256 CV events in the development cohort. Ten independent prognostic factors were incorporated into the prediction function (Pmodel < 0.001). The model had excellent discrimination for CVD risk [AUC 0.94; (95% CI:0.93–0.96)] (Figure 2) and included the following variables: male sex (P < 0.001), African-American ethnicity (P = 0.023), current age (P = 0.020), age at HIV diagnosis (P = 0.006), peak HIV viral load (P = 0.012), nadir CD4 lymphocyte count (P < 0.001), hypertension (P < 0.001), hyperlipidemia (P = 0.001), diabetes (P < 0.001), and chronic kidney disease (P < 0.001). Scoring system and score sheets of risk estimates were developed to predict CV events in a 10-year follow-up period (Figures 3 and 4). The 10-parameter multiple logistic regression model also had excellent discrimination [AUC 0.96; (95% CI: 0.89–0.99)] when applied to the validation cohort. Conclusion We developed and validated a risk-scoring system based on 10 clinical factors that accurately predict the 10-year risk for CV events in an HIV-infected population. This assessment tool may provide clinicians with a rapid assessment of cardiovascular disease risk among HIV-infected patients and inform prevention measures during the era of effective antiretroviral therapy. Disclosures All Authors: No reported Disclosures.

Exercise stress testing is routinely performed to assess risk of obstructive coronary artery disease. Stress test protocols require that blood pressure and heart rate be measured at specified time points before, during, and after exercise. We examined the relations of blood pressure and heart rate

Background Adipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity‐associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community‐based sample. Methods and Results We evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid–binding protein 4, retinol‐binding protein 4, fetuin‐A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e′. In multivariable‐adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid–binding protein 4 concentrations but positively related to retinol‐binding protein 4 and leptin receptor levels ( P ≤0.002 for all). Left atrial end‐systolic dimension was inversely related to leptin but positively related to retinol‐binding protein 4 concentrations ( P ≤0.0001). E/e′ was inversely related to leptin receptor levels ( P =0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid–binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P Conclusions In our cross‐sectional study of a large, young to middle‐aged, relatively healthy community‐based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of prohypertrophic and antihypertrophic adipokines in a context‐specific manner. These observations may offer insights into the pathogenesis of the cardiomyopathy of obesity.