Trandolapril, but not verapamil nor their association, restores the physiological renal hemodynamic response to adrenergic activation in essential hypertension.

The purpose of this study was to evaluate the effects of antihypertensive drugs on renal hemodynamics in hypertensive patients during an adrenergic activation by mental stress (MS), which induces renal vasoconstriction in healthy subjects. Renal hemodynamics was assessed twice in 30 middle-aged essential hypertensive patients (57±6 years)-after 15 days of pharmacological wash-out and after 15 days of treatment with Trandolapril (T, 4 mg, n=10), Verapamil (V, 240 mg, n=10), or both (T 2 mg+V 180 mg, n=10). Each experiment consisted of 4 30-min periods (baseline, MS, recovery I and II). Renal hemodynamics was evaluated with effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) from plasminogen activator inhibitor and inulin clearance, respectively. MS increased blood pressure (BP) to a similar extent before and after each treatment. Before treatment, the increasing BP was not associated with any modification of ERPF in the 3 groups. Renal vascular resistances (RVR) markedly increased during MS (+23% in the T group, +21.6% in the V group, and +32.9% in the T+V group); GFR remained constant during the whole experiment. After treatment, ERPF decreased significantly during MS in the T group (-15%, P<0.05) and in the V group (-11.7%, p<0.01); in the T+V group, ERPF modifications were not statistically significant (P=0.07). In the T group, ERPF reverted to baseline values at the end of the stimulus, whereas in the V group, renal vasoconstriction was more prolonged. Only in hypertensive patients treated with 4 mg of T, RVR reverted to baseline during the recovery I, whereas in the V group, RVR remained elevated for the whole experiment. No modifications of GFR were observed in all groups. The kidney of hypertensive patients cannot react to a sympathetic stimulus with the physiological vasoconstriction. A short-term antihypertensive treatment with 4 mg of T restores the physiological renal response to adrenergic activation.

Low diastolic ambulatory blood pressure is associated with greater all-cause mortality in older patients with hypertension.

OBJECTIVES: To assess the relationship between office and ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) and total mortality in elderly patients with hypertension. DESIGN: Observational prospective cohort study. SETTING: Hypertension outpatient clinic in a geriatric academic hospital. PATIENTS AND METHODS: Eight hundred five older (> or =60) subjects with hypertension underwent office and ambulatory BP measurement. Mortality was assessed after a mean follow-up of 3.8 years. RESULTS: In a total of 3,090 person-years of follow-up, 107 participants died (average mortality rate 3.5% per year). With bivariate analysis, participants who died had higher SBP and PP and lower DBP, with office and ambulatory measurements. Mortality rates were greater with higher SBP and lower with higher DBP. As a combined effect of these trends, PP was associated with the widest death rate gradients, from 12 to 66, 13 to 63, and 9 to 70 per 1,000 person-years across office, 24-hour, daytime, and nighttime PP quartiles, respectively. Multivariate Cox analysis confirmed these trends; the adjusted hazard of death increased linearly with increasing ambulatory SBP and PP, whereas it decreased significantly with increasing ambulatory DBP. A five times greater risk of death was detected when comparing night-time PP quartile 4 (median PP value 78 mmHg) with quartile 1 (median PP value 46 mmHg). CONCLUSION: In older patients with hypertension, low DBP and high PP, particularly when measured using ambulatory BP monitoring, are associated with greater risk of death. The achievement of an SBP treatment goal should not be obtained at the expense of an excessive DBP reduction.

Are comorbidity indices useful in predicting all-cause mortality in Type 2 diabetic patients? Comparison between Charlson index and disease count.

BACKGROUND AND AIMS: Several studies have shown that comorbidity is important in predicting morbidity and mortality in the general population. However, few studies have assessed the validity of comorbidity indices in diabetic patients. The aim of the present study was to compare the predictive value of disease count and Charlson's Comorbidity Index (CCI) for 3-year mortality in type 2 diabetic (T2D) patients. METHODS: The study was performed on a consecutive series of 1667 T2D outpatients. Comorbidity was assessed using Charlson's index, whereas the diseases used to calculate Charlson's score were taken into account for disease count. Information on all-cause mortality over the 3-year follow-up period was obtained from the City of Florence Registry Office. RESULTS: Mean duration of follow-up (+/-SD) was 31.4+/-10.6 months. One hundred and ninety-nine (11.9%) patients died during follow-up, with a yearly mortality rate of 4.7%. At multivariate analysis, after adjustment for sex and age, each additional disease was associated with a 54 [37-77]% increase in all-cause mortality. Mortality increased by 31 [21-41]% for each incremental point of Charlson's comorbidity score. CONCLUSIONS: A simple disease count is as predictive of mortality in T2D patients as the more complex Charlson's index. The possible usefulness of specific comorbidity indices in predicting incident disability in diabetic subjects needs to be further investigated.

Pulse pressure and mortality in hypertensive type 2 diabetic patients. A cohort study.

HYPOTHESIS: Hypertension is a well-known cardiovascular risk factor in type 2 diabetic patients. It has been suggested that pulse pressure (PP) could be an independent cardiovascular risk factor in the general population, particularly in the elderly. An association between office PP and cardiovascular mortality has been previously reported in diabetic patients, while the relationship between ambulatory measurements of PP and all-cause mortality has not been assessed so far. AIM: To assess the relationship between ambulatory PP and all-cause mortality in diabetic patients with hypertension. METHODS: A cohort study was performed on a consecutive series of 435 diabetic outpatients. All patients underwent office blood pressure measurement (OBP) and 24-h ambulatory blood pressure monitoring (ABPM). Mortality was assessed through queries at the Registry Offices of the city of residence for each patient. Mean follow-up was 3.8 +/- 1.2 years. RESULTS: Fifty-eight patients (13.3%) died during the follow-up. Mortality was significantly (p < 0.05) higher in patients in the highest quartile and lower in patients in the lowest quartile, when compared to the intermediate quartiles, both for office and ABPM-PP. In a multivariate analysis, after adjustment for numerous variables (including current hypoglycaemic, antihypertensive statin and aspirin treatment), mortality was increased by 3.1 and 5.3% for each incremental mmHg of office PP (p < 0.05) and ABPM-PP (p < 0.001) respectively. CONCLUSIONS: High PP, assessed through office measurement or ABPM, was associated with increased mortality in hypertensive type 2 diabetic patients. In our sample, PP assessed with ABPM is a better predictor of mortality than office PP.

Calcium channel blockers and nephroprotection.

The prevalence and incidence of End-Stage Renal Disease (ESRD) have progressively increased in the last 20 years. Hypertension and diabetes are the two most important causes of ESRD, and antihypertensive treatment plays a crucial role in preventing Chronic Renal Failure (CRF) and ESRD. The glomerulus and mesangial extracellular matrix are the principal sources giving rise to hypertensive nephropathy, which is finally characterized by progressive glomerulosclerosis. Several mechanisms are involved in hypertensive nephropathy, including increases in intraglomerular pressure and extracellular matrix production and reactive oxygen species (ROS)-related damage. The various activities of antihypertensive drugs on the kidney are particularly important in understanding their nephroprotective role and in developing new nephroprotective pathways in the future. This paper reviews the main pathophysiological aspects of renal damage in hypertension, the effects of various types of calcium channel blockers (CCBs) on renal function, and their role in nephroprotection.