Showing papers by "Suzanne Oparil published in 2016"

Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥75 Years: A Randomized Clinical Trial.

Abstract: Importance The appropriate treatment target for systolic blood pressure (SBP) in older patients with hypertension remains uncertain. Objective To evaluate the effects of intensive ( Design, Setting, and Participants A multicenter, randomized clinical trial of patients aged 75 years or older who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Recruitment began on October 20, 2010, and follow-up ended on August 20, 2015. Interventions Participants were randomized to an SBP target of less than 120 mm Hg (intensive treatment group, n = 1317) or an SBP target of less than 140 mm Hg (standard treatment group, n = 1319). Main Outcomes and Measures The primary cardiovascular disease outcome was a composite of nonfatal myocardial infarction, acute coronary syndrome not resulting in a myocardial infarction, nonfatal stroke, nonfatal acute decompensated heart failure, and death from cardiovascular causes. All-cause mortality was a secondary outcome. Results Among 2636 participants (mean age, 79.9 years; 37.9% women), 2510 (95.2%) provided complete follow-up data. At a median follow-up of 3.14 years, there was a significantly lower rate of the primary composite outcome (102 events in the intensive treatment group vs 148 events in the standard treatment group; hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]) and all-cause mortality (73 deaths vs 107 deaths, respectively; HR, 0.67 [95% CI, 0.49-0.91]). The overall rate of serious adverse events was not different between treatment groups (48.4% in the intensive treatment group vs 48.3% in the standard treatment group; HR, 0.99 [95% CI, 0.89-1.11]). Absolute rates of hypotension were 2.4% in the intensive treatment group vs 1.4% in the standard treatment group (HR, 1.71 [95% CI, 0.97-3.09]), 3.0% vs 2.4%, respectively, for syncope (HR, 1.23 [95% CI, 0.76-2.00]), 4.0% vs 2.7% for electrolyte abnormalities (HR, 1.51 [95% CI, 0.99-2.33]), 5.5% vs 4.0% for acute kidney injury (HR, 1.41 [95% CI, 0.98-2.04]), and 4.9% vs 5.5% for injurious falls (HR, 0.91 [95% CI, 0.65-1.29]). Conclusions and Relevance Among ambulatory adults aged 75 years or older, treating to an SBP target of less than 120 mm Hg compared with an SBP target of less than 140 mm Hg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and death from any cause. Trial Registration clinicaltrials.gov Identifier:NCT01206062

SPRINT Trial Results: Latest News in Hypertension Management

Abstract: We thank the editors of Hypertension for the invitation to discuss aspects of the recently published Systolic Blood Pressure Intervention Trial (SPRINT; ClinicalTrials.gov identifier NCT01206062) main results.1 This commentary focuses on generalizability of the findings and what is known about serious adverse effects that may be related to the SPRINT intervention. SPRINT compared the effects of antihypertensive treatment with a systolic blood pressure (SBP) target of <120 mm Hg (intensive treatment) versus <140 mm Hg (standard treatment) in 9361 hypertensive adults ≥50 years of age who had an average SBP of 130–180 mm Hg (the acceptable upper limit decreasing as the number of pretrial antihypertensive medications increased) and were at additional risk for cardiovascular disease (CVD).2 SPRINT was designed to recruit study participants with an average CVD risk of ≈2% per year, equivalent to a Framingham 10-year CVD risk score of 20%. The main finding in SPRINT was that a primary composite outcome of myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute decompensated heart failure, and CVD death was reduced by ≈25% in the intensive treatment group compared with the standard treatment group. Similarly, all-cause mortality was reduced by ≈27% in the intensive treatment group. During follow-up, the mean SBP was 121.5 mm Hg in the intensive treatment group and 134.6 mm Hg in the standard treatment group.1 Although many classes of medications were available, emphasis was placed on using classes with the best outcomes in large clinical trials: thiazide-type diuretics, calcium channels blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Other agents, including spironolactone, amiloride, β-blockers, vasodilators, or α-receptor blockers, could be added if necessary. The mean numbers of antihypertensive medications were 2.8 and 1.8 in the intensive treatment and standard treatment groups, respectively. On balance, the intensive intervention was well tolerated. The trial …

The Association Between Antihypertensive Medication Nonadherence and Visit-to-Visit Variability of Blood Pressure: Findings From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Abstract: Low adherence to antihypertensive medication has been hypothesized to increase visit-to-visit variability (VVV) of blood pressure (BP). We assessed the association between antihypertensive medication adherence and VVV of BP in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). VVV of BP was calculated using SD independent of mean, SD, and average real variability across study visits conducted 6 to 28 months after randomization. Participants who reported taking P

Impact of Renal Denervation on Patients With Obstructive Sleep Apnea and Resistant Hypertension – Insights From the SYMPLICITY HTN-3 Trial –

Abstract: Background Obstructive sleep apnea (OSA) is associated with activation of the sympathetic nervous system, and patients with this condition often experience elevated blood pressure (BP), increased BP variability, and nocturnal BP surges. Methods and results The SYMPLICITY HTN-3 trial was a large prospective, randomized, blinded, sham-controlled trial of renal denervation for treatment of uncontrolled, apparently treatment-resistant hypertension. In a post hoc analysis, we examined the effect of renal denervation vs. sham control on office and ambulatory (including nocturnal) systolic BP in patients with and without OSA. 26% (94/364) of renal denervation subjects and 32% (54/171) of sham control subjects had OSA. Baseline office and nighttime systolic BP values were similar in both arms, including in subjects with and without OSA. Compared with sham control, renal denervation reduced the 6-month office systolic BP in subjects with (-17.0±22.4 vs. -6.3±26.1 mmHg, P=0.01) but not in subjects without OSA (-14.7±24.5 vs. -13.4±26.4 mmHg, P=0.64), P=0.07 for the interaction between treatment arm and OSA status. In those with sleep apnea, renal denervation was also associated with a reduction in maximum (-4.8±21.8 vs. 4.5±24.6 mmHg, P=0.03) and average peak (-5.6±20.4 vs. 3.2±22.4 mmHg, P=0.02) nighttime systolic BP. Conclusions OSA subjects appeared to be responsive to renal denervation therapy. However, this hypothesis requires prospective testing. (Circ J 2016; 80: 1404-1412).

Orthostatic changes in systolic blood pressure among SPRINT participants at baseline

Abstract: Orthostatic changes in systolic blood pressure (SBP) impact cardiovascular outcomes. In this study, we aimed to determine the pattern of orthostatic systolic pressure changes in participants enrolled in the SBP Intervention Trial (SPRINT) at their baseline visit before randomization and sought to understand clinical factors predictive of these changes. Of the 9323 participants enrolled in SPRINT, 8662 had complete data for these analyses. The SBP after 1 minute of standing was subtracted from the mean value of the three preceding seated SBP values. At the baseline visit, medical history, medications, anthropometric measures, and standard laboratory testing were undertaken. The mean age of SPRINT participants was 68 years, two-thirds were male, with 30% black, 11% Hispanic, and 55% Caucasian. The spectrum of SBP changes on standing demonstrated that increases in SBP were as common as declines, and about 5% of participants had an increase, and 5% had a decrease of >20 mm Hg in SBP upon standing. Female sex, taller height, more advanced kidney disease, current smoking, and several drug classes were associated with larger declines in BP upon standing, while black race, higher blood levels of glucose and sodium, and heavier weight were associated with more positive values of the change in BP upon standing. Our cross-sectional results show a significant spectrum of orthostatic SBP changes, reflecting known (eg, age) and less well-known (eg, kidney function) relationships that may be important considerations in determining the optimal target blood pressure in long-term outcomes of older hypertensive patients.

Prevalence of pseudoresistant hypertension due to inaccurate blood pressure measurement.

Abstract: The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. Triage BP measurements and measurements obtained at the same clinic visit by trained physicians were compared in consecutive adult patients referred for uncontrolled resistant HTN (RHTN). Triage BP measurements were taken by the clinic staff during normal intake procedures. BP measurements were obtained by trained physicians using the BpTRU (VSM Med Tech Ltd. Coquitlam, Canada) device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Of 130 patients with uncontrolled RHTN, 33.1% (n = 43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (inter-quartile range) of differences in systolic BP between pseudoresistant and true resistant groups were 23 (17-33) mm Hg and 13 (6-21) mm Hg, respectively (P = .0001). The median (inter-quartile range) of differences in diastolic BP between the two groups were 12 (7-18) mm Hg and 8 (4-11) mm Hg, respectively (P = .001). Triage BP technique overestimated the prevalence of uncontrolled RHTN in approximately 33% of the patients emphasizing the importance of obtaining accurate BP measurements.

Refractory Hypertension: A Novel Phenotype of Antihypertensive Treatment Failure

Abstract: The term resistant hypertension has been used since the early 1960s to identify patients with difficult-to-treat hypertension, meaning mostly, resistance to pharmacological therapy.1 In the 5 decades since the term was seemingly first applied, resistant hypertension has been consistently defined as failure to control high blood pressure despite of use of ≥3 antihypertensive agents of different classes, including a diuretic.2–5 The 2008 American Heart Association Scientific Statement on resistant hypertension included in its definition patients whose blood pressure had been uncontrolled with 3 medications, but controlled with ≥4 medications.4 Although the number of medications required to satisfy the definition is arbitrary, the purpose of creating a category of resistant hypertension is to identify patients who, because of the difficulty in controlling their blood pressure, may benefit from special diagnostic and therapeutic considerations, including referral to a hypertension specialist. Having an agreed on definition that can be reliably applied to different cohorts has also facilitated research for this subgroup of patients, including identification of risk factors and underlying mechanisms, assessing outcomes and developing targeted treatments. The term refractory hypertension has often been used interchangeably with resistant hypertension to also refer to patients with difficult-to-treat hypertension.1–3,5 However, based on the number of respective PubMed citations resistant hypertension has been used much more often than refractory hypertension to indicate patients with hypertension resistant to pharmacological treatment. Recently, the term refractory hypertension has been applied to a small group of patients who are truly refractory to treatment, that is, patients who fail to achieve target blood pressure on maximal antihypertensive therapy.6 Determining whether such patients simply represent extreme cases of resistant hypertension or a novel phenotype in terms of risk and cause has been the focus of initial attempts to define and characterize …

Visit-to-Visit Variability of BP and CKD Outcomes: Results from the ALLHAT

Abstract: Background and objectives Increased visit-to-visit variability of BP is associated with cardiovascular disease risk. We examined the association of visit-to-visit variability of BP with renal outcomes among 21,245 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Design, setting, participants, & measurements We measured mean BP and visit-to-visit variability of BP, defined as SD, across five to seven visits occurring 6–28 months after participants were randomized to chlorthalidone, amlodipine, or lisinopril. The composite outcome included incident ESRD after assessment of SD of systolic BP or ≥50% decline in eGFR between 24 months and 48 or 72 months after randomization. We repeated the analyses using average real variability and peak value of systolic BP and for visit-to-visit variability of diastolic BP. Results Over a mean follow-up of 3.5 years, 297 outcomes occurred. After multivariable adjustment, including baseline eGFR and mean systolic BP, the hazard ratios for the composite end point were 1.29 (95% confidence interval [95% CI], 0.75 to 2.22), 1.76 (95% CI, 1.06 to 2.91), 1.46 (95% CI, 0.88 to 2.45), and 2.05 (95% CI, 1.25 to 3.36) for the second through fifth (SD of systolic BP =6.63–8.82, 8.83–11.14, 11.15–14.56, and >14.56 mmHg, respectively) versus the first (SD of systolic BP P trend =0.004). The association was similar when ESRD and a 50% decline in eGFR were analyzed separately, for other measures of visit-to-visit variability of systolic BP, and for visit-to-visit variability of diastolic BP. Conclusions Higher visit-to-visit variability of BP is associated with higher risk of renal outcomes independent of mean BP.

Body Mass Index Predicts 24-Hour Urinary Aldosterone Levels in Patients With Resistant Hypertension

Abstract: Prospective studies indicate that hyperaldosteronism is found in 20% of patients with resistant hypertension. A small number of observational studies in normotensive and hypertensive patients suggest a correlation between aldosterone levels and obesity while others could not confirm these findings. The correlation between aldosterone levels and body mass index (BMI) in patients with resistant hypertension has not been previously investigated. Our objective was to determine whether BMI is positively correlated with plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, and 24-hour urinary aldosterone in black and white patients. We performed a cross-sectional analysis of a large diverse cohort (n=2170) with resistant hypertension. The relationship between plasma aldosterone concentration, plasma renin activity, aldosterone:renin ratio, 24-hour urinary aldosterone, and BMI was investigated for the entire cohort, by sex and race (65.3% white, 40.3% men). We demonstrate that plasma aldosterone concentration and aldosterone:renin ratio were significantly correlated to BMI (P<0.0001) across the first 3 quartiles, but not from the 3rd to 4th quartile of BMI. Plasma renin activity was not correlated with BMI. Twenty-four-hour urinary aldosterone was positively correlated across all quartiles of BMI for the cohort (P<0.0001) and when analyzed by sex (men P<0.0001; women P=0.0013) and race (P<0.05), and stronger for men compared with women (r=0.19, P<0.001 versus r=0.05, P=0.431, P=0.028) regardless of race. In both black and white patients, aldosterone levels were positively correlated to increasing BMI, with the correlation being more pronounced in black and white men. These findings suggest that obesity, particularly the abdominal obesity typical of men, contributes to excess aldosterone in patients with resistant hypertension.

The J-curve phenomenon revisited again: SPRINT outcomes favor target systolic blood pressure below 120 mmHg.

Abstract: SVERRE E. KJELDSEN, SUZANNE OPARIL, KRZYSZTOF NARKIEWICZ & THOMAS HEDNER Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway, Vascular Biology and Hypertension Program, University of Alabama, Birmingham, AL, USA, Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland, and Department of Medicine, University of Göteborg, Sahlgrenska Academy, Göteborg, Sweden

Should Patients With Cardiovascular Risk Factors Receive Intensive Treatment of Hypertension to <120/80 mm Hg Target? A Protagonist View From the SPRINT Trial (Systolic Blood Pressure Intervention Trial).

Abstract: Opposing Viewpoint, see p 1311 On the basis of the main results of the SPRINT (Systolic Blood Pressure Intervention Trial), we strongly believe that older hypertensive patients at high cardiovascular risk should receive intensive treatment to a target systolic blood pressure (SBP) of <120 mm Hg.1,2 SPRINT tested the hypothesis that intensive treatment of SBP to a target of <120 mm Hg would reduce clinical events more than standard treatment to a target of <140 mm Hg. SPRINT enrolled persons ≥50 years of age with an SBP from 130 to 180 mm Hg (treated or untreated) and at high cardiovascular risk. In particular, SPRINT overenrolled high-risk subgroups, including those ≥75 years of age (SPRINT-Senior), blacks, and those with chronic kidney disease or cardiovascular disease. The mean 10-year Framingham cardiovascular disease risk score for all participants was 20%. SBP fell rapidly in the intensive-treatment group (target SBP <120 mm Hg), reaching a level ≈15 mm Hg lower than in the standard group at 1 year (121.4 vs 136.7 mm Hg) with administration of an average of 1 more antihypertensive medication. The SPRINT intervention was stopped early (median 3.26 years of follow-up) because of a 25% reduction in the primary composite end point (myocardial infarction, non–myocardial infarction acute coronary syndrome, stroke, acute decompensated heart failure, and cardiovascular death) and a 27% reduction in all-cause mortality in the intensive-treatment group. The effects of the intensive intervention on the primary outcome and all-cause mortality were consistent across all prespecified subgroups (presence or absence of previous cardiovascular disease or chronic kidney disease, male or female sex, black or nonblack race, ≥75 or <75 years of age, and baseline SBP tertile). The benefits of intensive treatment were numerically greater (34% reduction in the primary outcome and 33% reduction in all-cause …

Ambulatory Blood Pressure Monitoring in Individuals with HIV: A Systematic Review and Meta-Analysis.

Abstract: Introduction Abnormal diurnal blood pressure (BP) rhythms may contribute to the high cardiovascular disease risk in HIV-positive (HIV+) individuals. To synthesize the current literature on ambulatory BP monitoring (ABPM) in HIV+ individuals, a systematic literature review and meta-analysis were performed. Methods Medical databases were searched through November 11, 2015 for studies that reported ABPM results in HIV+ individuals. Data were extracted by 2 reviewers and pooled differences between HIV+ and HIV-negative (HIV-) individuals in clinic BP and ABPM measures were calculated using random-effects inverse variance weighted models. Results Of 597 abstracts reviewed, 8 studies with HIV+ cohorts met the inclusion criteria. The 420 HIV+ and 714 HIV- individuals in 7 studies with HIV- comparison groups were pooled for analyses. The pooled absolute nocturnal systolic and diastolic BP declines were 3.16% (95% confidence interval [CI]: 1.13%, 5.20%) and 2.92% (95% CI: 1.64%, 4.19%) less, respectively, in HIV+ versus HIV- individuals. The pooled odds ratio for non-dipping systolic BP (nocturnal systolic BP decline <10%) in HIV+ versus HIV- individuals was 2.72 (95% CI: 1.92, 3.85). Differences in mean clinic, 24-hour, daytime, or nighttime BP were not statistically significant. I2 and heterogeneity chi-squared statistics indicated the presence of high heterogeneity for all outcomes except percent DBP dipping and non-dipping SBP pattern. Conclusions An abnormal diurnal BP pattern may be more common among HIV+ versus HIV- individuals. However, results were heterogeneous for most BP measures, suggesting more research in this area is needed.

Patterns and Correlates of Baseline Thiazide-Type Diuretic Prescription in the Systolic Blood Pressure Intervention Trial

Abstract: Thiazides and thiazide-type diuretics are recommended as first-line agents for the treatment of hypertension, but contemporary information on their use in clinical practice is lacking. We examined patterns and correlates of thiazide prescription in a cross-sectional analysis of baseline data from participants enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT). We examined baseline prescription of thiazides in 7582 participants receiving at least 1 antihypertensive medication by subgroup, and used log-binomial regression to calculate adjusted prevalence ratios for thiazide prescription (versus no thiazide). Forty-three percent of all participants were prescribed a thiazide at baseline, but among participants prescribed a single agent, the proportion was only 16%. The prevalence of thiazide prescription differed significantly by demographic factors, with younger participants, women, and blacks all having higher adjusted prevalence of thiazide prescription than other corresponding subgroups. Participants in the lowest category of kidney function (estimated glomerular filtration rate <30 mL/min per 1.73 m2) were half as likely to be prescribed a thiazide as participants with preserved kidney function. In conclusion, among persons with hypertension and heightened cardiovascular risk, we found that thiazide prescription varied significantly by demographics and kidney disease status, despite limited evidence about relative differences in effectiveness.

Urinary sodium excretion predicts blood pressure response to spironolactone in patients with resistant hypertension independent of aldosterone status.

Abstract: Objective:Resistant hypertension (RHTN), blood pressure (BP) at least 140/90 mmHg despite using at least three different medications, including a diuretic, is associated with high dietary sodium and hyperaldosteronism. Mineralocorticoid receptor antagonists are recommended for treatment of RHTN, how

Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat

Abstract: Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 × 10(6) HiPS-ECs, 1.5 × 10(6) HiPS-Null-ECs, or 1.5 × 10(6) HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury.

Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Abstract: Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to −27 μV, analysis of variance P = .8612; 4 years = +10 to −17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH.

BP Targets in Hypertension: What Should We Do Now That SPRINT Is Out?

Abstract: Systolic blood pressure (SBP) is an important predictor of cardiovascular disease (CVD) outcomes. Lowering SBP has been shown to reduce CVD morbidity and mortality, but the optimal SBP target continues to be a topic of intense debate. The Systolic Blood Pressure Intervention Trial (SPRINT) reported a significantly lower risk for CVD outcomes and all-cause mortality by targeting SBP <120 mmHg compared with <140 mmHg in a population of hypertensive persons at high CV risk. In this review, we discuss the strengths, limitations, and generalizability of SPRINT findings to other hypertensive populations that were excluded from the trial, including those with diabetes or prior stroke, <50 years old, and at lower CVD risk. We will focus on the implications of SPRINT findings for appropriate BP targets in high-risk groups of hypertensive persons, including the elderly and those with chronic kidney disease (CKD). We will also address the cost-effectiveness of intensive BP treatment as implemented in SPRINT and the implications of SPRINT for health care policy and future BP guidelines.

Cardiovascular care for older adults: hypertension and stroke in the older adult.

Abstract: Hypertension and cerebrovascular disease incidence and prevalence rise dramatically with age, owing to longer exposure time to age-associated alterations in vascular function and structure and cardiovascular risk factors. This chapter is aimed at connecting age-related alterations in vascular function and structure to the resultant target organ damage, and to raise awareness of unique presentations and treatment strategies for hypertension and stroke in older adults. Much of this chapter builds on the unique physiology of the older adult, as previously described by Dai, et al.,[1] and applied to the conditions of hypertension and stroke here. Arterial changes with aging include increased calcium deposition, collagen content, and collagen cross-linking, increased intima-media thickness, increased reactive oxygen species and a pro-inflammatory state and increased apoptosis of vascular smooth muscle cells. These changes lead to stiffer vessels that demonstrate less systolic compliance and diastolic elasticity, increased pulse wave velocity, and increased pulse pressure. The early reflected wave and augmented systolic pressure characteristic of arterial stiffness create greater demands on the left ventricle, resulting in left ventricular hypertrophy and impaired relaxation, which ultimately lead to increased left atrial pressure and size. Coupled with changes in endothelial function, neurohormonal regulation and renal function, these hemodynamic processes create the unique physiology of the older adult, manifest by isolated systolic hypertension, target organ damage and cardiovascular disease (CVD).

Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT])

Abstract: Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.

SPS3 Evidence Supports Intensive Blood Pressure Control.

Abstract: Interest in identifying the most appropriate targets for systolic blood pressure (SBP) lowering to reduce cardiovascular events in persons with hypertension has been piqued by the widely publicized results of the Systolic Blood Pressure Intervention Trial (SPRINT).1,2 SPRINT found overwhelming benefit (25% reduction in the primary composite outcome of myocardial infarction [MI], acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure, or death from cardiovascular causes) and 27% reduction in all-cause mortality among participants randomly assigned to a SBP target of <120 mm Hg (intensive treatment) in comparison with <140 mm Hg (standard treatment). In contrast, serious adverse events, including acute kidney injury or acute renal failure that contributed to hospitalizations or emergency department visits were significantly more common in the intensive treatment group (4.4% versus 2.6%, hazard ratio, 1.71; P <0.001). Among those who did not have chronic kidney disease (CKD) at baseline, incident CKD, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% to a level of <60 mL·min–1·1.73 m–2 occurred more frequently in the intensive treatment group (1.21%/y versus 0.35%/y). Among those with CKD at baseline, few reached the primary renal end point of decrease in eGFR ≥50% or end-stage renal disease (ESRD). Incident albuminuria, another measure of kidney damage, did not differ between treatment groups. The investigators concluded that available data provide no evidence of substantial permanent kidney injury associated with the lower SBP goal in SPRINT, but that the possibility of such adverse outcomes cannot be excluded and that longer follow-up data that include more clinical outcomes and analyses of rates of fall in eGFR are needed to address this important issue. Article see p 584 A recent post hoc analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial in this …

The polypill: an emerging treatment alternative for secondary prevention of cardiovascular disease

Abstract: Thomas Hedner, Sverre E. Kjeldsen, Krzysztof Narkiewicz and Suzanne Oparil Department of Medicine, University of Göteborg, Sahlgrenska Academy, Göteborg, Sweden; Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway; Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland; Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, USA

Sy 11-3 hypertension in women: more dangerous than in men?

Abstract: Heart disease, stroke, and kidney failure are leading causes of death worldwide, and hypertension is a significant risk factor for each. Hypertension is less common in women, compared to men, in those younger than 45 years of age. This trend is reversed in those 65 years and older. In the US between 2011-2014, the prevalence of hypertension in women and men by age group was 6% vs 8% (18-39 years), 30% vs 35% (40-59 years), and 67% vs 63% (60 years and over). Awareness, treatment, and control rates differ between genders with women being more aware of their diagnosis (85% vs 80%), more likely to take their medications (81% vs 71%) and more frequently having controlled hypertension (55% vs 49%). Analysis of >12,000 patient visits with primary care physicians in the US showed no gender difference in the number of anti-hypertensive medications, but did reveal women were more commonly prescribed diuretics and less frequently prescribed ACE-inhibitors.Data on blood pressure (BP) and hypertension prevalence have traditionally been based on manual/automated sphygmomanometer measurements in office. However, extensive epidemiologic data indicate that up to 30% of persons diagnosed with hypertension in office are normotensive outside of clinic. Multiple large population based meta-analyses have shown the superiority of ambulatory blood pressure monitoring (ABPM) and home BP monitoring (or self-monitoring) to in-clinic BP measurements in predicting cardiovascular outcomes (cardiovascular death, stroke, and cardiac/coronary events). Further, night-time BP recorded by ABPM has emerged as a better predictor of total mortality, stroke, and cardiovascular death in patients with hypertension and a history cardiovascular disease (CVD) than either day-time ABPM or in-clinic BP measurements. Importantly, the United States Preventive Services Task Force is now recommending ABPM in all patients prior to initiation of anti-hypertensive treatment as a Grade-A recommendation. ABPM data show a higher percentage of women (43%) than men (34%) have white coat hypertension (elevated in clinic BP, normal out of clinic BP). White coat hypertension has been associated with development of sustained hypertension and increased stroke risk on long term follow-up. In contrast, masked hypertension (elevated out of clinic BP, normal in clinic BP), which has been associated with increased cardiovascular risk, is less common in women compared to men. The prevalence of masked hypertension in women increases with body mass index (adjusted OR = 1.65 for BMI≥27, 95% CI = 1.14-2.39) and alcohol intake (adjusted OR = 2.12 for at least six drinks per week, 95% CI = 1.34-3.35), perhaps accounting for the increased rate of cardiovascular outcomes in this patient group.Randomized controlled trials (RCTs) with CVD outcomes have provided definitive evidence that BP lowering medications benefit hypertensive women. While these trials have largely shown similar CVD outcome benefits in both genders, some differences in response to therapy have been reported. In the ALLHAT study, amlodipine, compared to lisinopril, was associated with a greater reduction in BP, as well as a decreased stroke rate in women. In the VALUE study, cardiovascular morbidity/mortality was higher with valsartan than with amlodipine in women. In the LIFE study, a lower primary composite endpoint (CVD death, stroke, and myocardial infarction) was seen in women treated with losartan. The BP Lowering Treatment Trialists' Collaboration overview of 31 RCTs included comparisons of active agents with placebos, intensive vs less intensive anti-hypertensive medications, and one active agent versus another. In all cases, average baseline BP was higher for women than men, but BP reduction was comparable between genders. No differences in the effects of various anti-hypertensive regimens on CVD outcomes by gender were identified. However, clinically significant gender specific adverse effects of various anti-hypertensive drug classes have been identified. Women more commonly develop hyponatremia/hypokalemia from diuretic therapy; men more frequently develop gout. Women are 3 times more likely to develop an ACE-inhibitor related cough, and more commonly experience CCB-related peripheral edema and minoxidil-induced hirsutism. Importantly, ACEIs/ARBs, direct renin inhibitors, and mineralocorticoid antagonists are contraindicated in women of reproductive age due to the potential of developing fetal abnormalities. Thiazide type diuretics are preferred for the use in elderly women because of decreased risk of hip fractures.Several forms of hypertension, including post-menopausal, oral contraceptive (OCP) induced, and pregnancy related hypertension occur only in women. Following menopause, there is an age independent increase in systolic BP thought to be secondary to the withdrawal of endogenous estrogen, increased salt sensitivity, diminished endothelial nitric oxide production, and increased angiotensin II receptor expression. OCP use is associated with increases in both BP and risk of cardiovascular events, which are reversible with cessation of OCP use. Hypertension in pregnancy (including chronic hypertension, gestational hypertension, preeclampsia, and eclampsia) is associated with increased maternal and fetal cardiovascular and non-cardiovascular risk during pregnancy and long-term mortality risk, particularly for Alzheimer disease, stroke, diabetes, and ischemic heart disease.

HOPE-3 and SPRINT: two landmark trials with different outcomes?

Abstract: clinical trials beginning with the landmark VA trial. 1 In this trial, 143 men with a diastolic pressure 115‐129 mm Hg were randomized to active treatment with hydrochlorothiazide (HCTZ) plus reserpine plus hydralazine or placebo. Dramatic reductions in cardiovascular disease (CVD) outcomes (two cases of cerebrovascular thrombosis and multiple drug toxicity) occurred in the active treatment group compared to 27 CVD outcomes (hypertensive retinopathy, congestive heart failure, increasing azotemia, cerebrovascular thrombosis, transient ischemic attacks, cerebral hemorrhage, myocardial infarction, and severely elevated blood pressure (BP)) and four deaths in the placebo group. This study soundly refuted that the then prevailing hypothesis that ‘‘hypertension may be an important compensation mechanism which should not be tampered with.’’ 2 Many subsequent controlled clinical trials have shown the CVD benefit of lowering BP in patients with various forms of hypertension, diastolic and isolated systolic, severe and less severe, among different racial/ethnic and age groups and associated with a variety of comorbid

Anxiety and sleep as potential mechanisms underlying heightened sympathetic tone in patients with refractory hypertension

Abstract: (p1⁄40.003). Adolescents with HABP showed significant higher values than normotensives in the AASI, these values were: 0.483 0.3 vs. 0.390 0.2 (p<0.0.04). Spearman Correlation shows a statistically significant correlation between HABP and AASI (r1⁄40.2197, P<0.02) In conclusion, there is a very high prevalence of HABP in adolescent population. In this age group, the AASI is associated with the presence of high ambulatory BP. This condition, associated with arterial stiffness, should be assessed in adolescents with high values of ambulatory blood pressure, because they should be in high cardiovascular risk.

Purification of an angiotensin II binding protein by using antibodies to a peptide encoded by angiotensin II complementary RNA (angiotensin II receptor/complementary peptides/molecular recognition code/immunoaffinity chromatography)

Abstract: We have generated a monospecific antibody to a synthetic peptide encoded by an RNA complementary to the mRNA for angiotensin II (All) and determined whether this antibody recognizes the All receptor. We demonstrate that the antibody competes specifically with '251_labeled All for the same binding site on rat adrenal membranes. Further- more, we show that this antibody inhibits the secretion of aldosterone from cultured rat adrenal cells, suggesting that the antibody recognizes the biologically relevant All receptor. Finally, we demonstrate that antibody to the complementary peptide can be used to immunoaffinity-purify a protein of Mr 66,000 that specifically binds radiolabeled All.