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Metabolic syndrome, with its attendant cardiovascular complications, is reaching epidemic proportions worldwide; hence, there is intense interest in understanding the pathogenesis of and developing therapy for these common disorders. Recent studies have suggested that metabolic syndrome may be a stress response, with an underlying abnormality in the enzyme 11β-hydroxysteroid dehydrogenase. At the cellular level, the enzyme hydroxysteroid dehydrogenase type 1 (HSD1) locally regenerates active cortisol from inactive cortisone, amplifying glucocorticoid receptor activation and promoting preadipocyte differentiation and adipocyte hypertrophy. Although initial studies in transgenic mice and humans are encouraging, more data are required to conclusively prove the hypothesis that the adipose-tissue–specific overexpression of HSD1 and the resultant increase in tissue-specific cortisol concentrations result in human obesity, insulin resistance, high blood pressure, and metabolic syndrome. Currently, selective inhibitors of HSD1 are not available for human use; however, their development is under way. The use of potent and selective HSD1 inhibitors will finally confirm or refute this hypothesis and may turn out to be an effective strategy for combating these common maladies. [Copyright &y& Elsevier]

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) decrease serum cholesterol. Dyslipidemia is believed to be associated with the development of renal dysfunction. It was postulated that statins may reduce the development of renal dysfunction. The effect of statin use on the development of renal dysfunction in 197,551 patients (Department of Veterans Affairs, Veterans Integrated Service Network 16 [VISN16] database) was examined. Of these patients, 29.5% (58,332 patients) were statin users and 70.5% (139,219 patients) were not. Development of renal dysfunction was defined as doubling of baseline creatinine or increase in serum creatinine ≥0.5 mg/dl from the first to last measurement with a minimum of 90 days in between. During 3.1 years of follow-up, 3.4% of patients developed renal dysfunction. After adjustment for demographics, diabetes mellitus, smoking, hypertension, and other medications (mainly angiotensin-converting enzyme inhibitors, calcium channel blockers, and aspirin), use of statins decreased the odds of developing renal dysfunction by 13% (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82 to 0.92, p <0.0001). The beneficial effect of statins appeared to be independent of the decrease in cholesterol. Other variables that affected the development of renal dysfunction were age (OR 1.04, 95% CI 1.03 to 1.04, p <0.0001), diabetes (OR 1.77, 95% CI 1.68 to 1.86, p <0.0001), hypertension (OR 1.11, 95% CI 1.02 to 1.2, p = 0.0153), and smoking (OR 1.12, 95% CI 1.02 to 1.24, p = 0.0244). In conclusion, statin use may retard the development of renal dysfunction. The beneficial effect of statins in preventing the development of renal dysfunction appears to be independent of their lipid-lowering effect. [Copyright &y& Elsevier]

Microalbuminuria (MA) is a well-known risk factor for coronary artery disease (CAD) in diabetics and nondiabetics. It is associated with higher cardiovascular mortality, especially in diabetics. However, there are few data linking angiographic severity of CAD to microalbuminuria. We examined coronary angiograms for extent of severe CAD (luminal narrowing ≥50%) in patients with type 2 diabetes mellitus (DM) and MA (DM+MA+, n = 101), patients with DM and without MA (DM+MA−, n = 101), patients without DM and with MA (DM−MA+, n = 64), and patients without DM and MA (DM−MA−, n = 64). We also evaluated fasting glucose levels in all patients and glycosylated hemoglobin in diabetics. Patients’ mean age in the DM+MA+, DM+MA−, DM−MA+, and DM−MA− groups was similar. Gender distribution across the 4 groups was also not significantly different. There were no significant differences in the prevalence of hypertension, hypercholesterolemia, and current smoking across the 4 groups. The presence of 2- or 3-vessel CAD showed a linear increase from group DM−MA− to group DM+MA+ (p <0.001). Diabetics with MA had higher fasting glucose and glycosylated hemoglobin levels than diabetics without MA (p <0.001). Thus, patients with MA have more severe angiographic CAD than those without MA. This relation is independent of other risk factors and is particularly evident in patients with DM. [Copyright &y& Elsevier]

Echocardiographic left ventricular (LV) hypertrophy was present in 120 of 160 patients (75%) (mean age 72 ± 8 years) with systemic hypertension, coronary artery disease, and peripheral arterial disease (PAD) and in 43 of 94 age- and gender-matched patients (46%) with systemic hypertension, coronary artery disease, and no PAD (p&#60;0.001). Echocardiographic LV hypertrophy was present in 63 of 68 patients with PAD (93%) with ankle-brachial indexes (ABIs) of &#60;0.60 and in 57 of 92 patients (62%) with ABIs of 0.60 to 0.89 (p&#60;0.001). [Copyright &y& Elsevier]

No data are available comparing the long-term outcome of sirolimus-eluting stents (SESs) versus paclitaxel-eluting stents (PESs) in patients with moderate to severe renal insufficiency. The incidence of major adverse cardiac events (MACE), including death, myocardial infarction, and target vessel revascularization, during long-term follow-up were studied in patients with a glomerular filtration rate of <60 ml/min/1.73 m2, as measured by the Modification of Diet in Renal Disease (MDRD) study equation, who also underwent percutaneous coronary intervention with drug-eluting stents. Of 428 patients studied, PESs were placed in 287 patients and SESs in 141 patients. Stepwise Cox regression analyses were performed to identify significant independent risk factors for MACE. At 47 ± 19 months of follow-up, MACE had occurred in 49 (17%) of 287 patients in the PES group (mean age 71 ± 11 years, 55% men) and in 31 (22%) of 141 patients in the SES group (mean age 71 ± 12 years, 53% men). No significant difference was found in the MACE rate between the PES and SES groups. This persisted even after controlling for stent length, lesion complexity, and other co-morbidities. Also, all-cause mortality was not significantly different between the PES and SES groups (7.1% vs 8.5%, respectively). In conclusion, during long-term follow-up of patients with moderate to severe renal insufficiency, the rates of MACE and all-cause mortality were similar in the PES and SES groups. [Copyright &y& Elsevier]

Echocardiographic left ventricular (LV) hypertrophy was present in 120 of 160 patients (75%) (mean age 72 +/- 8 years) with systemic hypertension, coronary artery disease, and peripheral arterial disease (PAD) and in 43 of 94 age- and gender-matched patients (46%) with systemic hypertension, coronary artery disease, and no PAD (p<0.001). Echocardiographic LV hypertrophy was present in 63 of 68 patients with PAD (93%) with ankle-brachial indexes (ABIs) of <0.60 and in 57 of 92 patients (62%) with ABIs of 0.60 to 0.89 (p<0.001). [ABSTRACT FROM AUTHOR]

Baseline and long-term follow-up 2-dimensional echocardiograms were obtained in 160 patients with automatic implantable cardioverter-defibrillators without indications for antibradycardia pacing, who had backup ventricular pacing at a rate of 40/minute (VVI-40) or dual-chamber rate-responsive pacing at a rate of 70/minute (DDDR-70). At 37 months of follow-up for 80 patients treated with VVI-40 and 23 months of follow-up for 80 patients treated with DDDR-70, the mean left ventricular ejection fraction was 36 +/- 8% at baseline and 36 +/- 8% at follow-up and 36 +/- 7% at baseline and 30 +/- 7% at follow-up (p <0.01), respectively. At follow-up, the left ventricular ejection fraction was decreased >7% in 25 of 80 patients (31%)treated with DDDR-70 and in 9 of 80 patients (11%) treated with VVI-40 (p <0.01). A new left ventricular wall motion abnormality developed in 23 of 80 patients (29%) treated with DDDR-70 and in 11 of 80 patients (14%) treated with VVI-40 (p <0.025). [ABSTRACT FROM AUTHOR]

Baseline and long-term follow-up 2-dimensional echocardiograms were obtained in 160 patients with automatic implantable cardioverter-defibrillators without indications for antibradycardia pacing, who had backup ventricular pacing at a rate of 40/minute (VVI-40) or dual-chamber rate-responsive pacing at a rate of 70/minute (DDDR-70). At 37 months of follow-up for 80 patients treated with VVI-40 and 23 months of follow-up for 80 patients treated with DDDR-70, the mean left ventricular ejection fraction was 36 ± 8% at baseline and 36 ± 8% at follow-up and 36 ± 7% at baseline and 30 ± 7% at follow-up (p &#60;0.01), respectively. At follow-up, the left ventricular ejection fraction was decreased >7% in 25 of 80 patients (31%)treated with DDDR-70 and in 9 of 80 patients (11%) treated with VVI-40 (p &#60;0.01). A new left ventricular wall motion abnormality developed in 23 of 80 patients (29%) treated with DDDR-70 and in 11 of 80 patients (14%) treated with VVI-40 (p &#60;0.025). [Copyright &y& Elsevier]

Twenty-one of 64 patients (33%) with pulmonary embolisms with right ventricular (RV) dilation and 6 of 126 patients (5%) with pulmonary embolisms without RV dilation died during hospitalization (p &#60;0.001). In the 64 patients with RV dilation, in-hospital mortality occurred in 2 of 18 hemodynamically unstable patients (11%) who underwent pulmonary embolectomy, in 2 of 6 hemodynamically stable patients (33%) treated with thrombolytic therapy plus intravenous heparin, and in 17 of 40 hemodynamically stable patients (43%) treated with intravenous heparin (p &#60;0.025 comparing pulmonary embolectomy with no pulmonary embolectomy). [Copyright &y& Elsevier]