Wijnanda J. Frenkel

Validation of the Charlson Comorbidity Index in acutely hospitalized elderly adults: a prospective cohort study.

To determine whether the Charlson Comorbidity Index (CCI) predicts short‐ and long‐term mortality.

Effects of thiazide-type and thiazide-like diuretics on cardiovascular events and mortality: systematic review and meta-analysis.

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes (P<0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events (P=0.049) and a 21% additional risk reduction for heart failure (P=0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.

The association between serum sodium levels at time of admission and mortality and morbidity in acutely admitted elderly patients: a prospective cohort study.

To the Editor: Throughout life, serum sodium level is maintained within narrow limits despite continuous variations in water and salt intake. Renal sodium transporters and osmoreceptors in the hypothalamus that control secretion of antidiuretic hormone (ADH) and regulate thirst are the main governors of sodium and water homeostasis. Disturbances in water and sodium homeostasis are frequently observed in elderly patients and, when severe, may lead to loss of consciousness, coma, or even death. Deviations in serum sodium have been associated with mortality and functional decline, but the association with functional decline has, to the knowledge of the authors, never been prospectively examined. The present study assessed the association between deviations in serum sodium levels at time of admission and 3-month mortality and functional decline in acutely admitted elderly patients.

Test characteristics of the aldosterone-to-renin ratio as a screening test for primary aldosteronism

Background: The aldosterone-to-renin ratio (ARR) is a widely used screening test for primary aldosteronism. Current guidelines recommend a cut-off value of 91 pmol/mU. Studies on its sensitivity, specificity, reproducibility and the role of medication have been conflicting. We prospectively assessed the test characteristics of the ARR and the effect of combination antihypertensive treatment. Methods: In 178 patients with persistent hypertension despite the use of at least two antihypertensives, plasma renin and aldosterone were assessed twice within an interval of 4 weeks. All patients underwent an intravenous salt loading test. A posttest plasma aldosterone exceeding 235 pmol/l was considered diagnostic for primary aldosteronism. ARR was repeated after 4 weeks of standardized treatment with a calcium channel blocker and/or &agr;-adrenergic-receptor blocker. Results: The prevalence of primary aldosteronism was 15.2%. The median ARR was 35.0 (interquartile range 16.2–82.0) in primary aldosteronism versus 7.1 (2.2–17.5) pmol/mU in essential hypertensive patients (P < 0.001). Under random medication, the ARR had 22.2% sensitivity and 98.7% specificity. On standardized treatment, the ARR rose from 9.6 (2.5–24.8) to 21.4 (10.8–52.1) (P < 0.001). Multivariate regression showed that angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II-receptor blockers were responsible for the lower ARR during random treatment. The area under the receiver operating characteristic curve was, however, similar under random and standardized treatment (84 vs. 86%, respectively, P = 0.314). Bland–Altman plots showed an almost five-fold difference in ARR values taken under the same conditions. Conclusion: ARR sensitivity for primary aldosteronism is low when the recommended cut-off is used. Reproducibility is also poor, stressing the need for alternative screening tests.

Determinants of blood pressure reduction by eplerenone in uncontrolled hypertension

Background: Add-on therapy with aldosterone receptor antagonists has been reported to lower blood pressure (BP) in patients with uncontrolled hypertension. We assessed potential predictors of this response. Methods: In essential hypertensive patients with uncontrolled BP, despite the use of at least two antihypertensives, plasma renin and aldosterone concentrations and the transtubular potassium gradient (TTKG) were measured. Patients were treated with eplerenone 50 mg daily on top of their own medication. The office and ambulatory BP response and biochemical changes were evaluated after 1 week and 3 months of treatment and 6 weeks after discontinuation. Potential predictors for the change in 24-h ambulatory BP were tested in a multivariate regression model. Results: One hundred and seventeen patients with a mean age of 50.5 ± 6.6 years were included. Office BP decreased from 149/91 to 142/87 mmHg (P < 0.001) and ambulatory BP from 141/87 to 132/83 mmHg after 3 months of treatment (P < 0.001). Six weeks after discontinuation of eplerenone, office and ambulatory BP measurements returned to baseline values. Treatment resulted in a small rise in serum potassium and creatinine, and a small decrease in the TTKG. In a multivariate model, neither renin, aldosterone, or their ratio, nor the TTKG predicted the BP response. Only baseline ambulatory SBP predicted the BP response, whereas the presence of left ventricular hypertrophy was associated with a smaller BP reduction. Conclusion: Add-on therapy with eplerenone effectively lowers BP in patients with difficult-to-treat primary hypertension. This effect is unrelated to circulating renin–angiotensin–aldosterone system activity and renal mineralocorticoid receptor activity as assessed by the TTKG.

Acute and chronic diseases as part of multimorbidity in acutely hospitalized older patients

BACKGROUND To describe the prevalence of multimorbidity and to study the association between acute and chronic diseases in acutely hospitalized older patients METHODS Prospective cohort study conducted between 2006 and 2008 in three teaching hospitals in the Netherlands. 639 patients aged 65 years and older, hospitalized for >48 h were included. Two physicians scored diseases, using ICD-9 codes. Chronic multimorbidity was defined as the presence of ≥2 chronic diseases, and acute multimorbidity as ≥1 acute diseases upon pre-existent chronic diseases. Logistic regression analyses were conducted to analyse cluster associations between a chronic index disease and the concurrent chronic or acute disease, corrected for age and sex. RESULTS The mean age of patients was 78 years, over 50% had ADL impairments. Prevalence of chronic multimorbidity was 69%, and acute multimorbidity was present in 88%. Hypertension (OR 1.16; 95% CI 1.08-1.24), diabetes (type I or type 2) (OR 1.12; 95% CI 1.04-1.21), heart failure (OR 1.25; 95% CI 1.14-1.38) and COPD (OR 1.19; 95% CI 1.05-1.34) were associated with acute renal failure. Hypertension (OR 1.10; 95% CI 1.04-1.17) and atrial fibrillation (OR 1.17; 95% CI 1.08-1.27) were associated with an adverse drug event. Gastro-intestinal bleeding was clustered with atrial fibrillation (OR 1.11; 95% CI 1.04-1.19) and gastric ulcer (OR 1.16; 95% CI 1.07-1.25). CONCLUSION Both acute and chronic multimorbidity was frequently present in hospitalized older patients. We identified specific associations between acute and chronic diseases. There is a need for strategies addressing multimorbidity during the exacerbation of chronic diseases.

Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and Mortality

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes (P<0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events (P=0.049) and a 21% additional risk reduction for heart failure (P=0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.

The predictive value of the Cockcroft-Gault formula and the modification of diet in renal disease formula for mortality in elderly people

To the Editor: Estimating the renal function of acutely admitted patients contributes to the assessment of their prognosis, because impaired renal function is associated with greater risk of morbidity and mortality. The clearance of (endogenous) creatinine is frequently used to estimate glomerular filtration rate (GFR). Currently, the CockcroftGault (CG) and the Modification of Diet in Renal Disease (MDRD) are the most commonly used formulas to predict creatinine clearance. In the current study, which method of estimating renal function has the highest predictive value for mortality in patients aged 65 and older acutely admitted to the internal medicine ward of a tertiary hospital was evaluated.

Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and MortalityNovelty and Significance

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes (P<0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events (P=0.049) and a 21% additional risk reduction for heart failure (P=0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.

Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and MortalityNovelty and Significance: Systematic Review and Meta-Analysis

Thiazide diuretics are recommended as first-line therapy for hypertension and are among the most commonly prescribed drugs worldwide. According to their molecular structure, thiazide diuretics can be divided in thiazide-type (TT) and thiazide-like (TL) diuretics. TL diuretics have a longer elimination half-life compared with TT diuretics and have been shown to exert additional pharmacological effects, which may differently affect cardiovascular risk. In this meta-analysis, we compared the effects of TT and TL diuretics on cardiovascular events and mortality. Randomized, controlled studies in adult hypertensive patients that compared TT or TL diuretics with placebo or antihypertensive drugs and had ≥1 year follow-up were included. Primary outcome was cardiovascular events; secondary outcomes included coronary events, heart failure, cerebrovascular events, and all-cause mortality. Meta-regression analysis was used to identify confounders and correct for the achieved blood pressure reductions. Twenty-one studies with >480 000 patient-years were included. Outcomes were not affected by heterogeneity in age, sex, and ethnicity among included studies, whereas larger blood pressure reductions were significantly associated with increased risk reductions for all outcomes (P<0.001). Corrected for differences in office blood pressure reductions among trials, TL diuretics resulted in a 12% additional risk reduction for cardiovascular events (P=0.049) and a 21% additional risk reduction for heart failure (P=0.023) when compared with TT diuretics. The incidence of adverse events was comparable among TT, TL diuretics, and other antihypertensive therapy. Our data suggest that the best available evidence seems to favor TL diuretics as the drug of choice when thiazide treatment is considered for hypertension.