Bailey, Kent R.

Key PointsApproximately 500 000 US VTE events occur annually; approximately one-half are related to current or recent hospitalization. VTE attack rates (2005-2010) did not change despite near-universal in-hospital VTE prophylaxis, possibly due to short prophylaxis duration.

Background: Cardiomyocytes are resistant to radiation. However, cardiac radiation exposure causes coronary microvascular endothelial inflammation, a perturbation implicated in the pathogenesis of heart failure (HF) and particularly HF with preserved ejection fraction (HFpEF). Radiotherapy for breast cancer results in variable cardiac radiation exposure and may increase the risk of HF. Methods: We conducted a population-based case-control study of incident HF in 170 female residents of Olmsted County, Minnesota (59 cases and 111 controls), who underwent contemporary (1998–2013) radiotherapy for breast cancer with computed tomography–assisted radiotherapy planning. Controls were matched to cases for age, tumor side, chemotherapy use, diabetes mellitus, and hypertension. Mean cardiac radiation dose (MCRD) in each patient was calculated from the patient’s computed tomography images and radiotherapy plan. Results: Mean age at radiotherapy was 69±9 years. Of HF cases, 38 (64%) had EF≥50% (HFpEF), 18 (31%) had EF<50% (HF with reduced EF), and 3 (5%) did not have EF measured. The EF was ≥40% in 50 of the 56 HF cases (89%) with an EF measurement. The mean interval from radiotherapy to HF was 5.8±3.4 years. The odds of HF was higher in patients with a history of ischemic heart disease or atrial fibrillation. The MCRD was 2.5 Gy (range, 0.2–13.1 Gy) and higher in cases (3.3±2.7 Gy) than controls (2.1±2.0 Gy; P =0.004). The odds ratio (95% confidence interval) for HF per log MCRD was 9.1 (3.4–24.4) for any HF, 16.9 (3.9–73.7) for HFpEF, and 3.17 (0.8–13.0) for HF with reduced EF. The increased odds of any HF or HFpEF with increasing MCRD remained significant after adjustment for HF risk factors and in sensitivity analyses matching by cancer stage rather than tumor side. Only 18.6% of patients experienced new or recurrent ischemic events between radiotherapy and the onset of HF. Conclusions: The relative risk of HFpEF increases with increasing cardiac radiation exposure during contemporary conformal breast cancer radiotherapy. These data emphasize the importance of radiotherapy techniques that limit MCRD during breast cancer treatment. Moreover, these data provide further support for the importance of coronary microvascular compromise in the pathophysiology of HFpEF.

Background: Prophylactic exclusion of the left atrial appendage (LAA) is often performed during cardiac surgery ostensibly to reduce the risk of stroke. However, the clinical impact of LAA closure in humans remains inconclusive. Methods: Of 10 633 adults who underwent coronary artery bypass grafting and valve surgery between January 2000 and December 2005, 9792 patients with complete baseline characteristics, surgery procedure, and follow-up data were included in this analysis. A propensity score–matching analysis based on 28 pretreatment covariates was performed and 461 matching pairs were derived and analyzed to estimate the association of LAA closure with early postoperative atrial fibrillation (POAF) (atrial fibrillation ≤30 days of surgery), ischemic stroke, and mortality. Results: In the propensity-matched cohort, the overall incidence of POAF was 53.9%. In this group, the rate of early POAF among the patients who underwent LAA closure was 68.6% versus 31.9% for those who did not undergo the procedure ( P <0.001). LAA closure was independently associated with an increased risk of early POAF (adjusted odds ratio, 3.88; 95% confidence interval, 2.89–5.20), but did not significantly influence the risk of stroke (adjusted hazard ratio, 1.07; 95% confidence interval, 0.72–1.58) or mortality (adjusted hazard ratio, 0.92; 95% confidence interval, 0.75–1.13). Conclusions: After adjustment for treatment allocation bias, LAA closure during routine cardiac surgery was significantly associated with an increased risk of early POAF, but it did not influence the risk of stroke or mortality. It remains uncertain whether prophylactic exclusion of the LAA is warranted for stroke prevention during non–atrial fibrillation-related cardiac surgery.

Background— Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results— Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ( + GRS). Participants in the + GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or + GRS (n=103). At the end of the study period, the + GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the + GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions— Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01936675.

Background We recently reported that normal aldosterone levels are associated with cardiovascular, renal, and metabolic disease in a sample of the US general community (Visit 1). For the current analyses we used the same cohort in a new 4‐year follow‐up study (Visit 2). Methods and Results We measured aldosterone at Visit 1 and analyzed its predictive role for new diseases at Visit 2 (n=1140). We measured aldosterone at Visit 2 and investigated its associations with disease at Visit 2 (n=1368). We analyzed aldosterone continuously and we also dichotomized the variable as whether subjects were in the third tertile versus second and first tertiles. As continuous variable at Visit 1, aldosterone predicted new onset hypertension ( HTN ) ( OR =1.36, CI =1.13–1.63, P =0.001), central obesity ( OR =1.36, CI =1.07–1.73, P =0.011), and use of lipid‐lowering drugs ( OR =1.25, CI =1.05–1.48, P =0.012) at Visit 2, after adjustment for age, sex, and body mass index. When in the third tertile (8.5–88.6 ng/dL), aldosterone predicted type 2 diabetes (T2 DM , OR =1.96, CI =1.03–3.70, P =0.039). At Visit 2, aldosterone remained associated with HTN , obesity, and chronic kidney disease ( CKD ), as reported for Visit 1. However, aldosterone was not associated with heart failure ( HF ) at Visit 1 and 2, nor was aldosterone a predictor of HF between visits. Conclusions Aldosterone predicts new HTN , central obesity, T2 DM , and use of lipid‐lowering drugs in the general community and remains associated with HTN , obesity, and CKD over 4 years. Aldosterone is not associated nor predicts HF . Further studies are warranted to evaluate aldosterone as therapeutic target in the general community.