Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: <=90 (n=6264); <=85 (n=6264); <=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure<=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure <=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of <=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of <=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels <=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure <=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

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; > or = 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.

A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP) levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline) to 147.3±20.1/90.8±10.9 mmHg (week 12) (p<0.05). Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35%) patients took telmisartan 40mg throughout the study and 81 (65%) had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication). CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

Exercise testing in hypertensive patients taking different angiotensin-converting enzyme inhibitors

OBJECTIVE: To compare blood pressure response to dynamic exercise in hypertensive patients taking trandolapril or captopril. METHODS: We carried out a prospective, randomized, blinded study with 40 patients with primary hypertension and no other associated disease. The patients were divided into 2 groups (n=20), paired by age, sex, race, and body mass index, and underwent 2 symptom-limited exercise tests on a treadmill before and after 30 days of treatment with captopril (75 to 150 mg/day) or trandolapril (2 to 4 mg/day). RESULTS: The groups were similar prior to treatment (p<0.05), and both drugs reduced blood pressure at rest (p<0.001). During treatment, trandolapril caused a greater increase in functional capacity (+31%) than captopril (+17%; p=0.01) did, and provided better blood pressure control during exercise, observed as a reduction in the variation of systolic blood pressure/MET (trandolapril: 10.7±1.9 mmHg/U vs 7.4±1.2 mmHg/U, p=0.02; captopril: 9.1±1.4 mmHg/U vs 11.4±2.5 mmHg/U, p=0.35), a reduction in peak diastolic blood pressure (trandolapril: 116.8±3.1 mmHg vs 108.1±2.5 mmHg, p=0.003; captopril: 118.2±3.1 mmHg vs 115.8±3.3 mmHg, p=0.35), and a reduction in the interruption of the tests due to excessive elevation in blood pressure (trandolapril: 50% vs 15%, p=0.009; captopril: 50% vs 45%, p=0.32). CONCLUSION: Monotherapy with trandolapril is more effective than that with captopril to control blood pressure during exercise in hypertensive patients.

Malignant hypertension and hypertensive encephalopathy in primary aldosteronism caused by adrenal adenoma

Two cases are reported as follows: 1) 1 female patient with accelerated-malignant hypertension secondary to an aldosterone-producing adrenal adenoma; and 2) 1 female patient with adrenal adenoma, severe hypertension, and hypertensive encephalopathy. This association is a rare clinical finding, and malignant hypertension may modify the hormonal characteristic of primary aldosteronism, making its diagnosis more difficult. The diagnosis of primary aldosteronism should be considered in patients with malignant hypertension or hypertensive encephalopathy if persistent hypokalemia occurs. Identification of primary aldosteronism is of paramount importance for the patient's evolution, because the surgical treatment makes the prognosis more favorable.

Hypertensive diabetic patients: guidelines for conduct and their difficulties

OBJECTIVE: To assess the effect of blood pressure (BP) control and other cardiovascular risk factors in patients with diabetes mellitus in a referral service for the treatment of hypertension. METHODS: A retrospective study where diabetic patients (at least 2 fasting glucose levels above 126 mg/dL, use of hypoglycemic agents or insulin, or both of these) were included. They were evaluated at the first appointment (M1) and at the last appointment (M2), regarding blood pressure, body mass index (BMI), use of hypertensive drugs, glycemia, total cholesterol (TC), creatinine, and potassium. RESULTS: Of 1,032 patients studied, 146 patients with a mean age of 61.6 years had diabetes, and 27 were men (18.5%). Mean follow-up was 5.5 years. BP values were 161.6 x 99.9 mmHg in M1 and 146.3 x 89.5 mmHg in M2. In M1, 10.4% of the patients did not use medications, 50.6% used just 1 drug, 30.8% used 2 drugs, and 8.2% used 3 or more drugs. In M2, these values were 10.9%, 39%, 39.7%, and 10.4%, respectively. Diuretics were the most commonly used medication, whereas angiotensin-converting enzyme inhibitors (ACE inhibitors) were those drugs which presented greater increase when comparing M1 to M2 (24.6% and 41.7%, respectively). Only 17,1% reached the recommended goal (BP<130x85 mmhg). The other cardiovascular risk factors did not change significantly. CONCLUSION: Our data reinforce the necessity of a more aggressive approach in the treatment of these patients, despite the social and economic difficulties in adhering to treatment.

Blood Pressure Control in Hypertensive Patients in the "Hiperdia Program": A Territory-Based Study

Background:Systemic hypertension is highly prevalent and an important risk factor for cardiovascular events. Blood pressure control in hypertensive patients enrolled in the Hiperdia Program, a program of the Single Health System for the follow-up and monitoring of hypertensive patients, is still far below the desired level.Objective:To describe the epidemiological profile and to assess blood pressure control of patients enrolled in Hiperdia, in the city of Novo Hamburgo (State of Rio Grande do Sul, Brazil).Methods:Cross-sectional study with a stratified cluster random sample, including 383 adults enrolled in the Hiperdia Program of the 15 Basic Health Units of the city of Porto Alegre, conducted between 2010 and 2011. Controlled blood pressure was defined as ≤140 mmHg × 90 mmHg. The hypertensive patients were interviewed and their blood pressure was measured using a calibrated aneroid device. Prevalence ratios (PR) with 95% confidence interval, Wald's χ2 test, and simple and multiple Poisson regression were used in the statistical analysis.Results:The mean age was 63 ± 10 years, and most of the patients were females belonging to social class C, with a low level of education, a sedentary lifestyle, and family history positive for systemic hypertension. Diabetes mellitus (DM) was observed in 31%; adherence to the antihypertensive treatment in 54.3%; and 33.7% had their blood pressure controlled. DM was strongly associated with inadequate BP control, with only 15.7% of the diabetics showing BP considered as controlled.Conclusion:Even for hypertensive patients enrolled in the Hiperdia Program, BP control is not satisfactorily reached or sustained. Diabetic hypertensive patients show the most inappropriate BP control.

Functional Vascular Study in Hypertensive Subjects with Type 2 Diabetes Using Losartan or Amlodipine

Background: Antihypertensive drugs are used to control blood pressure (BP) and reduce macro- and microvascular complications in hypertensive patients with diabetes. Objectives: The present study aimed to compare the functional vascular changes in hypertensive patients with type 2 diabetes mellitus after 6 weeks of treatment with amlodipine or losartan. Methods: Patients with a previous diagnosis of hypertension and type 2 diabetes mellitus were randomly divided into 2 groups and evaluated after 6 weeks of treatment with amlodipine (5 mg/day) or losartan (100 mg/day). Patient evaluation included BP measurement, ambulatory BP monitoring, and assessment of vascular parameters using applanation tonometry, pulse wave velocity (PWV), and flow-mediated dilation (FMD) of the brachial artery. Results: A total of 42 patients were evaluated (21 in each group), with a predominance of women (71%) in both groups. The mean age of the patients in both groups was similar (amlodipine group: 54.9 ± 4.5 years; losartan group: 54.0 ± 6.9 years), with no significant difference in the mean BP [amlodipine group: 145 ± 14 mmHg (systolic) and 84 ± 8 mmHg (diastolic); losartan group: 153 ± 19 mmHg (systolic) and 90 ± 9 mmHg (diastolic)]. The augmentation index (30% ± 9% and 36% ± 8%, p = 0.025) and augmentation pressure (16 ± 6 mmHg and 20 ± 8 mmHg, p = 0.045) were lower in the amlodipine group when compared with the losartan group. PWV and FMD were similar in both groups. Conclusions: Hypertensive patients with type 2 diabetes mellitus treated with amlodipine exhibited an improved pattern of pulse wave reflection in comparison with those treated with losartan. However, the use of losartan may be associated with independent vascular reactivity to the pressor effect.

Impact of Light Salt Substitution for Regular Salt on Blood Pressure of Hypertensive Patients

Background: Studies have shown sodium restriction to have a beneficial effect on blood pressure (BP) of hypertensive patients. Objective: To evaluate the impact of light salt substitution for regular salt on BP of hypertensive patients. Methods: Uncontrolled hypertensive patients of both sexes, 20 to 65 years-old, on stable doses of antihypertensive drugs were randomized into Intervention Group (IG - receiving light salt) and Control Group (CG - receiving regular salt). Systolic BP (SBP) and diastolic BP (DBP) were analyzed by using casual BP measurements and Home Blood Pressure Monitoring (HBPM), and sodium and potassium excretion was assessed on 24-hour urine samples. The patients received 3 g of salt for daily consumption for 4 weeks. Results: The study evaluated 35 patients (65.7% women), 19 allocated to the IG and 16 to the CG. The mean age was 55.5 ± 7.4 years. Most participants had completed the Brazilian middle school (up to the 8th grade; n = 28; 80.0%), had a family income of up to US$ 600 (n = 17; 48.6%) and practiced regular physical activity (n = 19; 54.3%). Two patients (5.7%) were smokers and 40.0% consumed alcohol regularly (n = 14). The IG showed a significant reduction in both SBP and DBP on the casual measurements and HBPM (p < 0.05) and in sodium excretion (p = 0.016). The CG showed a significant reduction only in casual SBP (p = 0.032). Conclusions: The light salt substitution for regular salt significantly reduced BP of hypertensive patients.

Protease-activated receptor (PAR)-1 and PAR-2 protect rat astrocytes from apoptotic cell death via differentially regulating JNK isoform-specific release of the chemokine GRO/CINC-1 : two novel protective pathways in brain

Protease-activated receptor; c-Jun N-terminal kinase (JNK); thrombin; neuroprotection; siRNA

Electrical Properties of Isolated Cardiomyocytes in a Rat Model of Thiamine Deficiency

In modern society, thiamine deficiency (TD) remains an important medical condition linked to altered cardiac function. There have been contradictory reports about the impact of TD on heart physiology, especially in the context of cardiac excitability. In order to address this particular question, we used a TD rat model and patch-clamp technique to investigate the electrical properties of isolated cardiomyocytes from epicardium and endocardium. Neither cell type showed substantial differences on the action potential waveform and transient outward potassium current. Based on our results we can conclude that TD does not induce major electrical remodeling in isolated cardiac myocytes in either endocardium or epicardium cells.

Progression of Blood Pressure and Cardiovascular Outcomes in Hypertensive Patients in a Reference Center

Background: Hypertension is a public health problem, considering its high prevalence, low control rate and cardiovascular complications. Objective: Evaluate the control of blood pressure (BP) and cardiovascular outcomes in patients enrolled at the Reference Center for Hypertension and Diabetes, located in a medium-sized city in the Midwest Region of Brazil. Methods: Population-based study comparing patients enrolled in the service at the time of their admission and after an average follow-up of five years. Participants were aged ≥18 years and were regularly monitored at the Center up to 6 months before data collection. We assessed demographic variables, BP, body mass index, risk factors, and cardiovascular outcomes. Results: We studied 1,298 individuals, predominantly women (60.9%), and with mean age of 56.7±13.1 years. Over time, there was a significant increase in physical inactivity, alcohol consumption, diabetes, dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed an increase in stroke and myocardial revascularization, and a lower frequency of chronic renal failure. During follow-up, there was significant improvement in the rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which were due to cardiovascular diseases. Conclusion: Despite considerable improvements in the rate of BP control during follow-up, risk factors worsened and cardiovascular outcomes increased.