NOCTURIA IN ELDERLY PEOPLE WITH HYPERTENSION—NO INFLUENCE OF LOW‐DOSE THIAZIDE ADDED TO LOSARTAN (2008)

To the Editor: Most guidelines recommend thiazide-type diuretics as the preferred initial drugs for the treatment of hypertension. Thiazides, used in lower doses in elderly people with hypertension, are useful especially when used with an angiotensin II receptor blocker (ARB), which can antagonize the potassium-excreting effect of thiazides. It is also reported that drug-related adverse reactions are lower when thiazide-type diuretics are added to ARB monotherapy than with other combinations.1,2 However, in these studies, consideration of the influence of thiazides on the geriatric syndrome is lacking. There could be a particular concern with regard to nocturia, a component of the geriatric syndrome that influences general health and quality of life (QOL) in elderly patients.3 Some epidemiological studies have reported that diuretics are one of the risk factors for urinary problems in elderly people.4 With this in mind, the effect of low-dose thiazide added to losartan monotherapy on nocturia in elderly hypertensives was examined. Fifteen elderly patients with hypertension (mean age ± standard deviation=76 ± 8, female/male=6/9) who had been receiving losartan monotherapy (50 or 100 mg/d) for more than 1 month and had systolic blood pressure (BP) of 140 mmHg or greater or diastolic BP of 90 mmHg or greater were enrolled. They did not have any history of heart failure or other cardiovascular disease. Hydrochlorothiazide (HCTZ) at 12.5 mg/d was added to losartan and maintained for 3 months. Other medication was unchanged during the study; four patients were taking a statin, one was taking a sulfonylurea, but no patient was taking medication for gout or an overactive bladder. BP was measured at home and in the doctor's office early in the morning. Laboratory tests were performed in the morning after an overnight fast, and questionnaires on nocturia and health-related QOL were given to all patients. As shown in Table 1, addition of low-dose HCTZ significantly reduced office BP after 1 month. The BP-lowering effect was sustained at 3 months and confirmed by morning home BP. No patient experienced worsening of nocturia during the study. On average, the frequency of nocturia was less at 1 month. At 3 months, the frequency of nocturia was similar to that at baseline. The result was unchanged if the subjects without nocturia were excluded from the analysis (1.3 ± 0.6 episodes/night at baseline to 1.2 ± 0.6 episodes/night after 3 months; n=11, P=.17). In the QOL questionnaire (visual analog scale graded 0–5), sufficiency of sleep (3.4 ± 1.5 to 3.3 ± 1.6) and satisfaction with health (3.1 ± 1.0 to 3.2 ± 0.9) did not change significantly during the study period. Although serum creatinine and uric acid were significantly higher after 3 months, the changes were slight, and no subject showed an abnormal rise beyond the normal range. Fasting plasma glucose, serum total cholesterol, triglycerides, urea nitrogen, and potassium did not change significantly (Table 1 and data not shown). This study is preliminary in terms of its size and noncontrolled design, but the results suggest that addition of low-dose HCTZ to losartan monotherapy effectively inhibits BP without worsening of nocturia in elderly people with hypertension. Because an ARB/thiazide combination is one of the most frequently prescribed regimens, the findings of the present study may provide useful information on urinary problems in elderly people with hypertension. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this letter. Author Contributions: T.K.: study design, analysis and interpretation of data, and preparation of manuscript. M.A.: study concept and design, and preparation of manuscript. M.E. and K.I.: acquisition of subjects. Y.O.: study concept and design. Sponsor's Role: None.