Metabolic issues in the antihypertensive and lipid-lowering heart attack trial study

Abstract

Based on the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ALLHAT) Trial, the Seventh Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) states that "thiazide-type diuretics should be used as initial therapy for most patients with hypertension." In the ALLHAT study, although there was no difference in the primary outcome for fatal heart attack and nonfatal myocardial infarction between all treatment groups, the manuscript endorses thiazide-type diuretics as first choice, based on their cardioprotective effects and low cost. It is well known that thiazide-type diuretics cause hypokalemia, glucose intolerance, and diabetes, although the ALLHAT study showed a significant 43% to 65% higher risk of new-onset diabetes with chlorthalidone compared with amlodipine (30%) and lisinopril (18%). The investigators justified the fact that the greater incidence of diabetes did not translate into more cardiovascular events. Such a conclusion ignores that the morbidity and mortality from diabetes manifests over decades and not the mere 2- to 6-year time frame examined in the ALLHAT study. It would appear that the strong endorsement of thiazide-type diuretics as first-line therapy by the JNC-7 will lead to a higher incidence of diabetes in these patients.

Thiazide Diuretics, Potassium, and the Development of Diabetes

“…3,5,24,25 In ALLHAT, development of diabetes occurred significantly more in the thiazide group with an absolute difference of 1.8% to 3.5% relative to the lisinopril and amlodipine groups (PϽ0.05). In other clinical trials, the absolute difference of new-onset diabetes was 2.1% and 1.6% higher in the thiazide diuretic groups compared with ACE inhibitor or CCB groups.…”

“…1 Some have argued that the follow-up period of 4.9 years (range, 4 to 8 years) was not adequate to account for the occurrence of cardiovascular outcomes among those patients who developed diabetes while receiving antihypertensive treatment. 3,4 Reports by Verdecchia et al 5,6 seem to support this view. They observed that treatment with thiazide diuretics was an independent predictor of new diabetes among patients with hypertension, followed for a median of 6 years (range, 1 to 16 years).…”

Precision measurements of the top quark mass from the Tevatron in the pre-LHC era

“…All M t measurements which utilized this technique so far lacked a consistent likelihood formulation owing to the absence of the resolution prior, as discussed in detail in [137]. Perhaps, this is the reason why such measurements did not demonstrate convincing uncertainty improvements over results obtained with templates.…”

Observation of the rare decayB+→K+π0π0and measurement of the quasi-two-body contributionsBLees1, Poireau2, Tisserand3 et al. 2011Phys. Rev. D202160View full textAdd to dashboardCite

“…Prior to the selection of multiple candidates (see below), we make the requirement |∆E| < 0.30 GeV, in order to retain sidebands for background studies. However, to avoid possible biases [31] we do not use ∆E in the fit described below and instead apply tighter selection criteria for events entering the fit, −0.15 GeV < ∆E < 0.05 GeV. These criteria have an efficiency of about 80 % for signal while retaining only about 30 % of the background, both compared to the looser requirement |∆E| < 0.30 GeV.…”