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Falls Church, VA, United States

Koh K.K.,Gachon University | Sakuma I.,Cardiovascular Medicine | Quon M.J.,U.S. National Institutes of Health

Reciprocal relationships between endothelial dysfunction and insulin resistance suggest that therapies improving endothelial dysfunction will simultaneously improve insulin sensitivity and other metabolic parameters. However, previous studies with some statins either did not alter insulin sensitivity or promoted insulin resistance despite significant improvements in endothelial dysfunction and decreases in circulating pro-inflammatory markers. This may be due to pleiotropic or off-target effects of some statins to cause insulin resistance by diverse mechanisms unrelated to endothelial dysfunction. Indeed, there is evidence of other differential metabolic actions of distinct statins including effects on hydroxymethylglutaryl-CoA reductase inhibition, isoprotenoid synthesis, calcium release, glucose transport, insulin secretion, and/or insulin resistance. Pravastatin increases expression of adiponectin mRNA, enhances adiponectin secretion, increases plasma levels of adiponectin, and enhances insulin sensitivity in mice and humans. Clinical studies including large scale randomized controlled trials demonstrate potential differences between individual statins, with pravastatin promoting risk reduction for new onset of diabetes. Conversely, other statins including atorvastatin, rosuvastatin, and simvastatin all promote significant increase in this risk. Given the frequent concordance of metabolic diseases including diabetes, obesity, and metabolic syndrome with cardiovascular diseases associated with hyperlipidemia, it is important to understand the potential metabolic risks and benefits of therapies with distinct statins. In this review, we discuss these differential effects of statins on metabolic homeostasis and insulin sensitivity. © 2010 Elsevier Ireland Ltd. Source

Singh M.,Mayo Medical School | Holmes Jr. D.R.,Mayo Medical School | Dehmer G.J.,Scott and White Healthcare | Lennon R.J.,Mayo Medical School | And 4 more authors.
JAMA - Journal of the American Medical Association

Context: Percutaneous coronary interventions are performed at centers without onsite surgery, despite current guidelines discouraging this. Objective: To assess literature comparing rates of in-hospital mortality and emergency coronary artery bypass grafting surgery at centers with and without on-site surgery. Data Sources: A systematic search of studies published between January 1990 and May 2010 was conducted using MEDLINE, EMBASE, and Cochrane Review databases. Study Selection: English-language studies of percutaneous coronary intervention performed at centers with and without on-site surgery providing data on in-hospital mortality and emergency bypass were identified. Two study authors independently reviewed the 1029 articles originally identified and selected 40 for analysis. Data Extraction: Study title, time period, indication for angioplasty, and outcomes were extracted manually from all selected studies, and quality of each study was assessed using the strengthening the reporting of observational studies in epidemiology (STROBE) checklist. Data Synthesis: High-quality studies of percutaneous coronary interventions performed at centers with and without on-site surgery were included. Pooled-effect estimates were calculated with random-effects models. Analyses of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction of 124 074 patients demonstrated no increase in in-hospital mortality (no on-site surgery vs on-site surgery: observed risk, 4.6% vs 7.2%; odds ratio [OR], 0.96; 95% CI, 0.88-1.05; I 2 = 0%) or emergency bypass (observed risk, 0.22% vs 1.03%; OR, 0.53; 95% CI, 0.35-0.79; I 2 = 20%) at centers without on-site surgery. For nonprimary percutaneous coronary interventions (elective and urgent, n = 914 288), the rates of in-hospital mortality (observed risk, 1.4% vs 2.1%; OR, 1.15; 95% CI, 0.93-1.41; I 2 = 46%) and emergency bypass (observed risk, 0.17% vs 0.29%; OR, 1.21; 95% CI, 0.52-2.85; I 2 = 5%) were not significantly different at centers without or with on-site surgery. Conclusion: Percutaneous coronary interventions performed at centers without onsite surgery, compared with centers with on-site surgery, were not associated with a higher incidence of in-hospital mortality or emergency bypass surgery. ©2011 American Medical Association. All rights reserved. Source

Magnesium (Mg) , one of the fundamental minerals acting the co-factor of about 300 kinds of enzymes and natural Ca channel blocker, plays an important role of cardiovascular, neurological, and metabolic functions in physiological, and pathophysiological conditions. Common abnormal Mg metabolism is an absolute or relative deficiency of Mg due to an attenuated Mg intake and an enhanced urinary Mg excretion, particularly in the metabolic syndrome (MetS) , type 2 diabetes (DM) , chronic heart failure (CHF) and hemodialysis (HD) patients with diabetes. It has been reported the Mg deficiency relating to enhanced risk of MetS and type 2 DM, and to fatal cardiac events in CHF and an atherosclerotic, vascular calcification in HD patients. On the otherhand, severe and fatal hypermagnesemia is very rare, except for the condition associated with high dose administration of Mg, renal failure and an abnormally enhanced Mg absorption from damaged intestine in the mesenteric ischemia/infarction, severe constipation or ileus. In this paper, we conduct to review and discuss the pathophysiological and pathogenetical role of the abnormal Mg metabolism focused on Mg deficiency, and the protective and therapeutic significance of Mg administration in the MetS, type 2 DM, CHF and diabetic HD patients. Source

Pollak A.W.,Cardiovascular Medicine
Current Atherosclerosis Reports

Lower extremity peripheral arterial disease (PAD) is part of the ischemic continuum of atherosclerotic vascular disease and is associated with an increased risk of myocardial infarction, stroke, and cardiovascular death. Compared to men, women with PAD are more likely to have asymptomatic disease or atypical symptoms. PAD in women is associated with decreased exercise capacity, reduced quality of life, increased risk of depression, as well as a greater risk of acute cardiovascular events and cardiovascular mortality than male counterparts. Ensuring an appropriate diagnosis of women with PAD offers an opportunity to begin risk factor modification therapy, improve walking capacity and make a timely referral for revascularization if needed. It is critical to highlight the sex-based disparities in lower extremity PAD so that we may work to improve outcomes for women with PAD. © 2015, Springer Science+Business Media New York. Source

Lee H.-Y.,Seoul National University | Sakuma I.,Cardiovascular Medicine | Ihm S.-H.,Catholic University of Korea | Goh C.-W.,Inje University | And 2 more authors.
Circulation Journal

Hypercholesterolemia and hypertension are common risk factors for cardiovascular disease (CVD). Updated guidelines emphasize target reductions of overall cardiovascular risks. Experimental studies have shown reciprocal relationships between insulin resistance (IR) and endothelial dysfunction. Hypercholesterolemia and hypertension have a synergistic deleterious effect on IR and endothelial dysfunction. Unregulated renin-angiotensin system (RAS) is important in the pathogenesis of atherosclerosis and hypertension. Various strategies with different classes of antihypertensive medications to reach target goals have failed to reduce residual CVD risk further. Of interest, treating moderate cholesterol elevations with low-dose statins in hypertensive patients reduced CVD risk by 35-40% further. Therefore, statins are important in reducing CVD risk. Unfortunately, statin therapy causes IR and increases the risk of type 2 diabetes mellitus. RAS inhibitors improve both endothelial dysfunction and IR. Further, cross-talk between hypercholesterolemia and RAS exists at multiple steps of IR and endothelial dysfunction. In this regard, combined therapy with statins and RAS inhibitors demonstrates additive/synergistic effects on endothelial dysfunction and IR in addition to lowering cholesterol levels and blood pressure when compared with either monotherapy in patients. This is mediated by both distinct and interrelated mechanisms. Therefore, combined therapy with statins and RAS inhibitors may be important in developing optimal management strategies in patients with hypertension, hypercholesterolemia, diabetes, metabolic syndrome, or obesity to prevent CVD. Source

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