Blood Pressure In Untreated Patients Research Articles

Gut microbial metabolites lower blood pressure in patients with hypertension.

Supplementation with the gut microbial-derived metabolites acetate and butyrate has been shown to lower blood pressure in experimental models of hypertension. However, the translational potential of these metabolites has been unexplored. We provide clinical evidence that acetate and butyrate lower blood pressure in untreated patients with hypertension.

LEFT VENTRICULAR GLOBAL FUNCTION INDEX AND BLOOD PRESSURE PARAMETERS IN UNTREATED PATIENTS WITH HYPERTENSION

Objective: The left ventricular global function index (LVGFI) is a novel marker that incorporates LV structure in the assessment of LV cardiac performance.Typically, LVGFI is assessed with MRI, but recently proposed a technique for calculating this index by echocardiography. It was previously shown that a decrease in LVGFI may be a predictor of adverse outcomes in young patients with hypertension and a preserved ejection fraction. The study aimed to elucidate the association between LVGFI and the features of the daily profile of blood pressure in untreated patients with essential hypertension (EH). Design and method: We included in the study 104 patients with EH (51 men (49%) and 53 women (51%)). Mean age 58,7 ± 11,73 years. All patients had no history of blood pressure-lowering treatment. All patients underwent echocardiography and ambulatory blood pressure monitoring (ABPM). LVGFI (%) was defined as left ventricular (LV) stroke volume/LV global volume∗100% where LV global volume was calculated as the sum of the LV mean cavity volume ((LV end-diastolic volume + end-systolic volume)/2) and myocardium volume (LV mass/density). End-diastolic and end-systolic volume were obtained using Teichholz method. Results: The mean LVGFI was 30,21 ± 7,32%. We performed a correlation analysis of the main clinical characteristics and parameters of ABPM with LVGFI. We found slight correlation between age (r = -0,215, p = 0,028) and body mass index (r = -0,378, p < 0,0001) with the LVGFI. There were no significant associations between office blood pressure and echocardiography parameters. Also mean daily, daytime and night systolic and diastolic blood pressure were not correlated with LVGFI. The most significant associations were found between ABPM systolic (r = -0,307, p = 0,002) and diastolic (r = -0,355, p < 0,0001) blood pressure variability. Patients with the impaired circadian rhythm of blood pressure by type of over-dipper had the lowest LVGFI (26,84 ± 3,301%) compared with patients with normal circadian rhythm (32,43 ± 6,908%) and non-dipper patients (30,49 ± 7,773%), p = 0,041. Conclusions: Lowering of LVGFI is associated with high blood pressure variability and over-dipper circadian rhythm of blood pressure.

Association Between Cardiotrophin 1 Levels and Central Blood Pressure in Untreated Patients With Essential Hypertension

Cardiotrophin 1 (CT-1) is an interleukin 6-related cytokine recently implicated in cardiac hypertrophy and vascular damage in essential hypertension (EH). We aimed first to determine CT-1 levels in naive, untreated patients with grade I EH (UH) as compared with normotensive (NT) individuals and, second, to investigate a possible association of CT-1 levels with indices of arterial stiffness. We enrolled 45 consecutive untreated patients recently diagnosed with grade I EH by means of office and ambulatory blood pressure (BP) measurements and 25 age- and sex-matched NT subjects. CT-1 levels were measured with a commercially available enzyme-linked immunosorbent assay kit, and indices of arterial stiffness were determined by applanation tonometry. CT-1 levels were significantly elevated in UH patients compared with NT subjects (P < 0.001). Furthermore, CT-1 levels correlated positively with office, ambulatory and central BP. A significant bivariable correlation was also found between CT-1 levels and pulse wave velocity (P = 0.02). In the multivariable analysis, central systolic and diastolic BP proved the only significant predictors of CT-1 levels after controlling for other related factors. To our knowledge, this is the first study that correlates CT-1 levels with ambulatory and central BP, as well as with pulse wave velocity in patients with essential hypertension. Thus, studying the effects of CT-1 in the cardiovascular system in patients with EH represents a promising area of investigation in the future.

Association of augmentation index of radial pressure wave form with diurnal variation pattern of blood pressure in untreated patients with essential hypertension

The augmentation index of the radial pulse wave has been reported to be a sensitive aortic stiffness marker in relatively young but not in older individuals. We studied the relationship between augmentation index and the diurnal blood pressure profiles. Twenty-four-hour ambulatory blood pressure monitoring was performed in 90 untreated patients with uncomplicated essential hypertension. The patients were classified into four groups: dippers, extreme dippers, nondippers, and risers. Augmentation index was calculated as the percentage of the second systolic peak relative to the first systolic peak. No significant differences in the averaged whole 24-h systolic or diastolic blood pressure were observed in the whole set of patients or in subgroup patients with age 60 years or under. In the whole set of patients (58.7 +/- 12.9 years), there were significant differences in augmentation index between patients with abnormal (other than dippers) and normal diurnal blood pressure profiles (dippers). In subgroup patients with age 60 years or below (49.1 +/- 9.1 years, n = 48), the abnormal diurnal blood pressure profile group showed significantly higher augmentation index (89.6 +/- 10.3%) than dippers (80.5 +/- 11.8%). The area under the curve in the receiver operating characteristics curve for distinguishing between dippers than other dippers was 0.73 (P < 0.01). Multivariate analysis demonstrated that abnormal diurnal blood pressure profile was independently associated with increase in augmentation index. In contrast, these relationships were not significant in the over 60 years subgroup patients (69.8 +/- 5.6 years old, n = 42). The present study revealed that augmentation index was associated with dipping blood pressure patterns in untreated hypertensive patients aged 60 years or younger. Augmentation index determination would be useful for initial assessment in connection with possible abnormal diurnal blood pressure variability in patients with age 60 years or younger.

Effects of hygienic-dietary recommendations on ambulatory blood pressure in untreated patients with grade 1 hypertension

P-20 Key Words: Mild Hypertension, Hygienic-Dietary Intervention, BP Control

Further evidence on the administration-time dependent effects of aspirin on blood pressure in untreated hypertensive patients

Recent studies have shown no influence of aspirin (ASA) on blood pressure (BP) in hypertensive patients under antihypertensive therapy, yet little if any attention has been paid so far in clinical trials to potential circadian-time dependencies in effects. However, an administration-time dependent effect of low-dose ASA on BP has been previously documented in normotensive volunteers, in patients with untreated mild hypertension, and in pregnant women at high risk for preeclampsia [Hermida et al. Hypertension. 2003;41:in press]. In keeping with these findings, the present study investigated the influence of ASA on BP in previously untreated hypertensive patients, who received ASA at different times of the day according to their rest-activity cycle. We studied 147 patients with mild hypertension (57 men and 90 women), 43.0±12.1 (mean±SD) years of age, divided in 3 groups: non-pharmacological hygienic-dietary recommendations (HDR); the same HDR and ASA (100 mg/day) on awakening; or HDR and ASA before bedtime. BP and heart rate (HR) were measured every 20 minutes during the day (07:00 to 23:00 hours) and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of BP in each group was established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204]. After 3 months of non-pharmacological intervention, there was a small and non-significant reduction of BP (1.1 and 1.0 mm Hg for systolic and diastolic BP; P>0.341). There was no effect of ASA on BP when given on awakening (P=0.229). A BP reduction was, however, highly signif-icant when ASA was given before bedtime (decrease of 7.1 and 4.4 mm Hg in systolic and diastolic BP, respectively; P<0.001). There was no significant change in HR in any group. This trial corroborates the highly significant administration-time dependent effect of low-dose ASA on BP in untreated patients with mild hypertension. Results indicate that the timed administration of low-dose ASA with respect to the rest-activity cycle of each patient could provide a valuable approach not just for the secondary prevention of cardiovascular disease, but also in the added BP control of patients with mild essential hypertension and poor compliance with hygienic and/or dietary recommendations.

Efecto de la administración temporalizada de ácido acetilsalicílico a dosis bajas sobre la presión arterial en pacientes hipertensos

Previous studies on the potential influence of aspirin (AAS) on blood pressure have not taken in consideration the chronopharmacologic effects of non-steroidal antiinflammatory drugs. This pilot study investigated the effects of AAS on blood pressure in hypertensive patients under no antihypertensive treatment who received AAS at different day times according to their rest-activity cycle. We studied 64 untreated patients with mild hypertension (24 men), 43.5 (12.0) (mean [SD]) years of age, randomly divided in 3 groups: group 1, non-pharmacological hygienic-dietetic recommendations; group 2, the same recommendations plus AAS (100 mg/day) on awakening, and group 3, the same recommendations plus AAS (100 mg/day) before bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of blood pressure in each group was established by population multiple-component analysis. Circadian parameters obtained for each group of patients before and after the intervention were compared with a nonparametric paired test. After 3 months of non-pharmacological intervention, there was a small and non-significant reduction of blood pressure (< 1.5 mmHg; p = 0.28). There was no change in blood pressure when AAS was given on awakening (p = 0.21). A highly significant blood pressure reduction was, however, observed in patients who received AAS before bedtime (decrease of 7 and 5 mmHg in systolic and diastolic blood pressure, respectively; p = 0.006). Our results indicate a statistically significant time-dependent administration effect of low-dose AAS on blood pressure in untreated patients with mild hypertension. This effect reinforces the need to quantify and control AAS effects in patients using this agent in combination with antihypertensive agents.

Administration-time dependent influence of aspirin on blood pressure in previously untreated hypertensive patients

Several studies have shown statistically significant circadian rhythms in thromboxane and prostacyclin production, circulating platelets, platelet aggregation, clotting and fibrinolytic inhibitors, circulating angiotensin II, angiotensin sensitivity, and the inhibition of platelet aggregation produced by aspirin (ASA). Moreover, ASA exhibits a faster drug-disappearance rate when administered during the morning as compared to the evening. Despite this evidence, previous studies on the potential influence of ASA on blood pressure (BP) have not taken into consideration the chronopharmacological effects of nonsteroidal antiinflammatory drugs. This pilot study investigates the effects of ASA on BP in untreated hypertensive patients who received ASA at different times of the day according to their rest-activity cycle. We studied 78 patients with mild hypertension (36 men), 43.5±11.4 (mean±SD) years of age, divided in 3 groups: non-pharmacological hygienic-dietary recommendations (HDR); HDR and ASA (100 mg/day) on awakening; or HDR and ASA before bedtime. BP and heart rate (HR) were measured every 20 minutes during the day (07:00 to 23:00 hours) and every 30 minutes at night for 48 consecutive hours before and after 3 months of intervention. The circadian pattern of BP in each group was established by population multiple-component analysis [Fernandez & Hermida. Chronobiol Int. 1998;15:191-204]. After 3 months of non-pharmacological intervention, there was a small and non-significant reduction of BP (1.2 mm Hg for systolic BP, 1.4 mm Hg for diastolic BP; P=0.264). There was no effect of ASA on BP when given on awakening (P=0.211). A BP reduction was, however, highly significant when ASA was given before bedtime (decrease of 7.6 and 6.1 mm Hg in systolic and diastolic BP, respectively; P<0.001). There was no significant change in HR in any group. Results indicate a statistically significant administration-time dependent effect of low-dose ASA on BP in untreated patients with mild hypertension. In any trial of ASA effects, inquiries about the time when subjects took the drug are indicated and may account for discrepancies in the literature. Moreover, the influence of ASA on BP demonstrated here indicates the need to identify and control for ASA effects in patients using this drug before or during their participation in antihypertension medication trials. DGES, PM98-0106; PGICT00-PXI-32205PN; University of Vigo.

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials

Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 x 2 contingency tables after application of Zelen's test of heterogeneity. In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% CI 2-22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37). Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

Importance of Weight Loss and Sodium Restriction in the Treatment of Mild and Moderate Essential Hypertension

The effectiveness of non pharmacological treatment of chronic arterial hypertension has been evaluated in 116 treated or not primary hypertensive out-patients. Those receiving diuretics were however excluded. This population was requested to follow for 3 months a modification of their usual diet characterized by salt restriction combined with energy intake restriction when the patients were above their ideal body weight. Only 62 patients (53%) completed the study. However, this approach was effective by decreasing blood pressure and total cholesterol. The weight loss appears the most effective way to decrease blood pressure in untreated patients, but needs 3 months to be significant. In drug-treated patients, the sodium restriction significantly influences the blood pressure level, already after 1 month. However, salt sensitivity has been noted, especially in the most severe forms of the hypertensive disease. The combination of both modifications (weight loss and sodium restriction) does not appear to be more effective than each separate dietary measure.

Relation of blood pressure with body and plasma electrolytes in Conn's syndrome.

Thirty-four patients with untreated Conn's syndrome were studied in a metabolic ward. The final diagnosis in each case was based on the finding and removal of an adrenal cortical adenoma with histological features typical of the disorder. Compared with 34 age and sex-matched normal controls the untreated patients had increased plasma aldosterone concentration, increased blood pressure (183/112 mmHg), increased exchangeable sodium (116.7% of normal), hypokalaemia and increased plasma sodium concentration. Exchangeable potassium was lower than normal and plasma concentrations of active renin, total renin and angiotensin II were lower than normal mean values. Arterial pressure correlated significantly and positively with plasma and exchangeable sodium and there was a significant negative correlation with plasma potassium concentration. Partial regression analysis showed that the relation of exchangeable sodium with blood pressure did not depend on age or renal function but that the relation of blood pressure and plasma potassium could be attributed to the correlation of exchangeable sodium and blood pressure. Multiple regression analysis suggested that exchangeable and plasma sodium were the most important determinants of blood pressure in untreated patients. Spironolactone, amiloride and surgical removal of the adenoma corrected the electrolyte abnormality and usually lowered blood pressure. The fall in exchangeable sodium was related to the fall in blood pressure. The pattern of correlation found by multiple regression analysis in postoperative patients was similar to that in normal subjects. The findings are relevant to some of the mechanisms proposed for the hypertension of mineralocorticoid excess.

Effects of Indomethacin Alone and during Diuretic or β-Adrenoreceptor-Blockade Therapy on Blood Pressure and the Renin System in Essential Hypertension

1. Indomethacin was administered alone or in addition to either diuretic or propranolol therapy to three groups of patients with essential hypertension on a free sodium diet. 2. Indomethacin administration reduced renin secretion by about 30% in untreated uncomplicated hypertensive patients and by about 75% in those whose renin secretion had either been stimulated or suppressed by maintained diuretic or beta-adrenoreceptor-blockade therapy. 3. Indomethacin administration produced no net effect on blood pressure in untreated patients with uncomplicated hypertension but it blunted or reversed the antihypertensive effect of either diuretic or propranolol therapy. 4. Salt and water retention may be an important factor in the blood pressure-raising effect of indomethacin during diuretic or propranolol therapy: In addition, prostaglandin synthesis may be important in counteracting increased alpha-adrenergic tone, which may limit the blood pressure-lowering effect of beta-adrenoreceptor-blockade. 5. Because of these interactions and their pressor potential indomethacin should be used with caution when combined with either diuretics or beta-adrenoreceptor blockers.