Bradley R. Lewis

Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

Genome-wide association studies (GWAS) have revealed many single nucleotide polymorphisms (SNPs) associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017). Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI) = 0.80 (0.66, 0.95); women: OR (95%CI) = 0.83 (0.66, 1.03)). We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081), and independently in the alcohol-dependent cases (p = 0.046). Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

Cancer History Portends Worse Acute and Long-term Noncardiac (but Not Cardiac) Mortality After Primary Percutaneous Coronary Intervention for Acute ST-Segment Elevation Myocardial Infarction

OBJECTIVE To define the effect of a history of cancer on in-hospital and long-term mortality after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). PATIENTS AND METHODS In this retrospective cohort study of 2346 patients with STEMI enrolled in the Mayo Clinic PCI registry from November 1, 2000, through October 31, 2010, we identified 261 patients (11.1%) with a history of cancer. The in-hospital and long-term outcomes (median follow-up, 6.2 years; interquartile range=4.3-8.5 years), including cardiac and noncardiac death and heart failure hospitalization, of these patients were compared with those of 1313 cancer-negative patients matched on age, sex, family history of coronary artery disease, and date of STEMI. RESULTS Patients with cancer had higher in-hospital noncardiac (1.9% vs 0.4%; P=.03) but similar cardiac (5.8% vs 4.6%; P=.37) mortality as matched controls. The group at highest acute mortality risk were those diagnosed as having cancer within 6 months before STEMI (hazard ratio [HR]=7.0; 95% CI, 1.4-34.4; P=.02). At 5 years, patients with cancer had similar cardiac mortality (4.2% vs 5.8%; HR=1.27; 95% CI, 0.77-2.10; P=.35) despite more heart failure hospitalizations (15% vs 10%; HR=1.72; 95% CI, 1.18-2.50; P=.01) but faced higher noncardiac mortality (30.0% vs 11.0%; HR=3.01; 95% CI, 2.33-3.88; P<.001) than controls, attributable solely to cancer-related deaths. CONCLUSION One in 10 patients in this contemporary registry of patients undergoing primary PCI for STEMI has a history of cancer. These patients have more than a 3 times higher acute in-hospital and long-term noncardiac mortality risk but no increased acute or long-term cardiac mortality risk with guideline-recommended cardiac care.

Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls (n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls (p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls (p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle–brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

Handheld echocardiography during hospitalization for acute myocardial infarction

Handheld echocardiography (HHE) is concordant with standard transthoracic echocardiography (TTE) in a variety of settings but has not been thoroughly compared to traditional TTE in patients with acute myocardial infarction (AMI).

Low Body Mass Index, Serum Creatinine, and Cause of Death in Patients Undergoing Percutaneous Coronary Intervention

Background Low body mass index (BMI) and serum creatinine are surrogate markers of frailty and sarcopenia. Their relationship with cause‐specific mortality in elderly patients undergoing percutaneous coronary intervention is not well studied. Methods and Results We determined long‐term cardiovascular and noncardiovascular mortality in 9394 consecutive patients aged ≥65 years who underwent percutaneous coronary intervention from 2000 to 2011. BMI and serum creatinine were divided into 4 categories. During a median follow‐up of 4.2 years (interquartile range 1.8–7.3 years), 3243 patients (33.4%) died. In the multivariable model, compared with patients with normal BMI, patients with low BMI had significantly increased all‐cause mortality (hazard ratio [HR] 1.4, 95% CI 1.1–1.7), which was related to both cardiovascular causes (HR 1.4, 95% CI 1.0–1.8) and noncardiovascular causes (HR 1.4, 95% CI 1.06–1.9). Compared with normal BMI, significant reduction was noted in patients who were overweight and obese in terms of cardiovascular mortality (overweight: HR 0.77, 95% CI 0.67–0.88; obese: HR 0.80, 95% CI 0.70–0.93) and noncardiovascular mortality (overweight: HR 0.85, 95% CI 0.74–0.97; obese: HR 0.82, 95% CI 0.72–0.95). In a multivariable model, in patients with normal BMI, low creatinine (≤0.70 mg/dL) was significantly associated with increased all‐cause mortality (HR 1.8, 95% CI 1.3–2.5) and cardiovascular mortality (HR 2.3, 95% CI 1.4–3.8) compared with patients with normal creatinine (0.71–1.0 mg/dL); however, this was not observed in other BMI categories. Conclusions We identified a new subgroup of patients with low serum creatinine and normal BMI that was associated with increased all‐cause mortality and cardiovascular mortality in elderly patients undergoing percutaneous coronary intervention. Low BMI was associated with increased cardiovascular and noncardiovascular mortality. Nutritional support, resistance training, and weight‐gain strategies may have potential roles for these patients undergoing percutaneous coronary intervention.

Microvascular obstruction in non-infarct related coronary arteries is an independent predictor of major adverse cardiovascular events in patients with ST segment-elevation myocardial infarction

BACKGROUND Coronary microvascular obstruction (MVO) in infarct-related artery (IRA) territory has been associated with worse cardiovascular outcomes in patients presenting with ST-segment elevation myocardial infarction. However, the prognostic value of non-IRA MVO in this patient population remains unknown. METHODS AND RESULTS One hundred ninety nine patients presenting to our institution with STEMI were enrolled. All patients underwent primary percutaneous coronary intervention per institutional STEMI protocol followed by a cardiac MRI within 1 week of presentation and the IRA and non-IRA MVO segments were determined. All cause death, recurrent myocardial infarction, hospitalization for heart failure, and ventricular tachycardia were counted as major adverse cardiovascular events (MACE). Patients with non-IRA MVO had lower composite MACE free survival at 6 months (HR 2.15, 95% CI, 1.06-4.35; p = 0.029) compared to those without non-IRA MVO. In a sub-analysis of patients with multi vessel disease (MVD), patients with non-IRA MVO also had lower composite MACE-free survival at 6 months as compared to those without non-IRA MVO (HR 2.47, 95% CI, 1.02-5.97; p = 0.037). Non-IRA MVO continued to be predictive of MACE in a cox proportional hazards model adjusting for additional prognostic factors using inverse probability weighting (p = 0.007). Non-IRA MVO was more prevalent in patients with LAD culprit vessel STEMI rather than those with RCA or Circumflex culprit vessels (p < 0.001). CONCLUSIONS Patients presenting with STEMI and non-IRA MVO have significantly lower MACE free survival at 6 months as compared to those without non-IRA MVO.