Effects on insulin action of adding low-dose thiazide to angiotensin-converting enzyme inhibitor in essential hypertension.

Concern exists regarding adverse metabolic effects of antihypertensive agents. In the United States, diuretics are recommended first-line but additional agents, usually angiotensin-converting enzyme (ACE) inhibitors, are often required to meet blood pressure targets. We have previously shown that the combination of low-dose diuretic with an ACE inhibitor has detrimental effects on insulin action compared with ACE inhibitor alone in hypertensive type 2 diabetic patients. Our aim was to establish whether similar effects occur in nondiabetic hypertensive patients using this combination. A randomized double-blind placebo-controlled crossover design was used. After a 6-week run-in, when regular antihypertensive medications were withdrawn and placebo substituted, patients received captopril 50 mg twice daily with either bendroflumethiazide 1.25 mg (CB) or placebo (CP) for 12 weeks with a 6-week wash-out between treatments. Insulin action was assessed by hyperinsulinemic euglycemic clamp after the 6-week run-in and at the end of each treatment period. There were no differences between treatments in fasting glucose or insulin concentrations. Glucose infusion rates required to maintain euglycemia were the same with each treatment (CP 22.1±2.2 vs CB 22.2±2.2 µmol/kg per minute). There was no difference in endogenous glucose production in the basal state (CP 8.9±0.5 vs CB 9.5±0.7 µmol/kg per minute; P=0.23) or during hyperinsulinemia (CP 2.2±0.6 vs CB 1.5±0.3 µmol/kg per minute; P=0.30). In contrast to the situation in type 2 diabetes mellitus, ACE inhibitor combined with low-dose thiazide diuretic does not adversely affect insulin action when compared with ACE inhibitor alone in nondiabetic hypertensive patients.

Tissue harmonic imaging in echocardiography: better valve imaging, but at what cost?

BACKGROUND: Tissue harmonic imaging (THI) improves echocardiographic image quality and is widely utilized. Unfortunately it also makes structures appear artificially thickened. We sought to examine its impact on the imaging of left-sided heart valves. METHODS: A large echocardiographic database was searched for full, standard transthoracic echocardiographic exams performed 12-month periods before (n = 3,786) and after (n = 3,914) transition to THI at a single institution. Patients with prosthetic valves were excluded. RESULTS: The mean age of patients was 63 +/- 17 years and 65% were men. No appreciable difference in demographics was observed between time periods. While inadequate visualization of the mitral valve was reduced by 30% using THI (P = 0.014), reports of leaflet thickening increased by 28% (P = 0.005). Similarly, inadequate aortic valve visualization was reduced by 53% with THI (P < 0.001), at the expense of more aortic sclerosis (+6%, P = 0.034). Among the 480 patients with echocardiograms using each modality (time interval between studies: 370 +/- 143 days), THI did not appreciably improve visualization of the either valve. Although no significant increase in mitral thickness was seen with THI, aortic sclerosis was increased by at least one grade in 24.5% (P < 0.006). CONCLUSION: This study suggests that while THI enhances imaging of difficult to visualize valves, it may overestimate mitral and aortic valve thickness. This could lead to overdiagnosis and unnecessary follow-up studies. Cardiologists interpreting THI echocardiograms should become familiar with the modality's shortcomings.

Conversion to atorvastatin in patients intolerant or refractory to simvastatin therapy: the CAPISH study.

OBJECTIVE: To examine the safety and efficacy of switching from simvastatin to atorvastatin in patients who had either an inadequate lipid-lowering response with, or an adverse reaction to, simvastatin. PATIENTS AND METHODS: The Conversion to Atorvastatin in Patients Intolerant or Refractory to Simvastatin Therapy (CAPISH) study was designed in 2 parts: a retrospective cohort study of patients (group A), identified from a large pharmacy database, who converted from simvastatin to atorvastatin at a single academic military medical center (between April 1998 and March 2002) and a prospective cohort study of patients (group B) monitored in a lipid clinic at the same institution (between April 2002 and March 2003). Group A was identified by 2 or more simvastatin prescription fills and at least 1 atorvastatin prescription fill. Group B was identified by a physician-perceived need to switch from simvastatin to atorvastatin. Clinical, pharmaceutical, and laboratory records of both cohorts were reviewed. RESULTS: Approximately 1 in 4 simvastatin-treated patients discontinued therapy during a 4-year period. The most common reason for switching to atorvastatin was inadequate low-density lipoprotein (LDL) cholesterol control, although asymptomatic creatine kinase (CK) elevation and myalgias were also common. In most cases of myositis and in nearly all cases of rhabdomyolysis, patients were taking 80 mg of simvastatin. Achievement of National Cholesterol Education Program LDL cholesterol goals increased from 25% to 63% in group A and from 13% to 78% in group B, both P<.001. Significant reductions in CK also were seen in both groups. Adherence to atorvastatin was greater than 80% in both groups after 28.1+/-13.2 months (group A, 841 patients) and 8.1+/-3.8 months (group B, 104 patients). Among patients not taking atorvastatin at follow-up, 58% were no longer taking statins. CONCLUSION: Atorvastatin was well tolerated in patients who previously were taking simvastatin. Serum lipid panels were improved substantially and CK levels were decreased without compromise to patient safety.