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Concept: Blood pressure

441

Two decades of research indicate causal associations between social relationships and mortality, but important questions remain as to how social relationships affect health, when effects emerge, and how long they last. Drawing on data from four nationally representative longitudinal samples of the US population, we implemented an innovative life course design to assess the prospective association of both structural and functional dimensions of social relationships (social integration, social support, and social strain) with objectively measured biomarkers of physical health (C-reactive protein, systolic and diastolic blood pressure, waist circumference, and body mass index) within each life stage, including adolescence and young, middle, and late adulthood, and compare such associations across life stages. We found that a higher degree of social integration was associated with lower risk of physiological dysregulation in a dose-response manner in both early and later life. Conversely, lack of social connections was associated with vastly elevated risk in specific life stages. For example, social isolation increased the risk of inflammation by the same magnitude as physical inactivity in adolescence, and the effect of social isolation on hypertension exceeded that of clinical risk factors such as diabetes in old age. Analyses of multiple dimensions of social relationships within multiple samples across the life course produced consistent and robust associations with health. Physiological impacts of structural and functional dimensions of social relationships emerge uniquely in adolescence and midlife and persist into old age.

Concepts: Epidemiology, Hypertension, Obesity, Blood pressure, Sociology, Body mass index, Old age, Vector space

344

Background The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. Methods We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. Results At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. Conclusions Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062 .).

Concepts: Blood, Myocardial infarction, Atherosclerosis, Hypertension, Stroke, Blood pressure, Artery, Orthostatic hypotension

262

Regular exercise training improves maximal oxygen uptake (VO2max), but the optimal intensity and volume necessary to obtain maximal benefit remains to be defined. A growing body of evidence suggests that exercise training with low-volume but high-intensity may be a time-efficient means to achieve health benefits. In the present study, we measured changes in VO2max and traditional cardiovascular risk factors after a 10 wk. training protocol that involved three weekly high-intensity interval sessions. One group followed a protocol which consisted of 4×4 min at 90% of maximal heart rate (HRmax) interspersed with 3 min active recovery at 70% HRmax (4-AIT), the other group performed a single bout protocol that consisted of 1×4 min at 90% HRmax (1-AIT). Twenty-six inactive but otherwise healthy overweight men (BMI: 25-30, age: 35-45 y) were randomized to either 1-AIT (n = 11) or 4-AIT (n = 13). After training, VO2max increased by 10% (∼5.0 mL⋅kg(-1)⋅min(-1)) and 13% (∼6.5 mL⋅kg(-1)⋅min(-1)) after 1-AIT and 4-AIT, respectively (group difference, p = 0.08). Oxygen cost during running at a sub-maximal workload was reduced by 14% and 13% after 1-AIT and 4-AIT, respectively. Systolic blood pressure decreased by 7.1 and 2.6 mmHg after 1-AIT and 4-AIT respectively, while diastolic pressure decreased by 7.7 and 6.1 mmHg (group difference, p = 0.84). Both groups had a similar ∼5% decrease in fasting glucose. Body fat, total cholesterol, LDL-cholesterol, and ox-LDL cholesterol only were significantly reduced after 4-AIT. Our data suggest that a single bout of AIT performed three times per week may be a time-efficient strategy to improve VO2max and reduce blood pressure and fasting glucose in previously inactive but otherwise healthy middle-aged individuals. The 1-AIT type of exercise training may be readily implemented as part of activities of daily living and could easily be translated into programs designed to improve public health.

Concepts: Blood, Myocardial infarction, Atherosclerosis, Blood pressure, Artery, Pulse, Cardiac cycle, Systole

246

Background Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. Methods We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician's choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups. Results Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P=0.06). The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P=0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively. Conclusions In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure. (Funded by the National Health and Medical Research Council of Australia; INTERACT2 ClinicalTrials.gov number, NCT00716079 .).

Concepts: Hypertension, Blood pressure, Modified Rankin Scale, Cerebral hemorrhage, Disability, Orthostatic hypotension, Barthel scale, Rehabilitation medicine

198

Slow deep breathing improves blood oxygenation (Sp(O2)) and affects hemodynamics in hypoxic patients. We investigated the ventilatory and hemodynamic effects of slow deep breathing in normal subjects at high altitude. We collected data in healthy lowlanders staying either at 4559 m for 2-3 days (Study A; N = 39) or at 5400 m for 12-16 days (Study B; N = 28). Study variables, including Sp(O2) and systemic and pulmonary arterial pressure, were assessed before, during and after 15 minutes of breathing at 6 breaths/min. At the end of slow breathing, an increase in Sp(O2) (Study A: from 80.2±7.7% to 89.5±8.2%; Study B: from 81.0±4.2% to 88.6±4.5; both p<0.001) and significant reductions in systemic and pulmonary arterial pressure occurred. This was associated with increased tidal volume and no changes in minute ventilation or pulmonary CO diffusion. Slow deep breathing improves ventilation efficiency for oxygen as shown by blood oxygenation increase, and it reduces systemic and pulmonary blood pressure at high altitude but does not change pulmonary gas diffusion.

Concepts: Oxygen, Blood, Heart, Respiratory physiology, Blood pressure, Artery, Vein, Pulse oximetry

184

BACKGROUND: To evaluate the effect of lifestyle modifications on metabolic syndrome (MetS) as assessed by its resolution and improved values for its components. METHODS: This was a systematic review and meta-analysis. Searches were performed of MEDLINE and the Cochrane Database from January 1966 to October 2011 to identify randomized controlled trials (RCTs) related to the study objective. The included studies were RCTs restricted to the English language, with a follow-up period of 6 months or more, which reported overall resolution of MetS or values of MetS components (fasting blood glucose, waist circumference, high-density lipoprotein (HDL), triglycerides, and systolic and diastolic blood pressure (SBP, DBP)) . Two investigators independently assessed study eligibility. The effect sizes were the relative proportion of patients with resolved MetS and mean differences in MetS component values from baseline to 1-year follow-up in a lifestyle-modification intervention (LMI) group versus a control (conventional lifestyle education or no treatment) group. Meta-analyses were conducted using a random-effects model. RESULTS: Eleven interventions in eight RCTs were used for the meta-analyses. The relative proportion of patients with resolved MetS in the intervention group was approximately 2.0 (95% CI 1.5 to 2.7) times greater in the intervention group compared with the control group (7 interventions, n = 2.839). LMI (5 interventions, n = 748) significantly reduced mean values for SBP by 6.4 mmHg (95% CI 9.7 to 3.2), DBP by 3.3 mmHg (95% CI 5.2 to 1.4), triglycerides by 12.0 mg/dl ( 95% CI 22.2 to 1.7), waist circumference by 2.7 cm (95% CI 4.6 to 0.9), and fasting blood glucose by 11.5 mg/dl (95% CI 22.4 to 0.6) (5 interventions), but reductions were not significant for HDL (1.3 mg/dl; 95% CI 0.6 to 3.1). CONCLUSIONS: The LMI was effective in resolving MetS and reducing the severity of related abnormalities (fasting blood glucose, waist circumference, SBP and DBP, and triglycerides) in subjects with MetS.

Concepts: Atherosclerosis, Evidence-based medicine, Systematic review, Randomized controlled trial, Blood pressure, Blood sugar, Effect size, Meta-analysis

181

Hypertension is the most common condition seen in primary care and leads to myocardial infarction, stroke, renal failure, and death if not detected early and treated appropriately. Patients want to be assured that blood pressure (BP) treatment will reduce their disease burden, while clinicians want guidance on hypertension management using the best scientific evidence. This report takes a rigorous, evidence-based approach to recommend treatment thresholds, goals, and medications in the management of hypertension in adults. Evidence was drawn from randomized controlled trials, which represent the gold standard for determining efficacy and effectiveness. Evidence quality and recommendations were graded based on their effect on important outcomes. There is strong evidence to support treating hypertensive persons aged 60 years or older to a BP goal of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg; however, there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal, or in those younger than 30 years for a diastolic goal, so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion. The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease (CKD) as for the general hypertensive population younger than 60 years. There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, calcium channel blocker, or thiazide-type diuretic in the nonblack hypertensive population, including those with diabetes. In the black hypertensive population, including those with diabetes, a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy. There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes. Although this guideline provides evidence-based recommendations for the management of high BP and should meet the clinical needs of most patients, these recommendations are not a substitute for clinical judgment, and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient.

Concepts: Chronic kidney disease, Myocardial infarction, Hypertension, Stroke, Blood pressure, Renin-angiotensin system, Angiotensin II receptor antagonist, ACE inhibitor

173

Blunted nighttime blood pressure dipping is an established cardiovascular risk factor. This study examined the effect of job strain on nighttime blood pressure dipping among men and women with high blood pressure.

Concepts: Blood, Myocardial infarction, Atherosclerosis, Hypertension, Blood vessel, Cardiovascular disease, Blood pressure, Orthostatic hypotension

173

To examine whether there is a difference in the association between high pulse pressure and proteinuria, independent of other blood pressure (BP) indices, such as systolic or diastolic BP, among subjects with diabetes, prediabetes, or normal glucose tolerance.

Concepts: Nutrition, Insulin, Cardiology, Blood pressure, Glucose tolerance test, The Association, Ventricle, Pulse pressure

172

The kidney functions in key physiological processes to filter blood and regulate blood pressure via key molecular transporters and ion channels. Sex-specific differences have been observed in renal disease incidence and progression, as well as acute kidney injury in response to certain drugs. Although advances have been made in characterizing the molecular components involved in various kidney functions, the molecular mechanisms responsible for sex differences are not well understood. We hypothesized that the basal expression levels of genes involved in various kidney functions throughout the life cycle will influence sex-specific susceptibilities to adverse renal events.

Concepts: DNA, Renal failure, Kidney, Gene, Genetics, Gene expression, Blood pressure, Renin