Major adverse cardiac events in patients with moderate to severe renal insufficiency treated with first-generation drug-eluting stents.

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 m(2), 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 + or - 19 months of follow-up, MACE had occurred in 49 (17%) of 287 patients in the PES group (mean age 71 + or - 11 years, 55% men) and in 31 (22%) of 141 patients in the SES group (mean age 71 + or - 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.

Major adverse cardiac events at long-term follow-up in patients treated with single versus multiple stents during single-vessel percutaneous coronary intervention.

BACKGROUND: Although insertion of multiple stents into a single coronary vessel during single-vessel percutaneous coronary intervention (PCI) is common, there are no data on long-term occurrence of major adverse cardiac events (MACE) in patients treated with multiple stents versus a single stent. METHODS: The incidence of MACE (death, myocardial infarction, or target vessel revascularization) during long-term follow-up was investigated in 634 patients who underwent single-vessel PCI. Of the 634 patients, 319 (50%) had a single stent, and 315 (50%) had multiple stents inserted. Stepwise Cox regression analyses were performed to identify significant independent prognostic factors for MACE. RESULTS: At 47-month follow-up, MACE occurred in 61 of 319 patients (19%) who had a single stent versus in 57 of 315 patients (18%) who had multiple stents (P not significant). Significant independent predictors of MACE were use of vein grafts (hazard ratio = 1.94; 95% CI, 1.24-3.03; P = 0.0038) and use of drug-eluting stents (hazard ratio = 0.49; 95% CI, 0.34-0.72; P = 0.0002). CONCLUSIONS: At long-term follow-up of single-vessel PCI, the incidence of MACE was similar in patients with multiple or single stents inserted even after controlling for the length of stents.

Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients.

BACKGROUND: The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) reduce serum cholesterol level and cardiovascular morbidity and mortality. However, the effect of statins on glucose metabolism is unclear. Some studies have suggested that statins may cause hyperglycemia by increasing calcium concentration in the islet cells leading to decrease in insulin release or by decreasing GLUT 4-mediated peripheral glucose uptake. METHODS: We analyzed the data in 345,417 patients (mean age 61 +/- 15 years, 94% males, 6% diabetic, 20% statin users) from the Veterans Affairs VISN 16 database. We studied change in fasting plasma glucose (FPG) in this population over a mean time of 2 years between the first available measurement and the last measurement form the most recent recorded visit. Data were limited to patients who had 2 FPG measurements. Diagnosis of diabetes had to be present before the first FPG measurement. RESULTS: Among patients without diabetes, FPG increased with statin use from 98 mg/dL to 105 mg/dL, and among nonstatin users, FPG increased from 97 mg/dL to 101 mg/dL (increase in FPG with statin use P < 0.0001). Among patients with diabetes, FPG increased with statin use from 102 mg/dL to 141 mg/dL, and among nonstatin users, FPG increased from 100 mg/dL to 129 mg/dL (increase in FPG with statin use; P < 0.0001). After adjustment for age and use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors, the change in FPG in nondiabetic statin users was 7 mg/dL (vs 5 mg/dL in nonstatin users, P < 0.0001) and for diabetic statin users it was 39 mg/dL (vs 32 in nonstatin users, P < 0.0001). CONCLUSIONS: Statin use is associated with a rise of FPG in patients with and without diabetes. This relationship between statin use and rise in FPG is independent of age and use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors.

Effect of statins on the development of renal dysfunction.

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 > or =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.

Enhanced 11beta-hydroxysteroid dehydrogenase activity, the metabolic syndrome, and systemic hypertension.

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 11beta-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.

Relation of microalbuminuria and coronary artery disease in patients with and without diabetes mellitus.

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 > or = 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.

Prevalence of left ventricular hypertrophy in persons with and without obstructive sleep apnea.

We investigated the prevalence of left ventricular hypertrophy (LVH) in persons with and without obstructive sleep apnea (OSA). Fifty-three persons had a nocturnal polysomnogram to diagnose OSA and 2-dimensional echocardiograms to measure left ventricular mass. OSA was considered mild if the respiratory disturbance index (RDI) was 5 to 15, moderate if the RDI was 15 to 30, and severe if the RDI was >30. LVH was diagnosed if the left ventricular mass index was >110 g/m in women and >134 g/m in men. LVH was present in 21 of 27 persons (78%) with moderate or severe OSA, in 6 of 13 persons (46%) with mild OSA, and in 3 of 13 persons (23%) with no OSA (P < 0.001 comparing moderate or severe OSA with no OSA and P < 0.05 comparing moderate or severe OSA with mild OSA). OSA was a significant independent predictor of LVH after controlling the confounding effects of hypertension with an odds ratio of 3.579 (95% confidence interval, 1.589-8.058).

Electrocardiographic abnormalities in patients with right ventricular dilation due to acute pulmonary embolism.

In a study of 190 patients with acute pulmonary embolism, right ventricular dilation was present in 64 (34%), mean age 58 +/- 15 years. The 18 electrocardiographic abnormalities on the 12-lead electrocardiogram had a sensitivity of 8-69%, a specificity of 70-98%, a positive predictive value of 23-69%, a negative predictive value of 64-83%, a likelihood ratio for a positive test of 1.3-4.4, and a likelihood ratio for a negative test of 0.41-1.10 in predicting right ventricular dilation in patients with acute pulmonary embolism.

Prevalence of echocardiographic left ventricular hypertrophy in persons with systemic hypertension, coronary artery disease, and peripheral arterial disease and in persons with systemic hypertension, coronary artery disease, and no peripheral arterial disease.

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).

Left ventricular ejection fraction and prevalence of new left ventricular wall motion abnormality at long-term follow-up in patients with automatic implantable cardioverter-defibrillators treated with dual-chamber rate-responsive pacing at a rate of 70/minute versus backup ventricular pacing at a rate of 40/minute.

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).

Treatment of abdominal aortic aneurysms with an endovascular stent-graft prosthesis in 96 high-risk patients.

. Ninety-six patients, mean age 72 +/- 8 years, with an abdominal aortic aneurysm (AAA) and significant comorbidities with a vascular anatomy favorable for supporting an endovascular prosthesis underwent endovascular repair of the AAA. The 90-day survival was 100%. The incidence of endoleaks at 25-month mean follow up was 4 of 96 patients (4%). None of the 96 patients (0%) required surgical conversion of the AAA. At 14-month mean follow up after endovascular repair, the diameter of the AAA was significantly reduced from 6.2 +/- 1.2 cm to 5.0 +/- 1.1 cm (P < 0.001).

Clinical characteristics, risk factors, and medical treatment of 561 patients with peripheral arterial disease followed in an academic vascular surgery clinic.

The charts of all 561 patients (69% men and 31% women, mean age 71 +/- 10 years) with peripheral arterial disease (PAD) followed in an academic vascular surgery clinic were reviewed. Coexistent coronary artery disease (CAD) was present in 364 of 561 patients (65%). Of the 561 patients with PAD, 442 (79%) were current or exsmokers, 385 (69%) had hypertension, 225 (40%) had diabetes, 358 (64%) had a serum low-density lipoprotein (LDL) cholesterol > or =100 mg/dL, and 228 (41%) had a serum high-density lipoprotein cholesterol <40 mg/dL. Cilostazol or pentoxifylline was given to 301 of 301 patients (100%) with intermittent claudication. Aspirin or clopidogrel was given to 501 of 561 patients (89%) with PAD. Statins were given to 282 of 358 patients (79%) with PAD and an increased serum LDL cholesterol. If CAD was present, beta blockers were given to 301 of 364 patients (83%) and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers to 303 of 364 patients (83%).

Association of right ventricular dysfunction with in-hospital mortality in patients with acute pulmonary embolism and reduction in mortality in patients with right ventricular dysfunction by pulmonary embolectomy.

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 <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 <0.025 comparing pulmonary embolectomy with no pulmonary embolectomy).