Hydrochlorothiazide vs chlorthalidone, indapamide, and potassium-sparing/hydrochlorothiazide diuretics for reducing left ventricular hypertrophy: A systematic review and meta-analysis.

Left ventricular hypertrophy develops in 36%-41% of hypertensive patients and independently predicts cardiovascular events and total mortality. Moreover, drug-induced reduction in left ventricular mass (LVM) correlates with improved prognosis. The optimal thiazide-type diuretic for reducing LVM is unknown. Evidence regarding potency, cardiovascular events, sodium, and potassium suggested the hypothesis that "CHIP" diuretics (CHlorthalidone, Indapamide, and Potassium-sparing diuretic/hydrochlorothiazide [PSD/HCTZ]) would reduce LVM more than HCTZ. Systematic searches of five databases were conducted. Among the 38 randomized trials, a 1% reduction in systolic blood pressure (SBP) predicted a 1% reduction in LVM, P = 0.00001. CHIP-HCTZ differences in reducing LVM differed across trials (ie, heterogeneity), making interpretation uncertain. However, among the 28 double-blind trials, heterogeneity was undetectable, and HCTZ reduced LVM (percent reduction [95% CI]) by -7.3 (-10.4, -4.2), P < 0.0001. CHIP diuretics surpassed HCTZ in reducing LVM: chlorthalidone -8.2 (-14.7, -1.6), P = 0.015; indapamide -7.5 (-12.7, -2.3), P = 0.005; and all CHIP diuretics combined -7.7 (-12.2, -3.1), P < 0.001. The comparison of PSD/HCTZ with HCTZ had low statistical power but favored PSD/HCTZ: -6.0 (-14.1, +2.1), P = 0.149. Thus, compared to HCTZ, CHIP diuretics had twice the effect on LVM. CHIP diuretics did not surpass HCTZ in reducing systolic or diastolic blood pressure: -0.3 (-5.0, +4.3) and -1.6 (-5.6, +2.4), respectively. The strength of evidence that CHIP diuretics surpass HCTZ for reducing LVM was high (GRADE criteria). In conclusion, these novel results have demonstrated that CHIP diuretics reduce LVM 2-fold more than HCTZ among hypertensive patients. Although generally related to LVM, blood pressure fails to explain the superiority of CHIP diuretics for reducing LVM.

Does Caffeine Consumption Increase the Risk of New-Onset Atrial Fibrillation?

OBJECTIVE: Caffeine has been considered a trigger for atrial fibrillation (AF). We conducted a meta-analysis including a dose-response analysis to assess the relationship between caffeine consumed and incidence of AF. METHODS: Data from selected studies represented 176,675 subjects (AF in 9,987 [5.7%]). Caffeine content varied widely, ranging from 40 to 180 mg per cup of coffee. For purposes of the calculations in this study, we assumed 140 mg of caffeine in a standard 12-oz cup of coffee. RESULTS: No significant difference was found in AF incidence when the subjects consuming less than 2 cups of coffee per day were compared to subjects with higher consumption, 1.068 (0.937-1.216). The risk of AF was higher among subjects consuming less than 2 cups of coffee daily when compared to higher daily consumption subjects. A lower incidence of AF was found among people consuming more than 436 mg daily. CONCLUSION: The incidence of AF is not increased by coffee consumption. In fact, we found a lower incidence of AF when caffeine consumption exceeded 436 mg/day. Therefore, based on available evidence there is no association between caffeine intake and AF risk.

Hydrochlorothiazide and alternative diuretics versus renin-angiotensin system inhibitors for the regression of left ventricular hypertrophy: a head-to-head meta-analysis.

BACKGROUND: Found in 36-41% of hypertension, elevated left ventricular mass (LVM) independently predicts cardiovascular events and total mortality. Conversely, drug-induced regression of LVM predicts improved outcomes. Previous studies have favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives for reducing LVM but ignored differences among thiazide-type diuretics. From evidence regarding potency, cardiovascular events, and electrolytes, we hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for reducing LVM. METHOD AND RESULTS: Systematic review yielded 12 relevant double-blind randomized trials. CHIPs were more closely associated with reduced LVM than HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic separately. Publication bias favoring RASIs was corrected by cumulative analysis. For reducing LVM, HCTZ tended to be less effective than RASIs. However, the following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to -0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002. Statistical significance (P < 0.05) did not depend on any one trial. CHIPs reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended to increase with trial duration, from a negligible effect at 0.5 year to a maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight percent of patients had information on echocardiographic components of LVM: relative to RASIs, CHIPs significantly reduced end-diastolic LV internal dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence favoring CHIPs over RASIs was at least moderate. CONCLUSION: In these novel results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and EDLVID.

Quality of Meta-Analyses for Randomized Trials in the Field of Hypertension: an Updated and Improved Systematic Review.

Publications of hypertension-related meta-analyses (MAs) have increased exponentially in the past 25 years and now average 8/month. Theoretically, this is facilitating evidence-based management of patients. However, some practitioners and authors of guidelines have questioned the quality of published MAs. By extending a prior review, we have assessed the quality of 212 hypertension-related meta-analyses over 5 years based on systematically searching three computerized libraries. Seventeen criteria grouped into four domains of quality yielded the following results: (1) Assessment of trial quality was accomplished in 89% of MAs, and 38% analyzed trials in subgroups of trial quality where appropriate. (2) All three measures of heterogeneity (I 2, tau, and P for heterogeneity) were reported in 36%, reflecting the failure to report tau, the standard deviation of the main effect. (3) Publication bias was assessed in 75%, and 43% of MAs used a statistical test for publication bias. (4) Regarding transparency, 9 to 31% of MAs reported problems in the previous three domains in the article's abstract. Journal impact factor reporting the MAs declined significantly over 5 years. The percent with criteria of quality in a MA was modestly correlated with journal impact factor (R 2 = 0.05, P = 0.001). False-positive results from inappropriate application of the DerSimonian-Laird model affected 25% of articles, which reported these false positives in the article's abstract in 72%. No more than 25% of MAs had 67% or more of the criteria of quality. In conclusion, skepticism of hypertension-related MAs is justified, but their quality can be readily corrected.

Psychological impact of electrocardiogram screening in National Collegiate Athletic Association athletes.

PURPOSE: Determine the psychological impact of false-positive ECG screening in National Collegiate Athletic Association (NCAA) athletes. METHODS: Athletes representing seven NCAA institutions received a standardised history, physical examination and ECG interpreted using the 2013 Seattle Criteria. Assessments of health attitudes, anxiety and impact of screening on sport were conducted using validated prescreen and postscreen measurements. RESULTS: 1192 student-athletes participated (55.4% male, median age 19 years, 80.4% Caucasian). 96.8% of athletes had a normal cardiovascular screen, 2.9% had a false-positive ECG and 0.3% were diagnosed with a serious cardiac condition. Prior to screening, 4.5% worried about potentially harbouring cardiac disease and 70.1% preferred knowing about an underlying condition, rather than play sports without this knowledge. There was no difference in anxiety described by athletes with a normal versus false-positive screen (p=0.369). Reported anxiety levels during screening also did not differ when analysed by different gender, race, division of play or sport. Athletes with normal and false-positive screens had similar levels of satisfaction (p=0.714) and would recommend ECG screening to other athletes at similar rates (p=0.322). Compared with athletes with a normal screen, athletes with false-positive results also reported feeling safer during competition (p>0.01). In contrast, athletes with false-positive screens were more concerned about the possibility of sports disqualification (p<0.001) and the potential for developing a future cardiac condition (p<0.001). CONCLUSIONS: Athletes with a false-positive ECG do not experience more anxiety than athletes with a normal screen but do express increased concern regarding sports disqualification and the development of a cardiac disorder. These findings do not justify avoiding advanced cardiovascular screening protocols. Further understanding of athlete experiences could better prepare the practising physician to counsel athletes with an abnormal ECG.

Hypertrophic Cardiomyopathy as a Cause of Sudden Cardiac Death in the Young: A Meta-Analysis.

BACKGROUND: Sudden cardiac death is often linked with hypertrophic cardiomyopathy in young athletes, but with a divergence of study results. We performed a meta-analysis to compare the prevalence of sudden cardiac deaths associated with hypertrophic cardiomyopathy vs sudden cardiac deaths associated with structurally normal hearts. METHODS: A structured search of MEDLINE was conducted for studies published from 1990 through 2014. Retrospective cohort studies, patient registries, and autopsy series examining sudden cardiac death etiology in young individuals (age ≤35 years) were included. A random-effects model was applied to generate pooled summary estimates of the percentage of sudden cardiac deaths with structurally normal hearts at postmortem vs those caused by hypertrophic cardiomyopathy. Heterogeneity was assessed using I(2). Subgroup analyses were conducted based on study location, patient age groups, and population types. RESULTS: Thirty-four studies were included, representing a combined sample of 4605 subjects. The overall pooled percentage of sudden cardiac deaths caused by hypertrophic cardiomyopathy was 10.3% (95% confidence interval [CI], 8.0%-12.6%; I(2) = 87.2%), while sudden cardiac deaths with structurally normal hearts at death were more common (P <.001) at 26.7% (95% CI, 21.0%-32.3%; I(2) = 95.3%). In nonathlete subjects, the pooled percentage of sudden cardiac deaths associated with structurally normal hearts (30.7%; 95% CI, 23.0%-38.4%; I(2) = 96.3%) were significantly more common (P <.001) than sudden cardiac death caused by hypertrophic cardiomyopathy (7.8%; 95% CI, 5.8%-9.9%; I(2) = 80.1%). Among athletes, there was no significant difference between summary estimates of hypertrophic cardiomyopathy and structurally normal hearts (P = .57), except in Europe where structurally normal hearts were more common (P = .01). CONCLUSIONS: Hypertrophic cardiomyopathy is not a more common finding at death than structurally normal hearts in young subjects with sudden cardiac death. Increased attention should be directed toward identifying causes of death associated with a structurally normal heart in subjects with sudden cardiac death.

Are the QRS duration and ST depression cut-points from the Seattle criteria too conservative?

BACKGROUND: Screening athletes with ECGs is aimed at identifying "at-risk" individuals who may have a cardiac condition predisposing them to sudden cardiac death. The Seattle criteria highlight QRS duration greater than 140 ms and ST segment depression in two or more leads greater than 50 µV as two abnormal ECG patterns associated with sudden cardiac death. METHODS: High school, college, and professional athletes underwent 12 lead ECGs as part of routine pre-participation physicals. Prevalence of prolonged QRS duration was measured using cut-points of 120, 125, 130, and 140 ms. ST segment depression was measured in all leads except leads III, aVR, and V1 with cut-points of 25 µV and 50 µV. RESULTS: Between June 2010 and November 2013, 1595 participants including 297 (167 male, mean age 16.2) high school athletes, 1016 (541 male, mean age 18.8) college athletes, and 282 (mean age 26.6) male professional athletes underwent screening with an ECG. Only 3 athletes (0.2%) had a QRS duration greater than 125 ms. ST segment depression in two or more leads greater than 50 µV was uncommon (0.8%), while the prevalence of ST segment depression in two or more leads increased to 4.5% with a cut-point of 25 µV. CONCLUSION: Changing the QRS duration cut-point to 125 ms would increase the sensitivity of the screening ECG, without a significant increase in false-positives. However, changing the ST segment depression cut-point to 25 µV would lead to a significant increase in false-positives and would therefore not be justified.