BP-lowering Drugs Research Articles

Noninvasive evaluation of varying pulse pressures in vivo using brachial sphymomanometry, applanation tonometry, and Pulse Wave Ultrasound Manometry

The routine assessment and monitoring of hypertension may benefit from the evaluation of arterial pulse pressure (PP) at more central locations (e.g. the aorta) rather solely at the brachial artery. Pulse Wave Ultrasound Manometry (PWUM) was previously developed by our group to provide direct, noninvasive aortic PP measurements using ultrasound elasticity imaging. Using PWUM, radial applanation tonometry, and brachial sphygmomanometry, this study investigated the feasibility of noninvasively obtaining direct PP measurements at multiple arterial locations in normotensive, pre-hypertensive, and hypertensive human subjects. Two-way ANOVA indicated a significantly higher aortic PP in the hypertensive subjects, while radial and brachial PP were not significantly different among the subject groups. No strong correlation (r2 < 0.45) was observed between aortic and radial/brachial PP in normal and pre-hypertensive subjects, suggesting that increases in PP throughout the arterial tree may not be uniform in relatively compliant arteries. However, there was a relatively strong positive correlation between aortic PP and both radial and brachial PP in hypertensive subjects (r2 = 0.68 and 0.87, respectively). PWUM provides a low-cost, non-invasive, and direct means of measuring the pulse pressure in large central arteries such as the aorta. When used in conjunction with peripheral measurement devices, PWUM allows for the routine screening of hypertension and monitoring of BP-lowering drugs based on the PP from multiple arterial sites.

Effects of blood-pressure-lowering treatment in hypertension: 9. Discontinuations for adverse events attributed to different classes of antihypertensive drugs: meta-analyses of randomized trials.

Choice of antihypertensive drugs is also based on the expected burden of adverse events associated with each class of agents, and we have recently identified treatment discontinuation for adverse events as a measure of treatment tolerability frequently reported in randomized controlled trials (RCTs). To investigate whether all classes of blood pressure (BP) lowering drugs increase discontinuations for adverse events when compared with placebo and whether risk of discontinuation is similar for all classes when compared in head-to-head RCTs. RCTs of BP-lowering treatment were subdivided in groups according to class of drug compared with placebo or with other classes. Risk ratios and 95% confidence intervals of major cardiovascular events and of treatment discontinuations for adverse events were calculated (random-effects model). Thirty-eight placebo-controlled RCTs (147 788 patients) and 37 head-to-head RCTs (242 481 patients) provided comparative information on discontinuations for adverse events. All classes of drugs significantly increased discontinuations for adverse events over those occurring on placebo: risk ratio diuretics 2.23 (1.32-3.76), beta-blockers 2.88 (1.58-5.28), calcium antagonists 2.03 (1.17-3.56), angiotensin-converting enzyme inhibitors 2.78 (1.37-5.47), central agents 1.74 (1.24-2.45), with the single exception of angiotensin receptor blockers, which did not significantly increase adverse events over placebo [risk ratio 1.13 (0.78-1.62)]. Similarly, in head-to-head comparison RCTs with other classes, angiotensin receptor blockers were the only class associated with a significantly lower risk of adverse events [risk ratio 0.71 (0.58-0.87)] when head-to-head compared with other classes. Regression analysis also shows that incidence of discontinuations for adverse events is proportional to the number of antihypertensive and other cardiovascular drugs, which accounts for the high incidence of this outcome often found in groups randomized to placebo. Reduction of cardiovascular events by all classes of BP-lowering drugs is accompanied by increased treatment discontinuations for adverse events, except when angiotensin receptor blockers are used. Treatment discontinuations are also related to treatment often accompanying antihypertensive agents.

PP.26.02] FREE VERSUS FIXED COMBINATION ANTIHYPERTENSIVE THERAPY FOR ESSENTIAL ARTERIAL HYPERTENSION

Objective: Most patients with arterial hypertension (HTN) require more than one blood pressure (BP)-lowering drug to achieve BP target. In a free drug combination, each BP-lowering drug is administered as a separate pill, while in a fixed drug combination, BP-lowering drugs are combined in a single pill. The objective of this systematic review is to compare the beneficial and harmful effects of using a fixed versus free combination of BP-lowering agents in patients with essential HTN. Design and method: We conducted a comprehensive search that included the Cochrane CENTRAL, MEDLINE, and EMBASE. We included randomized clinical trials (RCTs) addressing the objective of the review and assessing at least one of the following outcomes: BP-lowering efficacy, rapidity in achieving BP target, compliance, incidence of side effects, mortality, and morbidity outcomes. Two review authors independently and in duplicate selected eligible studies then abstracted relevant information and assessed risk of bias using standardized data extraction forms. The primary meta-analyses used a random-effects model. Results: We identified seven eligible RCTs with a total of 397 participants. Meta-analysis for the pre-specified outcome of efficacy in controlling BP showed a non-significant reduction of mean systolic BP of 0.81 mmHg (95% CI -3.25, 1.64) favoring the fixed combination group. As for the outcome of adverse events, meta-analysis results showed a non-significant 13% risk reduction favoring the free combination group (risk ratio 1.13, 95% CI 0.85, 1.5). Quality of evidence was low for both outcomes. Rapidity in achieving BP target was assessed in one trial, and the results favored the fixed combination group. Adherence to treatment was assessed in three trials, no pooled analysis was possible due to either missing data or differences in the methods of outcome measurement. The included trials were short term, none assessed mortality and morbidity.Conclusions: The available low quality evidence does not confirm or rule out a substantive difference in benefits or harms between fixed combination and free combination of anti-hypertensive regimen in the management of patients with HTN. Well designed RCTs with a long duration of follow-up and assessment of morbidity and mortality outcomes are needed.

PP.22.03] 24-HOUR URINE ALPHA-1-MICROGLOBULIN AS A MARKER OF HYPERTENSION-INDUCED RENAL IMPAIRMENT AND ITS RESPONSE ON DIFFERENT BP-LOWERING DRUGS.

Objective: The purpose of this study was to assess the role of urine α1-microglobulin as a marker of hypertension-induced renal damage compared to the gold-standard markers (estimated glomerular filtration rate, eGFR; urine albumin and urine albumin-to-creatinine ratio, ACR). Its response on different BP-lowering drugs was also studied. Design and method: Sixty never-treated hypertensives (65.0% males, 46.9 years, 141.4/94.0 mmHg) were randomized to an angiotensin receptor blocker (ARB)- or non-dihydropyridine calcium channel blocker (CCB)-based regimen. Patients with diabetes, established cardiovascular or renal disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical blood pressure (BP) normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and α1-microglobulin were measured and ACR was calculated. Results: Minor changes (p = NS) in eGFR were noted during follow-up in both groups (from 111.0 to 108.4 and from 111.3 to 114.0 ml/min/1.73 m2 in the ARB and CCB group, respectively). 24-hour urine indices were all significantly improved (P < 0.01) with ARB (albumin from 19.4 to 8.2 mg/l, ACR from 21.5 to 10.0 mg/g, α1-microglobulin from 5.06 to 3.64 mg/l) but not (P = NS) with CCB treatment (albumin from 15.6 to 13.9 mg/l, ACR from 17.6 to 17.1 mg/g, α1-microglobulin from 4.94 to 4.79 mg/l). These differences between groups remained significant (P < 0.05) after adjusting for office heart rate (HR) and BP. Alpha-1-microglobulin was significantly correlated (P < 0.05) to albumin and ACR both at baseline (r = 0.283 and 0.299, respectively) and at the end of follow-up (r = 0.432 and 0.465, respectively) but not (P = NS) to eGFR. It was also significantly related (P < 0.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r = 0.264 and 0.436, respectively) and at the end of follow-up (r = 0.308 and 0.472, respectively). Conclusions: Urine α1-microglobulin emerges as a potentially valuable marker of hypertension-induced renal impairment. Its kinetics and its response to treatment appears similar to that of albumin. ARBs emerge as superior to non-dihydropyridine CCBs at improving its excretion in urine, independently of HR/BP control.

OP.4C.08] ROLE OF THE FIXED-DOSE TRIPLE COMBINATION THERAPY IN THE MANAGEMENT OF UNCONTROLLED HYPERTENSION

Objective: Blood pressure (BP) control is difficult to achieve with current BP-lowering drugs. Therefore, uncontrolled hypertension (HT) despite drug treatment with free recommended combinations remains the main goal in clinical practice. In this study the efficacy of a triple fixed-combination (TFC) of anti-hypertensive drugs in hypertensive subjects with uncontrolled HT was evaluated.Design and method: Forty-one hypertensives (mean age 59.2 ± 12.7 years, 63.4% males) with uncontrolled essential HT (clinic systolic BP > = 140 or diastolic BP > = 90 mmHg) previously treated with anti-hypertensive therapy with a renin-angiotensin-aldosterone system (RAAS) inhibitor (ramipril 5 to 10 mg or olmesartan 10 to 40 mg daily) plus hydrochlorothiazide (12.5 to 25 mg daily) were switched to once daily TFC therapy with perindopril (5 to 10 mg), indapamide (1.25 to 2.5 mg) and amlodipine (5 to 10 mg). These subjects were age-sex- matched with hypertensive patients taking a free-combination therapy including a RAAS inhibitor, a diuretic and a calcium channel blocker (CCB). Clinic BP and ambulatory BP (ABPM) were evaluated at baseline and after 1-month follow-up. Analysis of variance for repeated measures was provided. Results: In both treatment groups, a significant reduction of all the components of clinic and ABPM values was found (data not shown) at the end of follow-up. When ABPM values were considered, at the follow-up a significant reduction of the 24 h, daytime and night-time systolic and pulse pressure was found in the TFC group than in the free combination therapy group (Figure). Diastolic BP and heart rate remained unchanged. No patients were lost at the follow-up and no side effects were observed. Conclusions: A TFC of perindopril, amlodipine and indapamide appears to be safe, well tolerated and effective in reducing systolic and pulse pressure in hypertensive patients uncontrolled by a free antihypertensive therapy including a RAAS inhibitor, a diuretic and a CCB.

Antihypertensive Drug Use, Blood Pressure Variability, and Incident Stroke Risk in Older Adults: Three-City Cohort Study.

The aim was to determine the association between antihypertensive drug class and incident stroke controlling for long-term blood pressure (BP) variability (BPV) in people aged ≥65 years. The sample included 5951 participants (median age 74 years, 60% women) taking at least 1 drug for hypertension (3727/5951) or with systolic BP >140 mm Hg or diastolic BP >90 mm Hg. Participants were evaluated for incident fatal and nonfatal stroke to 12 years follow-up. BPV was calculated with the coefficient of variation method and regressed against 9 antihypertensive drug classes (BPVreg). Hazard models were used to determine hazard ratios for incident stroke risk attributable to drug class, adjusted for BP, BPVreg, covariates, and delayed entry bias. There were 273 incident strokes over a median of 9.1 years (interquartile range 6.4-10.4). Stroke risk was generally not reduced by BP-lowering drugs. Angiotensin receptor blockers (hazard ratio 1.56; 95% confidence interval 1.06-2.28; P=0.02) and β-blockers (hazard ratio 1.41; 95% confidence interval 1.03-1.92; P=0.03) were associated with an increased total stroke risk. Angiotensin receptor blockers and β-blockers were also associated with ischemic strokes after adjustment for systolic BPV. Diastolic BPV was associated with stroke risk in analyses stratified by systolic BP 140 to 160 mm Hg (per 0.10 increase in coefficient of variation, hazard ratio 1.59; 95% confidence interval 1.05-2.40; P=0.03). The angiotensin receptor blocker and β-blocker drug classes were associated with incident stroke and ischemic stroke in older adults. BPV was generally not associated with incident stroke.

High Risk versus Proportional Benefit: Modelling Equitable Strategies in Cardiovascular Prevention

ObjectiveTo examine the performances of an alternative strategy to decide initiating BP-lowering drugs called Proportional Benefit (PB). It selects candidates addressing the inequity induced by the high-risk approach since it distributes the gains proportionally to the burden of disease by genders and ages.Study Design and SettingMild hypertensives from a Realistic Virtual Population by genders and 10-year age classes (range 35–64 years) received simulated treatment over 10 years according to the PB strategy or the 2007 ESH/ESC guidelines (ESH/ESC). Primary outcomes were the relative life-year gain (life-years gained-to-years of potential life lost ratio) and the number needed to treat to gain a life-year. A sensitivity analysis was performed to assess the impact of changes introduced by the ESH/ESC guidelines appeared in 2013 on these outcomes.ResultsThe 2007 ESH/ESC relative life-year gains by ages were 2%; 10%; 14% in men, and 0%; 2%; 11% in women, this gradient being abolished by the PB (relative gain in all categories = 10%), while preserving the same overall gain in life-years. The redistribution of benefits improved the profile of residual events in younger individuals compared to the 2007 ESH/ESC guidelines. The PB strategy was more efficient (NNT = 131) than the 2013 ESH/ESC guidelines, whatever the level of evidence of the scenario adopted (NNT = 139 and NNT = 179 with the evidence-based scenario and the opinion-based scenario, respectively), although the 2007 ESH/ESC guidelines remained the most efficient strategy (NNT = 114).ConclusionThe Proportional Benefit strategy provides the first response ever proposed against the inequity of resource use when treating highest risk people. It occupies an intermediate position with regards to the efficiency expected from the application of historical and current ESH/ESC hypertension guidelines. Our approach allows adapting recommendations to the risk and resources of a particular country.

Television viewing duration and blood pressure among 18-74-year-old adults. The French nutrition and health survey (ENNS, 2006-2007).

To describe Blood Pressure (BP) according to the time spent viewing television and examine whether the associations between television viewing and systolic and diastolic BP differed depending on sex, age and BMI. The French health and nutrition survey (ENNS) was conducted in 2006-2007 on a multistage stratified random sample of 18-74-year-old adults. Systolic (SBP) and diastolic BP (DBP) were assessed using three measurements. Among subjects without BP-lowering drugs and lifestyle measures, adjusted means of SBP and DBP were estimated for each television viewing category (<3h and ≥3h). Among 2050 ENNS participants, 81.2% declared neither drug medication nor lifestyle change to lower BP. In women without BP-lowering measure, viewing television 3h/day or more increased significantly SBP and DBP adjusted means (+2mmHg) compared to women who spent less than 3h/day in front of the television. These associations were stronger in obese or 35-54-year-old women. In men, no relationship between DBP and television-viewing has been observed. Though, SBP was positively associated with television-viewing in non-overweight, 18-29 or 55-74 year-old men. These results show that the association between television viewing duration and BP must be evaluated differently between gender, age group and BMI category.

Prevention And Treatment of Hypertension With Algorithm-based therapy (PATHWAY) number 2: protocol for a randomised crossover trial to determine optimal treatment for drug-resistant hypertension

IntroductionResistant hypertension is inadequately controlled blood pressure (BP) despite treatment with at least three BP-lowering drugs. A popular hypothesis is that resistant hypertension is due to excessive Na+-retention, and that...

Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics

BackgroundCholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels. MethodsA total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization. ResultsParticipants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women. ConclusionsThe HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.govNCT00468923).

ACP Journal Club. Review: In patients with mild hypertension and no CV disease, BP-lowering drugs reduce stroke and mortality.

Source Citation Sundstrom J, Arima H, Jackson R, et al; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of blood pressure reduction in mild hypertension: a systematic review and...

Associations of central and brachial blood pressure with cognitive function: a population-based study.

Previous observational studies on the association between brachial blood pressure (BP) and cognition have reported conflicting results. Central BP has been hypothesized to be more strongly related to cognition than brachial BP. The aim of this study was to assess the association between brachial as well as central BP and cognitive function, both cross-sectionally and with brachial BP measured 17 years before cognitive testing. The study population comprised 2548 individuals aged 61-85 years at follow-up (61.4% women). The cognitive tests administered were A Quick Test of cognitive speed and the Mini Mental State Examination. In fully adjusted linear regressions, small but significant cross-sectional associations were found between higher BP (systolic, diastolic and pulse pressure) and worse results on both of the cognitive tests (P-values <0.05). No significant prospective associations were found. Central BP did not show a stronger association than brachial BP did. After stratification, significant results were mainly found in the group taking BP-lowering drugs at follow-up. In summary, these findings add to existing evidence on the relationship between BP and cognition, but they do not support a superior role of central compared with brachial BP in the elderly.

Achievement of therapeutic targets in patients with diabetes and chronic kidney disease: insights from the Associazione Medici Diabetologi Annals initiative.

Chronic kidney disease (CKD) entails a worse cardiovascular outcome. The aim of our work was to study the relationship between CKD and the achievement of recommended targets for glycated haemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) in a real-life sample of patients with type 2 diabetes mellitus (T2DM). We analysed a sample of 116 777 outpatients from the Network of the Italian Association of Clinical Diabetologists; all patients had T2DM and at least one measurement of HbA1c, LDL-c, BP, serum creatinine and albuminuria in the year 2010. The outcome was the achievement of HbA1c, LDL-c and BP values as recommended by International Guidelines. In the entire sample, the mean value of HbA1c was 7.2 ± 1.2%, of LDL-c was 102 ± 33 mg/dL and of BP was 138/78 ± 19/9 mmHg. CKD and its components were associated with poor glycaemic and BP control, notwithstanding greater use of glucose and BP-lowering drugs, while no association was found with LDL-c values. Factors independently related to unsatisfactory glycaemic control included female gender, body mass index, duration of disease and high albuminuria. Men, older people and those taking statins were more likely to reach LDL-c target levels. Male gender, age and high albuminuria strongly affected the achievement of BP targets. CKD or its components, mainly high albuminuria, are associated with failure to reach therapeutic targets, especially for HbA1c and BP, despite a greater use of drugs in patients with T2DM.

Randomized controlled trials of blood pressure lowering in hypertension: a critical reappraisal.

Sixty-eight blood pressure (BP)-lowering randomized controlled trials (defined as randomized controlled trials comparing active treatment with placebo, or less active treatment, achieving a BP difference, performed between 1966 and end 2013 in cohorts with ≥ 40% hypertensive patients, and exclusive of trials in acute myocardial infarction, heart failure, acute stroke, and dialysis) were identified and meta-analyzed grouping the randomized controlled trials on the basis of clinically relevant questions: (1) does BP lowering reduce all types of cardiovascular outcome? (2) Is prevention of all outcomes proportional to the extent of systolic, diastolic, and pulse BP? (3) Have all classes of BP-lowering drugs been shown capable of reducing all types of cardiovascular outcome? (4) Is BP lowering beneficial when intervention is initiated at any grade (or stage) of hypertension? (5) Do BP-lowering randomized controlled trials provide evidence about systolic BP and diastolic BP targets of treatment? (6) Should BP-lowering treatment be preferentially addressed to patients in higher risk categories promising larger absolute treatment benefits? The results of these meta-analyses provide further support to current hypertension treatment guidelines by showing that BP lowering can significantly reduce major cardiovascular outcomes largely independent of the agents used, significant risk reduction is found at all hypertension grades (stages), and when systolic BP is lowered below a cut off of 140 mm Hg with some further reduction limited to stroke at systolic BP values just <130 mm Hg. Absolute risk reduction progressively increases higher is total cardiovascular risk, but this greater benefit is associated with a progressively higher residual risk, ie, higher treatment failures.

A hipertensão arterial e o exercício físico: elementos para uma prescrição médica

Physical activity is associated with health benefits including a reduction in blood pressure (BP). A recent meta-analysis shows that exercise may reduce BP to a degree comparable to first-line BP-lowering drugs. It was originally thought that the BP-lowering effect of exercise was limited to endurance exercise and that resistance or isometric exercise was harmful. Recent evidence contests this idea. The evidence is scarce but suggests a role for exercise in the primary prevention of hypertensive disease. The favourable influence of exercise on important risk factors such as hypertriglyceridemia and overweight has already been demonstrated. Exercise is important in the primary and secondary prevention of hypertension. For most patients, the benefits of exercise largely exceed the risks. For individuals at risk, medical evaluation is indicated in order to allow safe and patient-oriented prescription of exercise.

Pooled RCTs: BP-lowering drugs reduced major CV events; absolute reductions were greater with higher baseline risk.

Source Citation The Blood Pressure Lowering Treatment Trialists' Collaboration, Sundström J, Arima H, et al. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet. 2014;384:591-8. 25131978

Effects of blood pressure lowering on outcome incidence in hypertension. 1. Overview, meta-analyses, and meta-regression analyses of randomized trials.

Antihypertensive treatment is based on randomized controlled trials (RCTs) started since 1966. Meta-analyses comprehensive of all RCTs but limited to RCTs investigating blood pressure (BP) lowering in hypertensive patients are lacking. Two clinical questions were investigated: the extent of different outcome reductions by BP lowering in hypertensive patients, and the proportionality of outcome reductions to SBP, DBP, and pulse pressure (PP) reductions. PubMed between 1966 and December 2013 (any language), Cochrane Collaboration Library and previous overviews were used as data sources for identifying and selecting all RCTs comparing the antihypertensive drugs with placebo or less intense BP lowering (intentional BP-lowering RCTs); comparing BP-lowering drugs with placebo without BP-lowering intention, but with BP difference (nonintentional BP-lowering RCTs); and enrolling at least 40% hypertensive patients. RCTs on acute myocardial infarction, heart failure, acute stroke, and dialysis were excluded. RCT quality was assessed by scoring. Risk ratios and 95% confidence interval (CI), standardized to 10/5 mmHg SBP/DBP reduction, of seven fatal and nonfatal outcomes were calculated (random-effects model). The relationships of different outcome reductions to SBP, DBP, and PP reductions were investigated by meta-regressions. A total of 68 RCTs (245,885 individuals) were eligible, of which 47 (153,825 individuals) were 'intentional' RCTs. All outcomes were reduced (P < 0.001) by BP lowering, stroke [-36% (-29, -42)], and heart failure [-43% (-28, -54)] to a greater extent, with smaller reductions for coronary events [coronary heart disease (CHD): -16% (-10, -21)], cardiovascular [-18% (-11, -24)], and all-cause mortality [-11% (-5, -16)]. Absolute risk reductions were 17 (14, 20) strokes, 28 (19, 35) cardiovascular events, and 8 (4, 12) deaths prevented every 1000 patients treated for 5 years. Logarithmic risk ratios were related to SBP, DBP, and PP reductions (P = 0.001-0.003) for stroke and composite cardiovascular events, but not for CHD. Meta-analyses of all BP-lowering RCTs involving hypertensive patients provide precise estimates of benefits (larger for stroke and heart failure, but also significant for CHD and mortality). Absolute risk reductions are substantial. Relationships of logarithmic risk ratios with BP reductions imply risk reduction increases progressively to a smaller extent the larger the BP reduction.

Blood Pressure, Gait Speed, and Mortality in Very Old Individuals: A Population-Based Cohort Study

ObjectivesClinical trials and observational studies have produced contradictory results regarding the association of blood pressure (BP) and mortality in people aged 80 years or older. Gait speed at usual pace has been shown to moderate this association in a population of noninstitutionalized people aged 65 years or older. The aims of this study were to investigate the association of BP with all-cause mortality in a representative sample of people aged 85 years or older and to assess whether gait speed moderates this association. Design, Setting, and ParticipantsA total of 806 participants in the population-based prospective Umeå 85+/GERDA study aged 85, 90, and 95 years or older. MeasurementsGait speed at usual pace was measured over 2.4 m. The main outcome was hazard ratios (HRs) for all-cause mortality according to systolic and diastolic BP categories in the total sample and in faster-walking (≥0.5 m/s, n = 312) and slower-walking (<0.5 m/s, n = 433) subcohorts; the latter also included habitually nonwalking participants. Comprehensive adjustments were made for sociodemographic and clinical characteristics associated with death. ResultsMean age and baseline systolic and diastolic BP were 89.6 ± 4.6 years, 146.8 ± 23.9 mm Hg, and 74.8 ± 11.1 mm Hg, respectively. Most (n = 561 [69%]) participants were women, 315 (39%) were care facility residents, and 566 (70%) were prescribed BP-lowering drugs. Within 5 years, 490 (61%) participants died. In the total sample and slower-walking subcohort, systolic BP appeared to be inversely associated with mortality, although not independent of adjustments. Among faster-walking participants, mortality risk after adjustment was more than 2 times higher in those with systolic BP of 140 to 149 mm Hg (HR = 2.25, 95% confidence interval [CI] = 1.03–4.94) and 165 mm Hg or higher (HR = 2.13, 95% CI = 1.01–4.49), compared with systolic BP of 126 to 139 mm Hg. Mortality risk was also independently higher in faster-walking participants with diastolic BP higher than 80 mm Hg, compared with diastolic BP of 75 to 80 mm Hg (HR = 1.76, 95% CI = 1.07–2.90). ConclusionThe gait speed threshold of 0.5 m/s may be clinically useful for the distinction of very old people with and without increased all-cause mortality risk due to elevated systolic and diastolic BP.

Abstract 438: Association between Insomnia and Use of BP-lowering Drugs in hypertensive Patients: a Cross-sectional Cohort Study

Purpose: Insomnia and short sleep duration have been associated with increased prevalence, incidence and severity of hypertension. However, the relationship between insomnia and use of different antihypertensive drug classes has not been ascertained yet. Methods: 371 hypertensive patients at their first visit in a tertiary Hypertension Outpatient Unit were enrolled. Insomnia Severity Index (ISI), Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAY-Y2) were administered. Insomnia was defined as ISI&gt;8, depressive symptoms as BDI&gt;10, trait anxiety as STAI -Y2&gt;40. Patients with self-reported sleep apneas or snoring (n=29) or with incomplete data (n=12) were excluded. Results: Data from 330 patients were analyzed (males 51%, mean age 57±13 years, antihypertensive treatment 84%, previous CV events 9%, diabetes 7%, obesity 24%, smoking 13%, hypercholesterolemia 67%). Insomniacs (n=70, 21%) were older than non-insomniacs (60±11 vs 56±13 years, p=0.02); female gender (62 vs 46%, p=0.01), anxiety (68 vs 34%, p&lt;0.0001) and depressive symptoms (30 vs 6%, p&lt;0.0001) were more prevalent in insomniacs. Insomniacs were treated with higher number of antihypertensive drugs (1.8±1.0 vs 1.5±1.0, p=0.04) and more frequently with angiotensin-receptor-blockers (ARBs, 49 vs 31%, p=0.009) and diuretics (50 vs 28%, p=0.0007), whereas the use of other drug classes was similar. In a multiple logistic regression analysis, adjusted for cardiovascular and psychiatric variables, ARBs use (OR 2.4, CL95% 1.1-5.2), depressive symptoms (OR 3.2, CL95%1.2-8.7) and anxiety (OR 2.9, CL95%1.4-6.1) were associated with a higher probability of insomnia. Conclusions: This cross-sectional analysis suggests that ARBs use may be associated with insomnia in a cohort of hypertensive patients

The effect of attenuating age‐related increases in blood pressure in male and female spontaneously hypertensive rats on the kidney (1136.17)

The kidney is critical in the long‐term control of blood pressure, and renal inflammation has been linked to the progression of hypertension. Previous experiments have shown a sex difference in protein excretion and the renal immune cell profile: male SHRs have greater indices of renal injury and more pro‐hypertensive renal T helper17 cells (Th17) while females had more BP‐lowering T regulatory cells (Tregs). Male and female SHR were randomized to receive tap water (vehicle) or the BP‐lowering drugs, hydrochlorothiazide and reserpine, in drinking water from 5 to 12 weeks of age. BP was measured by tail cuff, and kidneys were isolated for flow cytometric analysis of T cells. Treatment attenuated age‐related increases in BP in males (174±4 vs. 137±4 mmHg, p&lt;0.05) and females (132±4 vs 161±1 mmHg, p&lt;0.05). However, treatment did not significantly change metabolic parameters, urinary electrolyte excretion (Na+, K+, Cl‐) or urinary protein excretion in either sex. In contrast, although attenuation of the development of hypertension did not significantly change the renal T cell profile in male SHR, females exhibited a decrease in renal Tregs (p=0.0091) and Th17 (p=0.0203) counts which abolished the sex differences observed in the renal T cell profile of vehicle‐treated rats.