Geriatrics and the Perioperative Surgical Home.

An ever-changing health care system with a constantly increasing aging surgical population creates both opportunities for providing improved health care as well as significant challenges. Coordinated health care initiatives are needed if one is to adequately balance the need for evidence-based improved patient outcomes and the often-associated increased costs. In this article the authors postulate that a protocol-driven, multidisciplinary approach may be a pathway for implementing an effective triple aim to health care, especially in a frail geriatric population.

Effect of Bile Acid Sequestrants on the Risk of Cardiovascular Events: A Mendelian Randomization Analysis.

BACKGROUND: Statins lower low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD), but they may be ineffective or not tolerated. Bile acid sequestrants (BAS) reduce LDL-C, yet their clinical efficacy on CAD remains controversial. METHODS AND RESULTS: We conducted a systematic review and meta-analysis of randomized controlled trials to assess the effect of cholestyramine and colesevelam. We then used Mendelian randomization to estimate the effect of BAS on reducing the risk of CAD. First, we quantified the effect of rs4299376 (ABCG5/ABCG8), which affects the intestinal cholesterol absorption pathway targeted by BAS and then we used these estimates to predict the effect of BAS on CAD. Nineteen randomized controlled trials with a total of 7021 study participants were included. Cholestyramine 24 g/d was associated with a reduction in LDL-C of 23.5 mg/dL (95% confidence interval [CI] -26.8,-20.2; N=3806) and a trend toward reduced risk of CAD (odds ratio 0.81, 95% CI 0.70-1.02; P=0.07; N=3806), whereas colesevelam 3.75 g/d was associated with a reduction in LDL-C of 22.7 mg/dL (95% CI -28.3, -17.2; N=759). Based on the findings that rs4299376 was associated with a 2.75 mg/dL decrease in LDL-C and a 5% decrease in risk of CAD outcomes, we estimated that cholestyramine was associated with an odds ratio for CAD of 0.63 (95% CI 0.52-0.77; P=6.3×10(-6)) and colesevelam with an odds ratio of 0.64 (95% CI 0.52-0.79, P=4.3×10(-5)), which were not statistically different from BAS clinical trials (P>0.05). CONCLUSIONS: The cholesterol lowering effect of BAS may translate into a clinically relevant reduction in CAD.

Association between shortened leukocyte telomere length and cardiometabolic outcomes: systematic review and meta-analysis.

BACKGROUND: Telomeres are repetitive, gene-poor regions that cap the ends of DNA and help maintain chromosomal integrity. Their shortening is caused by inflammation and oxidative stress within the cellular environment and ultimately leads to cellular senescence. Shortened leukocyte telomere length is hypothesized to be a novel biomarker for age and age-related diseases, yet reports on its association with cardiometabolic outcomes in the literature are conflicting. METHODS AND RESULTS: MEDLINE (1966 to present) and EMBASE (1980 to present) were last searched on September 9, 2013. Reference lists of retrieved citations were hand searched for relevant studies. No restrictions were placed on sample size, language, or publication type or date. Fifteen cohort and 12 case-control studies reporting the association between leukocyte telomere length and stroke, myocardial infarction, and type 2 diabetes mellitus were independently selected for inclusion by 2 reviewers. Data extraction and risk of bias assessment were completed independently by 2 reviewers using predefined criteria. Studies were pooled using the generic inverse variance method and both fixed and random effects models. A 1-SD decrease in leukocyte telomere length was significantly associated with stroke (odds ratio, 1.21; 95% confidence interval, 1.06-1.37; I(2)=61%), myocardial infarction (odds ratio, 1.24; 95% confidence interval, 1.04-1.47; I(2)=68%), and type 2 diabetes mellitus (odds ratio, 1.37; 95% confidence interval, 1.10-1.72; I(2)=91%). Stratification by measurement technique, study design, study size, and ethnicity explained heterogeneity in certain cardiometabolic outcomes. CONCLUSIONS: Shortened leukocyte telomere length demonstrates a significant association with stroke, myocardial infarction, and type 2 diabetes mellitus. Larger, well-designed studies are needed to confirm these findings and explore sources of heterogeneity.

Genetic markers of inflammation and their role in cardiovascular disease.

Atherosclerosis and associated cardiovascular diseases (CVD) are multifaceted disorders, influenced by environmental and heritable risk factors. Inflammation plays a significant role in each stage of atherosclerosis and as such, discovery and characterization of inflammatory biomarkers associated with risk of CVD is an active area of research. Because of the strong predicted genetic components of both CVD and inflammatory biomarkers, there is interest in identifying genetic determinants of inflammatory markers and characterizing their role in CVD. Recent developments in the methodological approaches of genetic epidemiology, especially genome-wide association studies and Mendelian randomization studies, have been effective in identifying novel gene associations and determining the causality of these genes with CVD. In this review, we will summarize the current understanding of the genetic architecture of inflammatory markers. The markers selected for this review include C-reactive protein, soluble intercellular adhesion molecule-1, interleukin-6, and P-selectin.