N.E.B. Kohlmann

Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertension

SUMMARY

Serum Insulin Levels, 24-Hour Blood Pressure Profile, and Left Ventricular Mass in Nonobese Hypertensive Patients

In essential hypertensive patients, considered to be insulin-resistant, a blunted decline in nocturnal blood pressure is associated with increased adrenergic tone and left ventricular mass. Since insulin stimulates the sympathetic system, we tested whether insulin resistance and insulinemia influence left ventricular mass and the 24-hour blood pressure profile. We studied 29 nonobese hypertensive patients with office diastolic pressure between 95 and 110 mm Hg and normal oral glucose tolerance test after a 4-month washout period. They were then assigned to M-mode echocardiographic evaluation and 24-hour ambulatory blood pressure monitoring. The glucose and insulin responses to a 75-g oral glucose load were compared with those obtained in 16 weight-matched normotensive control subjects. During the oral glucose tolerance test the hypertensive patients compared with control subjects presented higher levels of glucose at 60 minutes (138.7 +/- 30.3 versus 108.7 +/- 35.7 mg/dL; P < .05) and 90 minutes (114.0 +/- 23.8 versus 94.8 +/- 31.1 mg/dL; P < .05) and insulin at 60 minutes (287.1 +/- 259.4 versus 142.1 +/- 83.9 pmol/L; P < .05). However, peak insulin levels after glucose load did not correlate with ambulatory blood pressure values or left ventricular mass index. Left ventricular mass index showed significant correlation with mean sleeping systolic pressure (rs = 56, P < .05) and diurnal systolic pressure (rs = .37, P < .05) but not with mean diurnal or sleeping diastolic pressures. In conclusion, our results indicate that in nonobese hypertensive patients, insulin resistance does not have any influence on the 24-hour blood pressure profile or on left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Nocturnal blood pressure fall as predictor of diabetic nephropathy in hypertensive patients with type 2 diabetes

BackgroundHypertensive patients with reduced blood pressure fall (BPF) at night are at higher risk of cardiovascular events (CVE).MethodsWe evaluated in hypertensive diabetic patients, if a reduced nocturnal BPF can precedes the development of diabetic nephropathy (DN). We followed 70 patients with normal urinary albumin excretion (UAE) for two years. We performed 24-hours ambulatory BP monitoring in baseline and at the end of the study.ResultsFourteen (20%) patients (GI) developed DN (N = 11) and/or CVE (n = 4). Compared to the remaining 56 patients (GII) in baseline, GI had similar diurnal systolic (SBP) and diastolic BP (DBP), but higher nocturnal SBP (138 ± 15 vs 129 ± 16 mmHg; p < 0.05) and DBP (83 ± 12 vs 75 ± 11 mmHg; p < 0,05). Basal nocturnal SBP correlated with occurrence of DN and CVE (R = 0.26; P < 0.05) and with UAE at the end of the study (r = 0.3; p < 0.05). Basal BPF (%) correlated with final UAE (r = -0.31; p < 0.05). In patients who developed DN, reductions occurred in nocturnal systolic BPF (12 ± 5 vs 3 ± 6%, p < 0,01) and diastolic BPF (15 ± 8 vs 4 ± 10%, p < 0,01) while no changes were observed in diurnal SBP (153 ± 17 vs 156 ± 16 mmHg, NS) and DBP (91 ± 9 vs 90 ± 7 mmHg, NS). Patients with final UAE < 20 μg/min, had no changes in nocturnal and diurnal BP.ConclusionsOur results suggests that elevations in nocturnal BP precedes DN and increases the risk to develop CVE in hypertensive patients with T2DM.

Effects of Sibutramine on the Treatment of Obesity in Patients with Arterial Hypertension

OBJECTIVE To assess the effects of weight reduction with 10mg of sibutramine or placebo on blood pressure during 24 hours (ambulatory blood pressure monitoring), on left ventricular mass, and on antihypertensive therapy in 86 obese and hypertensive patients for 6 months. METHODS The patients underwent echocardiography, ambulatory blood pressure monitoring, and measurement of the levels of hepatic enzymes prior to and after treatment with sibutramine or placebo. RESULTS The group using sibutramine had a greater weight loss than that using placebo (6.7% versus 2.5%; p<0.001), an increase in heart rate (78.3 +/- 7.3 to 82 +/- 7.9 bpm; p=0.02), and a reduction in the left ventricular mass/height index (105 +/- 29.3 versus 96.6 +/- 28.58 g/m; p=0.002). Both groups showed similar increases in the levels of alkaline phosphatase and comparable adjustments in antihypertensive therapy; blood pressure, however, did not change. CONCLUSION The use of sibutramine caused weight loss and a reduction in left ventricular mass in obese and hypertensive patients with no interference with blood pressure or with antihypertensive therapy.

Left Ventricular Hypertrophy Evaluation in Obese Hypertensive Patients: Effect of Left Ventricular Mass Index Criteria

PURPOSE To evaluate left ventricular mass (LVM) index in hypertensive and normotensive obese individuals. METHODS Using M mode echocardiography, 544 essential hypertensive and 106 normotensive patients were evaluated, and LVM was indexed for body surface area (LVM/BSA) and for height2 (LVM/h2). The 2 indexes were then compared in both populations, in subgroups stratified according to body mass index (BMI): <27; 27-30; >/= 30kg/m2. RESULTS The BSA index does not allow identification of significant differences between BMI subgroups. Indexing by height2 provides significantly increased values for high BMI subgroups in normotensive and hypertensive populations. CONCLUSION Left ventricular hypertrophy (LVH) has been underestimated in the obese with the use of LVM/BSA because this index considers obesity as a physiological variable. Indexing by height2 allows differences between BMI subgroups to become apparent and seems to be more appropriate for detecting LVH in obese populations.

Left Ventricular Diastolic Function in Essential Hypertensive Patients. Influence of Age and Left Ventricular Geometry

PURPOSE To evaluate diastolic dysfunction (DD) in essential hypertension and the influence of age and cardiac geometry on this parameter. METHODS Four hundred sixty essential hypertensive patients (HT) underwent Doppler echocardiography to obtain E/A wave ratio (E/A), atrial deceleration time (ADT), and isovolumetric relaxation time (IRT). All patients were grouped according to cardiac geometric patterns (NG - normal geometry; CR - concentric remodeling; CH- concentric hypertrophy; EH - eccentric hypertrophy) and to age (<40; 40 - 60; >60 years). One hundred six normotensives (NT) persons were also evaluated. RESULTS A worsening of diastolic function in the HT compared with the NT, including HT with NG (E/A: NT - 1.38+/-0.03 vs HT - 1.27+/-0.02, p<0.01), was observed. A higher prevalence of DD occurred parallel to age and cardiac geometry also in the prehypertrophic groups (CR). Multiple regression analysis identified age as the most important predictor of DD (r2=0.30, p<0.01). CONCLUSION DD was prevalent in this hypertensive population, being highly affected by age and less by heart structural parameters. DD is observed in incipient stages of hypertensive heart disease, and thus its early detection may help in the risk stratification of hypertensive patients.

Blood pressure and cardiorenal responses to antihypertensive therapy in obese women

OBJECTIVE Blood pressure (BP) and target organ responses to antihypertensive drugs are not well established in hypertensive obese patients. This study is aimed at evaluating the effects of obesity and adiposity distribution patterns on these responses. METHODS 49 hypertensive obese women were designated to different groups according to waist to hip ratio measurements--37 with troncular and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine combination therapy to achieve a BP lower than 140/90 mmHg. Ambulatory blood pressure monitoring (ABPM), echocardiography, and albuminuria were assessed before and after the intervention. RESULTS After 24 weeks, weight loss was less than 2% in both groups. ABPM targets were achieved in 81.5% of patients upon a combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP: -22.5/-14.1(troncular obesity)/-23.6/-14.9 mmHg (peripheral obesity) were obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients. Upon BP control, microalbuminuria was markedly decreased, while only slight decrease in left ventricular mass was observed for both groups. CONCLUSIONS In the absence of weight loss, most patients required combined antihypertensive therapy to control their BP, regardless of their body fat distribution pattern. Optimal target BP and normal albuminuria were achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude.