Prediction of sustained antihypertensive efficacy of chronic captopril therapy: relationships to immediate blood pressure response and control plasma renin activity

The blood pressure (BP) lowering effect of the orally active angiotensin converting enzyme inhibitor, captopril (SQ14225), was studied in 59 hypertensive patients maintained on a constant sodium intake. Within 2 hours of the first dose of captopril BP fell from 171/107 to a maximum low of 142/92 mm Hg (p less than 0.001), and after 4 to 8 days to treatment BP averaged 145/94 mm Hg (p less than 0.001). The magnitude of BP drop induced by captopril was significantly correlated to baseline plasma renin activity (PRA) both during the acute phase (r = -0.38, p less than 0.01) and after the 4 to 8-day interval (r = -0.33, p less than 0.01). Because of considerable scatter in individual data, renin profiling was not precisely predictive of the immediate or delayed BP response of separate patients. However, the BP levels achieved following the initial dose of captopril were closely correlated to BP measured after 4 to 8 days of therapy, and appeared to have greater predictive value than control PRA of the long-term efficacy of chronic captopril therapy despite marked BP changes occurring in some patients during the intermediate period. Because of these intermediate BP changes, addition of a diuretic to enhance antihypertensive effectiveness of angiotensin blockade should be restrained for several days after initiation of captopril therapy.

Blood pressure loci identified with a gene-centric array.

Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56 × 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56 × 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.

Blood pressure in relation to coffee and caffeine consumption.

The relationship between blood pressure (BP) and coffee is of major interest given its widespread consumption and the public health burden of high BP. Yet, there is no specific recommendation regarding coffee intake in existing hypertension guidelines. The lack of a definitive understanding of the BP-coffee relationship is partially attributable to issues that we discuss in this review, issues such as acute vs. chronic effects, genetic and smoking effect modifications, and coffee vs. caffeine effects. We also present evidence from meta-analyses of studies on the association of BP with coffee intake. The scope of this review is limited to the latest advances published with a specific focus on caffeine, acknowledging that caffeine is only one among numerous components in coffee that may influence BP. Finally, considering the state of the research, we propose a mechanism by which the CYP1A2 gene and enzyme influence BP via inhibition of the adenosine receptor differentially in smokers and non-smokers.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons.

OBJECTIVE: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and has been shown to be feasible in elderly persons. Wrist manometers have recently been proposed for such home BP measurement, but their accuracy has not been previously assessed in elderly patients. METHODS: Forty-eight participants (33 women and 15 men, mean age 81.3±8.0 years) had their BP measured with a wrist device with position sensor and an arm device in random order in a sitting position. RESULTS: Average BP measurements were consistently lower with the wrist than arm device for systolic BP (120.1±2.2 vs. 130.5±2.2 mmHg, P<0.001, means±SD) and diastolic BP (66.0±1.3 vs. 69.7±1.3 mmHg, P<0.001). Moreover, a 10 mmHg or greater difference between the arm and wrist device was observed in 54.2 and 18.8% of systolic and diastolic measures, respectively. CONCLUSION: Compared with the arm device, the wrist device with position sensor systematically underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant and questions the use of the wrist device to monitor BP in elderly persons. This study points to the need to validate BP measuring devices in all age groups, including in elderly persons.

Genetic dissection of sodium and potassium transport along the aldosterone-sensitive distal nephron: Importance in the control of blood pressure and hypertension.

In this review, we discuss genetic evidence supporting Guyton's hypothesis stating that blood pressure control is critically depending on fluid handling by the kidney. The review is focused on the genetic dissection of sodium and potassium transport in the distal nephron and the collecting duct that are the most important sites for the control of sodium and potassium balance by aldosterone and angiotensin II. Thanks to the study of Mendelian forms of hypertension and their corresponding transgenic mouse models, three main classes of diuretic receptors (furosemide, thiazide, amiloride) and the main components of the aldosterone- and angiotensin-dependent signaling pathways were molecularly identified over the past 20years. This will allow to design rational strategies for the treatment of hypertension and for the development of the next generation of diuretics.

Modelling the cardiovascular system for automatic interpretation of the blood pressure curve

A four compartment model of the cardiovascular system is developed. To allow for easy interpretation and to minimise the number of parameters, an effort was made to keep the model as simple as possible. A sensitivity analysis is first carried out to determine which are the most important model parameters to characterise the blood pressure signal. A four stage process is then described which accurately determines all parameter values. This process is applied to data from three patients and good agreement is shown in all cases.

Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles.

OBJECTIVE: An inverse relationship between blood pressure (BP) and cognitive function has been found in adults, but limited data are available in adolescents and young adults. We examined the prospective relation between BP and cognitive function in adolescence. METHODS: We examined the association between BP measured at the ages of 12-15 years in school surveys and cognitive endpoints measured in the Seychelles Child Development Study at ages 17 (n = 407) and 19 (n = 429) years, respectively. We evaluated multiple domains of cognition based on subtests of the Cambridge Neurological Test Automated Battery (CANTAB), the Woodcock Johnson Test of Scholastic Achievement (WJTA), the Finger Tapping test (FT) and the Kaufman Brief Intelligence Test (K-BIT). We used age, sex and height-specific z-scores of SBP, DBP and mean arterial pressure (MAP). RESULTS: Six out of the 21 cognitive endpoints tested were associated with BP. However, none of these associations were found to hold for both males and females or for different subtests within the same neurodevelopmental domain or for both SBP and DBP. Most of these associations disappeared when analyses were adjusted for selected potential confounding factors such as socio-economic status, birth weight, gestational age, BMI, alcohol consumption, blood glucose, and total n-3 and n-6 polyunsaturated fats. CONCLUSIONS: Our findings do not support a consistent association between BP and subsequent performance on tests assessing various cognitive domains in adolescents.

Fitness, sport et pression artérielle [Fitness, sports and blood pressure].

Blood pressure is lowered for a few hours after aerobic exercise, but also after resistance exercise, although for a shorter period of time. An exercise program can significantly lower resting and ambulatory BP measurements. Multiple mechanisms interact for the BP lowering effect, such as decreased total peripheral resistance, enhanced endothelial function, diminished sympathetic or rennin plasmatic activity, structural vascular modifications and baroreceptor reflex modulation. New exercises like eccentric or isometric (handgrip) contractions are promising. Resistance activities have long been considered dangerous for blood vessels because of increased arterial stiffness, but if the intensity remains moderate and aerobic exercises are integrated, then the effects are altogether beneficial.

Blood pressure changes in acute ischemic stroke and outcome with respect to stroke etiology.

OBJECTIVE: Previous research suggested that proper blood pressure (BP) management in acute stroke may need to take into account the underlying etiology. METHODS: All patients with acute ischemic stroke registered in the ASTRAL registry between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin Scale score >2. A local polynomial surface algorithm was used to assess the effect of baseline and 24- to 48-hour systolic BP (SBP) and mean arterial pressure (MAP) on outcome in patients with lacunar, atherosclerotic, and cardioembolic stroke. RESULTS: A total of 791 patients were included in the analysis. For lacunar and atherosclerotic strokes, there was no difference in the predicted probability of unfavorable outcome between patients with an admission BP of <140 mm Hg, 140-160 mm Hg, or >160 mm Hg (15.3 vs 12.1% vs 20.8%, respectively, for lacunar, p = 015; 41.0% vs 41.5% vs 45.5%, respectively, for atherosclerotic, p = 075), or between patients with BP increase vs decrease at 24-48 hours (18.7% vs 18.0%, respectively, for lacunar, p = 0.84; 43.4% vs 43.6%, respectively, for atherosclerotic, p = 0.88). For cardioembolic strokes, increase of BP at 24-48 hours was associated with higher probability of unfavorable outcome compared to BP reduction (53.4% vs 42.2%, respectively, p = 0.037). Also, the predicted probability of unfavorable outcome was significantly different between patients with an admission BP of <140 mm Hg, 140-160 mm Hg, and >160 mm Hg (34.8% vs 42.3% vs 52.4%, respectively, p < 0.01). CONCLUSIONS: This study provides evidence to support that BP management in acute stroke may have to be tailored with respect to the underlying etiopathogenetic mechanism.

Assessing heterogeneity of effects on blood pressure in a meta-analysis of pharmacist interventions trials

Background: Recent reviews of randomized control trials have shown that pharmacist interventions improve cardiovascular diseases (CVD) risk factors in outpatients. Various interventions were evaluated in different settings, and a substantial heterogeneity was observed in the effect estimates. To better express uncertainties in the effect estimates, prediction intervals (PI) have been proposed but are, however, rarely reported. Objective: Pooling data from two systematic reviews, we estimated the effect of pharmacist interventions on systolic blood pressure (BP), computed PI, and evaluated potential causes of heterogeneity. Methods: Data were pooled from systematic reviews assessing the effect of pharmacist interventions on CVD risk factors in patients with or without diabetes, respectively. Effects were estimated using random effect models. Results: Systolic BP was the outcome in 31 trials including 12 373 patients. Pharmacist interventions included patient educational interventions, patient-reminder systems, measurement of BP, medication management and feedback to physician, or educational intervention to health care professionals. Pharmacist interventions were associated with a large reduction in systolic BP (-7.5 mmHg; 95% CI: -9.0 to -5.9). There was a substantial heterogeneity (I2: 66%). The 95% PI ranged from -13.9 to -1.0 mmHg. The effect tended to be larger if the intervention was conducted in a community pharmacy and if the pharmacist intervened at least monthly. Conclusion: On average, the effect of pharmacist interventions on BP was substantial. However, the wide PI suggests that the effect differed between interventions, with some having modest effects and others very large effects on BP. Part of the heterogeneity could be due to differences in the setting and in the frequency of the interventions.

Physical activity is inversely associated with high blood pressure independently of overweight in Brazilian adolescents.

The purpose of this study was to assess the relationship between blood pressure (BP) levels and physical activity (PA) domains accounting for overweight/obesity. Adolescents aged 10 to 17 years old were recruited (n = 1021). International Obesity Task Force (IOTF) criteria were used to define overweight and obesity. High BP was defined using the Center of Disease Control and Prevention criteria. Different domains of PA (school activities, sport out of school, and leisure time PA) were assessed using a validated questionnaire. The prevalence of overweight/obesity was 21.9% for boys and 14.8% for girls. Some 13.4% of boys and 10.2% of girls, respectively, had high blood pressure (HBP). A strong and positive association was found between overweight and HBP. After adjustment for body mass index (BMI), total PA was inversely associated with BP. When all PA domains were entered simultaneously in a regression model, and after adjustment for BMI, only sport out of school was significantly and inversely associated with systolic BP [β: -0.82 (-1.50; -0.13)]. These findings open avenue for the early prevention of HBP by the prevention of obesity and promotion of PA.