Showing papers by "Suzanne Oparil published in 2019"

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.

Abstract: Importance There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration ClinicalTrials.gov Identifier:NCT01206062

Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions.

Abstract: Importance The effect of intensive blood pressure lowering on brain health remains uncertain. Objective To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3(difference, 0.92 cm3[95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3(difference, 1.45 cm3[95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, −0.54 cm3[95% CI, −0.87 to −0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3(difference, −30.6 cm3[95% CI, −32.3 to −28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3(difference, −26.9 cm3[95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, −3.7 cm3[95% CI, −6.3 to −1.1]). Conclusions and Relevance Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration ClinicalTrials.gov Identifier:NCT01206062

Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial

Abstract: Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 m...

Treatment of Resistant and Refractory Hypertension.

Abstract: Resistant hypertension (RHTN) is defined as uncontrolled blood pressure despite the use of ≥3 antihypertensive agents of different classes, including a diuretic, usually thiazide-like, a long-acting calcium channel blocker, and a blocker of the renin- angiotensin system, either an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin receptor blocker), at maximal or maximally tolerated doses. Antihypertensive medication nonadherence and the white coat effect, defined as elevated blood pressure when measured in clinic but controlled when measured outside of clinic, must be excluded to make the diagnosis. RHTN is a high-risk phenotype, leading to increased all-cause mortality and cardiovascular disease outcomes. Healthy lifestyle habits are associated with reduced cardiovascular risk in patients with RHTN. Aldosterone excess is common in patients with RHTN, and addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen is effective at getting the blood pressure to goal in most of these patients. Refractory hypertension is defined as uncontrolled blood pressure despite use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses. Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying RHTN, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity.

Epicardial Adipose Tissue and Cardiovascular Disease.

Abstract: Epicardial adipose tissue has been associated with the development/progression of cardiovascular disease. We appraise the strength of the association between epicardial adipose tissue and development/progression of cardiovascular diseases like coronary artery disease, atrial fibrillation, and heart failure with preserved ejection fraction. Cross-sectional clinical and translational correlative studies have established an association between epicardial adipose tissue and progression of coronary artery disease. Recent studies question this association and underline the need for longitudinal studies. Epicardial adipose tissue also plays a definite role in the pathobiology of atrial fibrillation and its recurrence after ablation. In contrast to an early paradigm, epicardial adipose tissue does not appear to play a key role in the pathogenesis of heart failure with preserved ejection fraction in obese patients. The association of epicardial adipose tissue with atrial fibrillation is robust. In contrast, the association of epicardial adipose tissue with coronary artery disease and heart failure with preserved ejection fraction is tenuous. Additional research, including longitudinal studies, is needed to confirm or refute these proposed associations.

Sex Differences in Hypertension and Stroke Risk in the REGARDS Study: A Longitudinal Cohort Study.

Abstract: Little is known about whether the relationship between hypertension and ischemic stroke differs by sex. We examined sex differences in the association between hypertension severity and treatment an...

Out-of-clinic sympathetic activity is increased in patients with masked uncontrolled hypertension

Abstract: Masked uncontrolled hypertension (MUCH) is defined as controlled automated office blood pressure (BP; AOBP <135/85 mm Hg) in-clinic in patients receiving antihypertensive medication(s) but uncontro...

Effect of Intensive Blood Pressure Reduction on Left Ventricular Mass, Structure, Function, and Fibrosis in the SPRINT-HEART.

Abstract: In observational studies, left ventricular mass (LVM) and structure are strong predictors of mortality and cardiovascular events. However, the effect of hypertension treatment on LVM reduction and its relation to subsequent outcomes is unclear, particularly at lower blood pressure (BP) targets. In an ancillary study of SPRINT (Systolic Blood Pressure Intervention Trial), where participants were randomly assigned to intensive BP control (target systolic BP target <120 mm Hg) versus standard BP control (<140 mm Hg), cardiac magnetic resonance imaging was performed at baseline and 18-month follow-up to measure: LVM, volumes, ejection fraction, and native T1 mapping for myocardial fibrosis. At baseline, 337 participants were examined (age: 64±9 years, 45% women); 300 completed the 18-month exam (153 intensive control and 147 standard control). In the intensive versus standard BP control group at 18 months, there was no difference in change in LVM (mean±SE =-2.7±0.5 g versus -2.3±0.7 g; P=0.368), ejection fraction, or native T1 ( P=0.79), but there was a larger decrease in LVM/end-diastolic volume ratio (-0.04±0.01 versus -0.01±0.01; P=0.002) a measure of concentric LV remodeling. There were fewer cardiovascular events in the intensive control group, but no significant association between the reduced events and change in LVM or any other cardiac magnetic resonance imaging measure. In SPRINT-HEART, contrary to our hypothesis, there were no significant between-group differences in LVM, function, or myocardial T1 at 18-month follow-up. These results suggests that mediators other than these LV measures contribute to the improved cardiovascular outcomes with intensive BP control.

Sustained blood pressure control and coronary heart disease, stroke, heart failure, and mortality: An observational analysis of ALLHAT

Abstract: Achieving blood pressure (BP) control is associated with lower cardiovascular disease (CVD) risk, but less is known about CVD risk associated with sustained BP control over time. This observational analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was restricted to participants with four to seven visits with systolic BP (SBP) measurements during a 22-month period (n = 24 309). The authors categorized participants as having sustained BP control (SBP < 140 mm Hg) at 100%, 75% to <100%, 50% to <75%, and <50% of visits during this period. Outcomes included fatal coronary heart disease (CHD)/nonfatal myocardial infarction (MI), stroke, heart failure (HF), a composite CVD outcome (fatal CHD/nonfatal MI, stroke, or HF), and mortality. Hazard ratios (HRs) for the association of category of sustained BP control for each outcome were obtained using proportional hazards models. SBP control was present among 20.0% of participants at 100%, 16.4% at 75% to less than 100%, 27.0% at 50% to less than 75%, and 36.6% at less than 50% of visits. Compared to those with SBP control at 100% visits, adjusted HR (95% CI) among those with SBP control at <50% of visits was 1.16 (0.93-1.44) for fatal CHD/nonfatal MI, 1.71 (1.26-2.32) for stroke, 1.63 (1.30-2.06) for HF, 1.39 (1.20-1.62) for the composite CVD outcome, and 1.14 (0.99-1.30) for mortality. Sustained SBP control may be beneficial for preventing stroke, HF, and CVD outcomes in adults taking antihypertensive medication.

Masked Uncontrolled Hypertension Is Not Attributable to Medication Nonadherence.

Abstract: Masked uncontrolled hypertension (MUCH) in treated hypertensive patients is defined as controlled automated office blood pressure (BP; <135/85 mm Hg) in-clinic but uncontrolled out-of-clinic BP by ...

Prevention of Heart Failure in Hypertension-Disentangling the Role of Evolving Left Ventricular Hypertrophy and Blood Pressure Lowering: The ALLHAT Study.

Abstract: Background Hypertension is a known risk factor for heart failure (HF), possibly via the mechanism of cardiac remodeling and left ventricular hypertrophy (LVH). We studied the extent to which blood ...

Urinary biomarkers of tubular damage are associated with mortality but not cardiovascular risk among systolic blood pressure intervention trial participants with chronic kidney disease

Abstract: Background: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. Methods: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. Results: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01–1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02–1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Conclusions: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

New data on antihypertensive drugs and risk of cancer: should we worry?

Abstract: Cardiovascular disease (CVD) and cancer are the two leading causes of mortality worldwide. Over the last four decades, there has been a trend towards a decrease in age-standardized deaths due to bo...

Clinical characteristics, antihypertensive medication use and blood pressure control among patients with treatment-resistant hypertension: the Survey of PatIents with treatment ResIstant hyperTension study.

Abstract: Objective:We evaluated the characteristics of patients with treatment-resistant hypertension (TRH) and the prevalence of TRH in a large multicountry sample of specialist tertiary centres.Methods:The Survey of PatIents with treatment ResIstant hyperTension (SPIRIT) study was a retrospective review of

Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction: Potential Role of Diuretics.

Abstract: Objectives This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study. Background SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications. Methods Detailed use of medication data prospectively collected throughout the trial were examined. Results ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop ( Conclusions No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062 ).

Induced pluripotent stem cell-derived endothelial cells attenuate lipopolysaccharide-induced acute lung injury

Abstract: We have developed a novel approach to address neutrophil-mediated inflammation and endothelial damage by targeted delivery of rat-induced pluripotent stem cell (iPS)-derived endothelial cell (ECs) ...

Will we ever use angiotensin receptor neprilysin inhibition (ARNi) for the treatment of hypertension

Abstract: The Renin-Angiotensin–Aldosterone System (RAAS) is central to blood pressure (BP) control. Chronic overactivation of the RAAS occurs in a majority of cardiovascular disorders including hypertension...

Lower Blood Pressure Thresholds Raise the Bar in Pregnancy

Abstract: In this issue, Hu et al assess the impact of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) Hypertension Guideline on the diagnosis of gestational hypertension and associated maternal and neonatal risks. They used data from a birth cohort of 16 345 women without chronic (preexisting) hypertension who delivered at Wuhan Women and Children Medical Care Center in Wuhan, China, from 2012 to 2016. Their main findings were that 4100 (25%) of the women had gestational hypertension defined by the 2017 ACC/AHA Guideline (Figure 1) and that gestational hypertension was significantly associated with altered hepatic, renal and coagulation function in mothers, and with adverse perinatal outcomes, including preterm and early term births, and small for gestational age newborns. The authors concluded that application of the 2017 ACC/AHA definition of hypertension, systolic blood pressure (BP) >130 mm Hg or diastolic BP >80 mm Hg, to pregnant women would increase the prevalence of gestational hypertension ≈6-fold and could provide more precise detection and even prevention of gestational hypertension, thereby reducing the risk of adverse outcomes for mothers and newborns.

Prevention of heart failure in hypertension – disentangling the role of evolving left ventricular hypertrophy and blood pressure lowering: the ALLHAT study

Abstract: Background Hypertension (HTN) is a known risk factor for heart failure (HF), possibly via the mechanism of cardiac remodeling and left ventricular hypertrophy (LVH). We studied how much blood pressure (BP) change and evolving LVH contribute to the effect that lisinopril, doxazosin, amlodipine have on HF compared to chlorthalidone. Methods We conducted causal mediation analysis of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) data. ALLHAT participants with available serial ECGs and BP measurements were included (n=29,892; mean age 67±4 y; 32% black; 56% men): 11,008 were randomized to chlorthalidone, 5,967 – to doxazosin, 6,593 – to amlodipine, and 6,324 – to lisinopril. Evolving ECG-LVH, and BP-lowering served as mediators. Incident symptomatic HF was the primary outcome. Linear regression (for mediator) and logistic regression (for outcome) models were adjusted for mediator-outcome confounders (demographic and clinical characteristics known to be associated both with both LVH/HTN and HF). Results A large majority of participants (96%) had ECG-LVH status unchanged; 4% developed evolving ECG-LVH. On average, BP decreased by 11/7 mmHg. In adjusted Cox regression analyses, progressing ECG-LVH [HR 1.78(1.43-2.22)], resolving ECG-LVH [HR 1.33(1.03-1.70)], and baseline ECG-LVH [1.17(1.04-1.31)] carried risk of incident HF. After full adjustment, evolving ECG-LVH mediated 4% of the effect of doxazosin on HF. Systolic BP-lowering mediated 12% of the effect of doxazosin, and diastolic BP-lowering mediated 10% effect of doxazosin, 7% effect of amlodipine, and borderline 9% effect of lisinopril on HF. Conclusions Evolving ECG-LVH and BP change account for 4-13% of the mechanism by which antihypertensive medications prevent HF.

The PARAGON Heart Failure trial – ongoing investigation of the angiotensin receptor antagonist/neprilysin inhibitor sacubitril/valsartan in heart failure patients with hypertension and preserved ejection fraction

Abstract: Novel angiotensin-receptor antagonist/neprilysin inhibitors (ARNi) seek to exploit the clinical benefits of combining renin-angiotensin-aldosterone-system (RAAS) antagonism and neutral endopeptidas...

Blood Pressure and the Electronic Health Record: A Work in Progress.

Abstract: See Article Ayala Solares et al

Op0208 effect of serum urate lowering with allopurinol on blood pressure in young adults

Abstract: Background The association between serum urate and hypertension continues to be controversial. Animal models and studies in adolescents provided strong support of urate- lowering therapy (ULT) efficacy to improve early hypertension (1), while one recent randomized-controlled study in adults failed to find benefit (2). Objectives To test the hypothesis that serum urate reduction with allopurinol would lead to blood pressure reductions in young adults with pre-hypertension. Methods Single center, double-blinded, crossover trial in which participants were randomly assigned to allopurinol (300 daily mg) or placebo for a period of one month each. Adults ages 18-40, with baseline systolic blood pressure (SBP) ≥ 120 and 297.4 µmol/L) or ≥ 4.0 mg/dL (237.9 µmol/L) (men or women, respectively) were enrolled. Main exclusion criteria included chronic kidney disease, gout, or use of ULTs. The primary outcome was change from baseline in SBP assessed by 24 hour ambulatory blood pressure monitoring. Safety assessments were also conducted. Results 99 participants were randomized, and 82 completed study participation (Table 1). Serum urate decreased by -1.33 ± 1.21 mg/dL (-79.1 ± 72.0 µmol/L) during the allopurinol period (p 6.5 mg/dL (> 386.7 µmol/L) at baseline visit. No allopurinol hypersensitivity events or other serious adverse events were observed. Conclusion In the intention-to-treat analysis, urate -lowering therapy with allopurinol in young adults did not lead to reductions in blood pressure when compared with placebo. Blood pressure reductions with allopurinol may be limited only to participants with higher baseline serum urate levels. References [1] Feig DI, Soletsky B, Johnson RJ. JAMA. 2008;300:924-32. [2] McMullan CJ, Borgi L, Fisher N, et al. Clin J Am Soc Nephrol. 2017;12:807-16. Disclosure of Interests Angelo Gaffo: None declared, David Calhoun: None declared, Elizabeth Rahn: None declared, Suzanne Oparil: None declared, Paul Muntner Grant/research support from: Dr. Muntner declares research grant from Amgen, Peng Li: None declared, David Redden: None declared, Tanja Dudenbostel: None declared, Jeff Foster: None declared, Stephanie Biggers: None declared, Daniel Feig: None declared, Kenneth Saag Grant/research support from: Amgen, Ironwood/AstraZeneca, Horizon, SOBI, Takeda, Consultant for: Abbvie, Amgen, Ironwood/AstraZeneca, Bayer, Gilead, Horizon, Kowa, Radius, Roche/Genentech, SOBI, Takeda, Teijin

State of the Art: the Not-So-Great Wall of America.

Abstract: This paper aims to review the literature regarding the impact of Donald Trump’s candidacy and presidency on the health of immigrants in America. The increase in detentions of alleged undocumented immigrants under the Trump presidency, especially his administration’s attempts to detain children apart from their families, have placed thousands into conditions that can have long-lasting physical and mental health effects. Similarly, the Trump administration’s efforts to increase deportations and restrict legal immigration has lead to immigrants’ seeking fewer health-care resources for fear of jeopardizing their or their loved ones’ chances of remaining in this country. The rhetoric used and policies pursued by Donald Trump have had a measurable adverse impact on the health of documented and undocumented immigrants in America.

The PARAGON-Heart failure trial - another disappointment for heart failure patients with hypertension and preserved ejection fraction.

Abstract: Novel angiotensin receptor antagonist/neprilysin inhibitors (ARNIs) seek to exploit the clinical benefits of combining renin-angiotensin-aldosterone-system (RAAS) antagonism and neutral endopeptida...

Need for multiple risk reduction strategies in clinical trials enrolling high risk patients - FOURIER investigating PCSK-9 inhibitor to lower cholesterol revisited.

Abstract: Hypertension is the most prevalent cardiovascular risk factor [1]. Many people with hypertension also have comorbid conditions or risk factors for which novel treatment strategies are being tested ...