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By Louis Kuritzky, MD
Effects of Losartan on Cardiovascular Morbidity and Mortality in Patients with Isolated Systolic Hypertension and LVH
Since the early 1990s it has been recognized that left ventricular hypertrophy (LVH) is an important prognostic indicator for cardiovascular morbidity and mortality. More recently, it has been suggested that angiotensin receptor blockers (ARBs) might exert a particularly favorable effect upon LVH, perhaps even independent of blood pressure (BP) effects. The LIFE (Losartan Intervention for Endpoint Reduction) study was designed to test the hypothesis that losartan (LSN) exerts preventive cardiovascular effects, beyond simply controlling BP. To this end, a randomized, controlled trial (n = 1326) of LSN vs atenolol (ATN) was initiated in persons with isolated systolic hypertension and LVH, with a primary composite end point of cardiovascular death, stroke, and MI.
Despite the fact that BP reduction was equal in both groups (28/9 mm Hg), there was a 25% relative risk reduction in the primary end point (CV death, stroke, MI) in favor of losartan. Additionally, LVH reduction was much more vigorously achieved by LSN than ATN. Stroke reduction was particularly favorably affected by LSN, in which a 40% reduction compared to ATN was seen. Lastly, LSN demonstrated a more favorable tolerability profile than ATN: discontinuations due to drug-related events were half as frequent in recipients of LSN than ATN.
Kjeldsen SE, et al. JAMA. 2002;1491-1498.
Increase in Nocturnal Blood Pressure and Progression to Microalbuminuria in Type 1 Diabetes
It has been noted that among persons with type 1 diabetes (DM-1), hypertension (HTN) often develops concomitantly with occurrence of microalbuminuria (MAU). Closer investigation with ambulatory BP monitoring (ABPM) suggests that nocturnal blood pressure elevations (NBP) are particularly associated with MAU; however, whether the NBP causes the MAU (or they are concomitant) has been uncertain.
Lurbe and associates prospectively studied ABPM in adolescent DM-1 patients (n = 75) who were normoalbuminuric and normotensive at enrollment. Subjects were periodically monitored by ABPM and urinary albumin measurements for more than 5 years. MAU developed in 19% of study subjects, and was preceded by a modest elevation in BP, but it was only the NBP in which change was manifest. Over time, in the group that ultimately developed MAU, the NBP increased by 5 mm Hg compared to baseline; in the normoalbuminuric group, NBP did not change. The subtlety of these findings is reflected by the fact that neither office BP, nor mean daytime BP predicted MAU. Hence, ABPM may detect modest BP patterns, which lead to early prediction of target organ damage.
Lurbe E, et al. N Engl J Med. 2002;347:797-805.
HRT, Lipid, and Glucose Metabolism in Diabetic and Nondiabetic Postmenopausal Women
Like cardiovascular diseases, type 2 diabetes (DM-2) increases in postmenopausal women. Prospective randomized interventional trials have not shown a benefit for hormone replacement therapy (HRT) in improving cardiovascular outcomes. The effect of HRT upon lipids and glucose among diabetic populations has been little studied. Crespo and colleagues evaluated subjects (n = 2786) in the Third National Health and Nutrition Examination Survey (NHANES III) seeking the relationship between HRT, diabetes, and lipids.
In diabetic women, total cholesterol and non-HDL levels were significantly lower in women who used HRT than never users, but there was no difference in HDL levels. In contrast, in nondiabetic women HDL levels were higher in HRT users than nonusers. Fasting glucose levels (FBS) in diabetic women were significantly lower in HRT recipients than never users (112 mg/dL vs > 150 mg/dL). Crespo et al conclude that menopausal HRT is associated with improved FBS, total cholesterol, and non-HDL in diabetics. The fact that these findings are observational in nature suggests cautious interpretation until their clinical relevance is ascertained through interventional trials. It may be that other, undetected factors in women who choose to use HRT are influencing lipid and glucose metabolism.
Crespo CJ, et al. Diabetes Care. 2002;25:1675-1680.
Dr. Kuritzky, Clinical Assistant Professor, University of Florida, Gainesville, is Associate Editor of Internal Medicine Alert.