Gregory Kotler

Risk factors for mortality in lower intestinal bleeding.

BACKGROUND & AIMS Previous studies of lower intestinal bleeding (LIB) have limited power to study mortality. We sought to identify characteristics associated with in-hospital mortality in a large cohort of patients with LIB. METHODS We used the 2002 Healthcare Cost and Utilization Project Nationwide Inpatient Sample to study a cross-sectional cohort of 227,022 hospitalized patients with discharge diagnoses indicating LIB. Predictors of mortality were identified by using multiple logistic regression. RESULTS In 2002, an estimated 8737 patients with LIB (3.9%) died while hospitalized. Independent predictors of in-hospital mortality were age (age >70 vs <50 years; odds ratio [OR], 4.91; 95% confidence interval [CI], 2.45-9.87), intestinal ischemia (OR, 3.47; 95% CI, 2.57-4.68), comorbid illness (>or=2 vs 0 comorbidities, OR, 3.00; 95% CI, 2.25-3.98), bleeding while hospitalized for a separate process (OR, 2.35; 95% CI, 1.81-3.04), coagulation defects (OR, 2.34; 95% CI, 1.50-3.65), hypovolemia (OR, 2.22; 95% CI, 1.69-2.90), transfusion of packed red blood cells (OR, 1.60; 95% CI, 1.23-2.08), and male gender (OR, 1.52; 95% CI, 1.21-1.92). Colorectal polyps (OR, 0.26; 95% CI, 0.15-0.45), and hemorrhoids (OR, 0.42; 95% CI, 0.28-0.64) were associated with a lower risk of mortality, as was diagnostic testing for LIB when added to the multivariate model (OR, 0.37; 95% CI, 0.28-0.48). Hospital characteristics were not significantly related to mortality. Predictors of mortality were similar in an analysis restricted to patients with diverticular bleeding. CONCLUSIONS The all-cause in-hospital mortality rate in LIB was low (3.9%). Advanced age, intestinal ischemia, and comorbid illness were the strongest predictors of mortality.

Usefulness of Desirable Lifestyle Factors to Attenuate the Risk of Heart Failure Among Offspring whose Parents had Myocardial Infarction before Age 55 Years

Heart failure (HF) is one of the leading causes of hospitalization and death in the United States and throughout Europe. Although a higher risk for HF with antecedent myocardial infarction (MI) has been reported in offspring whose parents had MIs before age 55 years, it is unclear whether adherence to healthful behaviors can mitigate that risk. The aim of the present study was therefore to prospectively examine if adherence to healthy weight, regular exercise, moderate alcohol consumption, and abstinence from smoking can attenuate such increased HF risk. Information on parental history of MI and lifestyle factors was collected using questionnaires. Subjects adhering to ≥3 healthy lifestyle factors were classified as having good versus poor lifestyle scores. Incident HF was assessed via yearly follow-up questionnaires and validated in a subsample. During an average follow up of 21.7 ± 6.5 years, 1,323 new HF cases (6.6%), of which 190 (14.4%) were preceded by MI, occurred. Compared to subjects with good lifestyle scores and no parental histories of premature MI, multivariate adjusted hazard ratios for incident HF with antecedent MI were 3.21 (95% confidence interval 1.74 to 5.91) for subjects with good lifestyle score and parental histories of premature MI, 1.52 (95% confidence interval 1.12 to 2.07) for those with poor lifestyle score and no parental histories of premature MI, and 4.60 (95% confidence interval 2.55 to 8.30) for those with poor lifestyle scores and parental histories of premature MI. In conclusion, our data suggest that even in subjects at higher risk for HF because of genetic predisposition, adherence to healthful lifestyle factors may attenuate such an elevated HF risk.

Effect of Baseline Nutritional Status on Long-term Multivitamin Use and Cardiovascular Disease Risk: A Secondary Analysis of the Physicians’ Health Study II Randomized Clinical Trial

Importance Long-term multivitamin use had no effect on risk of cardiovascular disease (CVD) in the Physicians’ Health Study II. Baseline nutritional status may have modified the lack of effect. Objective To investigate effect modification by various baseline dietary factors on CVD risk in the Physicians’ Health Study II. Design, Setting, and Participants The Physicians’ Health Study II was a randomized, double-blind, placebo-controlled trial testing multivitamin use (multivitamin [Centrum Silver] or placebo daily) among US male physicians. The Physicians’ Health Study II included 14 641 male physicians 50 years or older, 13 316 of whom (91.0%) completed a baseline 116-item semiquantitative food frequency questionnaire and were included in the analyses. This study examined effect modification by baseline intake of key foods, individual nutrients, dietary patterns (Alternate Healthy Eating Index and Alternate Mediterranean Diet Score), and dietary supplement use. The study began in 1997, with continued treatment and follow-up through June 1, 2011. Interventions Multivitamin or placebo daily. Main Outcomes and Measures Major cardiovascular events, including nonfatal myocardial infarction, nonfatal stroke, and CVD mortality. Secondary outcomes included myocardial infarction, total stroke, CVD mortality, and total mortality individually. Results In total, 13 316 male physicians (mean [SD] age at randomization, 64.0 [9.0] years in those receiving the active multivitamin and 64.0 [9.1] years in those receiving the placebo) were observed for a mean (SD) follow-up of 11.4 (2.3) years. There was no consistent evidence of effect modification by various foods, nutrients, dietary patterns, or baseline supplement use on the effect of multivitamin use on CVD end points. Statistically significant interaction effects were observed between multivitamin use and vitamin B6 intake on myocardial infarction, between multivitamin use and vitamin D intake on CVD mortality, and between multivitamin use and vitamin B12 intake on CVD mortality and total mortality. However, there were inconsistent patterns in hazard ratios across tertiles of each dietary factor that are likely explained by multiple testing. Conclusions and Relevance The results suggest that baseline nutritional status does not influence the effect of randomized long-term multivitamin use on major CVD events. Future studies are needed to investigate the role of baseline nutritional biomarkers on the effect of multivitamin use on CVD and other outcomes. Trial Registration clinicaltrials.gov Identifier: NCT00270647

Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL): Effects on Bone Structure and Architecture

Vitamin D supplements are often used to benefit skeletal health, although data on effects of daily high-dose vitamin D alone on bone density and structure are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, randomized, placebo-controlled trial testing effects of high-dose supplemental vitamin D3 (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (FAs; 1 g/day) for the primary prevention of cancer and cardiovascular disease. The study has a mean treatment period of 5 years among 25,874 U.S. men ≥50 years and women ≥55 years old from all 50 states. The ancillary study, VITAL: Effects on Bone Structure and Architecture, is testing effects of vitamin D3 and/or omega-3 FAs on musculoskeletal outcomes and body composition in a subcohort of 771 participants. At in-person visits at the Harvard Catalyst Clinical and Translational Science Center (CTSC), participants completed bone density/architecture, body composition, and physical performance assessments at baseline and two-year follow-up. Baseline characteristics were evenly distributed among treatment groups, suggesting that any uninvestigated confounders will be evenly distributed; sex differences were also analyzed. Future analyses of the two-year follow-up visits will elucidate whether daily high-dose, supplemental vitamin D3 and/or omega-3 FAs improve musculoskeletal outcomes, helping to advance clinical and public health recommendations. CLINICAL TRIAL REGISTRATION NUMBER NCT01747447.

Association Between Markers of Inflammation and Total Stroke by Hypertensive Status Among Women.

BACKGROUND Markers of systemic inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule 1 [sICAM-1], and fibrinogen) have been associated with a greater risk of total and ischemic stroke, in addition to elevated blood pressure. However, the role of these inflammatory markers on stroke pathophysiology by hypertension status is uncertain. METHODS Blood samples were collected and assayed for hsCRP, sICAM-1, and fibrinogen among 27,330 initially healthy women from the Womens Health Study, and women were followed up from 1992 to 2013. Prior to randomization, the baseline questionnaire collected self-reported hypertension status, cardiovascular risk factors, and lifestyle factors. New cases of total, ischemic, and hemorrhagic stroke were updated annually through questionnaires and confirmed by medical records according to the National Survey of Stroke criteria. Multivariable Cox models estimated overall associations between each inflammatory marker and stroke and separately stratified by hypertension status. RESULTS We observed 629 incident total strokes over 477,278 person-years. In adjusted analyses, extreme quartiles of hsCRP and sICAM-1 were each associated with a significantly greater risk of total stroke (hsCRP: hazard ratios [HR] = 1.77, 95% confidence interval [CI]: 1.39-2.26; sICAM-1: HR = 1.28, 95% CI: 1.00-1.63). Fibrinogen was not associated with a significantly greater stroke risk. In analyses stratified by hypertension status, elevated hsCRP was associated with a nonstatistically significant greater risk of total stroke among prehypertensive and hypertensive women. CONCLUSIONS These data indicate that hsCRP and sICAM-1 are associated with hypertension status and stroke risk among women. Further work should examine the role of inflammatory markers on ischemic stroke subtypes and clarify mechanisms.