Showing papers by "Joseph L. Izzo published in 2019"

Effect of Sacubitril-Valsartan vs Enalapril on Aortic Stiffness in Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial

Abstract: Importance Compared with enalapril, sacubitril-valsartan reduces cardiovascular mortality and heart failure hospitalization in patients with heart failure and reduced ejection fraction (HFrEF). These benefits may be related to effects on hemodynamics and cardiac remodeling. Objective To determine whether treatment of HFrEF with sacubitril-valsartan improves central aortic stiffness and cardiac remodeling compared with enalapril. Design, Setting, and Participants Randomized, double-blind clinical trial of 464 participants with heart failure and ejection fraction of 40% or less enrolled across 85 US sites between August 17, 2016, and June 28, 2018. Follow-up was completed on January 26, 2019. Interventions Randomization (1:1) to sacubitril-valsartan (n = 231; target dosage, 97/103 mg twice daily) vs enalapril (n = 233; target dosage, 10 mg twice daily) for 12 weeks. Main Outcomes and Measures The primary outcome was change from baseline to week 12 in aortic characteristic impedance (Zc), a measure of central aortic stiffness. Prespecified secondary outcomes included change from baseline to week 12 in N-terminal pro–B-type natriuretic peptide, ejection fraction, global longitudinal strain, mitral annular relaxation velocity, mitral E/e′ ratio, left ventricular end-systolic and end-diastolic volume indexes (LVESVI and LVEDVI), left atrial volume index, and ventricular-vascular coupling ratio. Results Of 464 validly randomized participants (mean age, 67.3 [SD, 9.1] years; 23.5% women), 427 completed the study. At 12 weeks, Zc decreased from 223.8 to 218.9 dyne × s/cm5in the sacubitril-valsartan group and increased from 213.2 to 214.4 dyne × s/cm5in the enalapril group (treatment difference, −2.2 [95% CI, −17.6 to 13.2] dyne × s/cm5;P = .78). Of 9 prespecified secondary end points, no significant between-group difference in change from baseline was seen in 4, including left ventricular ejection fraction (34%-36% with sacubitril-valsartan vs 33 to 35% with enalapril; treatment difference, 0.6% [95% CI, −0.4% to 1.7%];P = .24). However, greater reductions from baseline were seen with sacubitril-valsartan than with enalapril in all others, including left atrial volume (from 30.4 mL/m2to 28.2 mL/m2vs from 29.8 mL/m2to 30.5 mL/m2; treatment difference, −2.8 mL/m2[95% CI, −4.0 to −1.6 mL/m2];P Conclusions and Relevance Treatment of HFrEF with sacubitril-valsartan, compared with enalapril, did not significantly reduce central aortic stiffness. The study findings may provide insight into mechanisms underlying the effects of sacubitril-valsartan in HFrEF. Trial Registration ClinicalTrials.gov Identifier:NCT02874794

Antihyperglycemic and Blood Pressure Effects of Empagliflozin in Black Patients With Type 2 Diabetes Mellitus and Hypertension.

Abstract: Background: Empagliflozin, a sodium-glucose cotransporter 2 inhibitor indicated for type 2 diabetes mellitus (T2DM), can lower blood pressure (BP) and reduce cardiovascular mortality in patients wi...

Pulse Wave Velocities Derived From Cuff Ambulatory Pulse Wave Analysis.

Abstract: Pulse wave velocity (PWV), a measure of arterial stiffness, is an independent risk factor for cardiovascular morbidity and mortality. We investigated the relationship of ambulatory brachial cuff-ba...

Long-term BP control and vascular health in patients with hyperaldosteronism treated with low-dose, amiloride-based therapy.

Abstract: Whether aldosterone itself contributes directly to macro- or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long-term single-practice experience in 5 patients with chronic hyperaldosteronism (HA, including 3 with glucocorticoid remediable aldosteronism, GRA) treated with low-dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5-10 (mean 7) mg daily for 14-28 (mean 20) years. Except for 1 GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normal or near-normal within 1-4 weeks after starting amiloride and office BP's were well controlled for 20 years thereafter. Vascular studies and 24-hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, and reflection magnitude) were assessed after a mean of 18 years as were regional pulse wave velocities, pulse stiffening ratio, ankle-brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio. All indicators were completely normal in all patients after 18 years of amiloride, and none had a cardiovascular event during the 20-year mean follow-up. We conclude that long-term ENaC blockade can normalize BP and protect macro- and microvascular function in patients with HA. This suggests that (a) any vasculopathic effects of aldosterone are mediated via ENaC, not MR activation itself, and are fully preventable or reversible with ENaC blockade or (b) aldosterone may not play a major BP-independent role in human macro- and microcirculatory diseases. These and other widely divergent results in the literature underscore the need for additional studies regarding aldosterone, ENaC, and vascular disease.

Maintenance of long-term blood pressure control and vascular health by low-dose amiloride-based therapy in hyperaldosteronism.

Abstract: Whether aldosterone itself contributes directly to macro- or microcirculatory disease in man or to adverse cardiovascular outcomes is not fully known. We report our long-term single-practice experience in an unusual group of five patients with chronic hyperaldosteronism (HA, including three with glucocorticoid-remediable aldosteronism, GRA) treated with low-dose amiloride (a specific epithelial sodium channel [ENaC] blocker) 5-10 (mean 7) mg daily for 14-28 (mean 20) years. Except for one GRA diagnosed in infancy, all had severe resistant hypertension. In each case, BP was normalized within 1-4 weeks after starting amiloride and office BP's remained well controlled throughout the next two decades. 24-hour ambulatory BP monitoring with pulse wave analysis (cardiac output, vascular resistance, augmentation index, reflection magnitude), regional pulse wave velocities, pulse stiffening ratio, ankle-brachial index, serum creatinine, estimated glomerular filtration rate, and spot urinary albumin:creatinine ratio were measured after a mean of 18 years; all of these indicators were essentially normal. Over two additional years of observation (100 patient-years total), no cardiovascular or renal event occurred. We conclude that long-term ENaC blockade with amiloride can normalize BP and protect macro- and microvascular function in patients with HA. This suggests that either (a) putative vasculopathic effects of aldosterone are mediated via ENaC or (b) aldosterone may not play a direct role in age-dependent vasculopathic changes in humans independent of blood pressure. These findings, coupled with our literature review in both animal and human results, underscore the need for additional studies.

Independence of blood pressure from heart rate in established hypertension: counter-regulatory impact of rate-volume and rate-resistance compensations

Abstract: Objective:Blood pressure and heart rate are cardiovascular risk factors but little attention has been paid to the pathophysiology of heart rate-blood pressure interactions, especially during 24-hour ambulatory monitoring.Design and method:We studied individuals with known hypertension using 24-hour

Barriers to blood pressure control initiatives: Regional diversity, inadequate measurement techniques, guideline inconsistencies, and health disparities.

Abstract: Community and regional health improvement projects have had widely varying degrees of success. Impactful voluntary efforts are not com‐ mon, making the 5‐year results of the Rochester High Blood Pressure Collaborative (Fortuna, et al in this issue of the Journal) noteworthy. The primary goals of the Rochester program were to (1) improve hyperten‐ sion control rates and (2) reduce health disparities. This collaborative ef‐ fort involved academic physicians, community practices, hospitals, and insurers and was funded through a special hospital charge. The authors used the words “lessons learned” in their title and admonished those planning future health initiatives to (1) anticipate a response plateau, (2) identify the specific needs of important subpopulations and develop specific strategies to address and reduce health disparities, (3) recognize variation among practices treating patients with low socioeconomic status (SES), (4) anticipate new outcome measures, and (5) continually seek best practices and barriers to success. The initiative apparently succeeded: In 226 843 patients from 193 practices followed from 2011 to 2016, overall hypertension control rates improved from 61.9% to 69.5% but more so in whites (73.7%‐81.5%) than blacks (58.8%‐64.7%) and the effort deserves a measure of respect. However, many issues cloud the present effort and it is not entirely clear that the experience can be easily reproduced elsewhere. My concern can be arbitrarily di‐ vided into four critical areas: First, whether Rochester is different from other communities, and then whether the three most universal and sub‐ stantial barriers to better BP control were successfully overcome: (1) in‐ adequate blood pressure measurement techniques, (2) the proliferation and vagaries of ever‐changing treatment guidelines, and (3) the actual impact of health disparities. Any one of these concerns presents an enormous challenge, and none were squarely addressed by Fortuna and colleagues. This not to say that other locales should not try to organize health care demonstration projects or that elements of the Rochester program cannot be emulated. What is most important is to thoroughly evaluate their methods and results in the context of their region and the known barriers to better blood pressure control. 1 | THE LOC AL HE ALTHC ARE SYSTEM