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Introduction
Hypertension, arterial structure and function, heart failure, cardiorenal medicine
Current institution
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October 1988 - May 2016
Publications
Publications (324)
Mean arterial pressure (MAP) is often estimated from cuff systolic (S) and diastolic (D) blood pressure (BP) using a fixed arterial form factor (FF, usually 0.33). If MAP is measured directly, a true FF can be calculated: FF = [MAP–DBP]/[SBP–DBP]. Because waveform shapes vary, true FF should also vary and MAP accuracy will be affected. We studied f...
Mean arterial pressure (MAP) is often estimated from cuff systolic (S) and diastolic (D) blood pressure (BP) using a fixed arterial form factor (FF, usually 0.33). If MAP is measured accurately, a true FF can be calculated: FF = [MAP–DBP] / [SBP–DBP]. Because waveform shapes vary, true measured FF should also vary and MAP accuracy may be affected....
Objective:
Mean arterial pressure (MAP) is often estimated from systolic (S) and diastolic (D) blood pressure (BP) using a constant "form factor'' (FF), usually MAP = DBP + 0.33*pulse pressure (PP), yet accurate measurement requires pulse wave analysis (PWA) and waveform integration. MAP is constant across all conduit arteries but PP increases dis...
Objective:
Blood pressure (BP) is highly variable but the concomitant variations of the underlying hemodynamic components [heart rate (HR), stroke volume (SV), and total vascular resistance (TVR)] are not known. We postulated that covariance (cov) analysis of 24-hour ambulatory pulse wave analysis (PWA) could reveal relevant trends in hemodynamic...
The complex topic of short- and long-term blood pressure (BP) variability confounds the diagnosis, classification, and management of hypertension. True pathophysiologic BP variation (systematic and non-systematic deviations between- and within-individuals) is related to heart rate, respiration, complex responses of the sympathetic nervous system, v...
BP is highly variable within and between individuals but the impact of variation in underlying hemodynamic components is unknown. We tested the feasibility and clinical associations of quantitated variances in MAP and its hemodynamic components [heart rate (HR), stroke volume (SV) and total vascular resistance (TVR)] obtained by 24-hr ambulatory pu...
Accurate mean arterial pressure (MAP) measurement requires an integrated arterial pressure waveform but MAP is often estimated from systolic (S) and diastolic (D) BP using a fixed form factor (FF, usually 0.33): MAP = DBP + FF*pulse pressure (PP), also solvable for FF if MAP is known. MAP is constant in the arterial tree but central (c) PP is lower...
Background:
Treatment with sacubitril-valsartan reduces mortality and heart failure (HF) events in HF with reduced ejection fraction and may reduce HF hospitalization in women with HF with preserved ejection fraction.
Methods:
EVALUATE-HF randomized 464 participants (109 women) with HF with reduced ejection fraction to sacubitril-valsartan or en...
Windkessel (WK) models have often been used to simulate the arterial circulation. We studied a critical characteristic of WK function, the arterial pressure-decay constant tau, to test whether all arterial regions share the same WK characteristics, which should theoretically be related to arterial stiffness. We performed carotid and forearm arteria...
To investigate the dynamic relationships among Heart Rate (HR) and systemic hemodynamics in everyday life, we performed 24-h ambulatory pulse wave analyses (Mobil-O-Graph) in individuals with normal and elevated BP (n = 116) and in a double-blinded cross-over study where HR was varied pharmacologically (n = 24). In the whole cohort and in the low [...
Background
Compared to angiotensin-converting enzyme inhibition alone, angiotensin receptor-neprilysin inhibition reduces cardiovascular mortality and heart failure (HF) hospitalization in patients with HF and reduced ejection fraction (HFrEF). The pathophysiologic mechanisms responsible for these clinical benefits remain unclear but may be related...
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-valsarta...
Blood pressure (BP) and heart rate (HR) are independent cardiovascular risk factors but there is little information about interactions among HR, BP, and systemic hemodynamics throughout the day. We performed 24-hour ambulatory pulse wave analysis (Mobil-O-Graph, IEM, Stolberg, DE) with measurements at 20 minute intervals. Variables measured were: s...
We studied whether: 1) the carotid and forearm diastolic pressure-decay time constants (tau) are similar and 2) the associated Windkessel (WK)-derived compliance and stiffness values are also similar and are related to arterial stiffness. Ambulatory normotensive and hypertensive subjects were studied after 30 minutes of supine rest with radial and...
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...
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...
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-based oscillometric PWV (oPWV) to 2 known correlates: age and brachial systolic blood pressure (SBP). In 234 participants in the Masked Hypertension Study,...
Background:
Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated for type 2 diabetes (T2D), can lower blood pressure (BP) and reduce cardiovascular mortality in patients with T2D and pre-existing cardiovascular disease. Its effects in African Americans have been understudied.
Methods:
In this 24-week study, 150 African Am...
Introduction: We questioned whether a single Windkessel (WK) adequately describes the circulation by estimating the radial arterial diastolic pressure-decay constant (tau) and combining this with systemic hemodynamic and arterial stiffness measurements.
Methods: In the non-invasive cardiac laboratory, we performed echocardiography with simultaneous...
Introduction: The feasibility of measuring the diastolic pressure-decay constant (tau) in normal and hypertensive humans is not established and the clinical and physiological relevance of tau is not known.
Methods: Studies were performed in the non-invasive cardiac laboratory in subjects who had been supine for at least 30 minutes. Measurements inc...
Background: We have previously reported a strong negative correlation between stroke volume index (SVI) and heart rate (HR) within and between normal and hypertensive individuals and have defined the slope of the SVI-HR relationship as an index of the efficiency of rate-volume counter-regulation. SVI-HR slope may also reflect the efficiency of dias...
Aim:
It is important to know which factors predict the development of microalbuminuria in patients with diabetes mellitus type II.
Material:
Data from the Randomized Olmesartan and Diabetes Microalbuminuria Prevention Study were used to identify predictors for the new onset of microalbuminuria. Furthermore, the interaction of baseline albuminuri...
This paper aims to summarize and map contemporary views on some contentious aspects of arterial hemodynamics that have remained unresolved despite years of research. These were discussed during a workshop entitled Arterial hemodynamics: past, present and future held in London on June 14 and 15, 2016. To do this we formulated a list of potential con...
We compared the systolic blood pressure-lowering efficacy and safety of crystalline valsartan/sacubitril (LCZ696, an angiotensin receptor blocker-neprilysin inhibitor) 400 mg daily against valsartan (320 mg once daily) alone or co-administered with placebo or increasing doses of free sacubitril (50, 100, 200, or 400 mg once daily) in order to ident...
Hemodynamic in hypertension and aging
Hemodynamic trends in hypertension and aging
The effects of race and age on 24-hour mean ambulatory systolic blood pressure (maSBP) responses to sequential 4-week periods of angiotensin receptor blocker therapy (valsartan [VAL] 160 mg/d then 320 mg/d and combination VAL/hydrochlorothiazide [HCTZ] 320/12.5 mg/d) were compared in 304 patients with stage 1 or 2 hypertension. There were lesser bl...
Cross-sectional studies in the developed countries document strong relationships among age, systolic blood pressure (SBP) and pulse pressure (PP). There is little information about these trends and their impact in underdeveloped countries with different socioeconomic and lifestyle characteristics. We studied a convenience sample of 572 residents of...
Interest in arterial stiffness has been fueled by the scientific and clinical implications of its “vicious cycle” relationship with aging and systolic blood pressure. In physical terms, stiffness is the slope of the relationship between an artery’s distending pressure and its cross-sectional area or volume. Pulse wave velocity (PWV, in m/s), the mo...
Cardiovascular disease risk is continuously related to BP over the range of about 115/75 to 185/115 mmHg, yet all clinical guidelines use arbitrary cutoffs to determine acceptable antihypertensive therapy. There is substantial conflict in the results of clinical trials with respect to how low the most appropriate BP threshold should be to reduce CV...
Hemodynamic in hypertension and aging
The sympathetic nervous system (SNS) plays a permissive, if not primary causal, role in the genesis and maintenance of human essential hypertension. Excessive SNS activity in man is most apparent in early forms of hypertension (prehypertension and white-coat-type). Renal nerves are of particular interest because of their roles in modulating the act...
It is widely believed that “high-ceiling” loop diuretics are required in patients with renal impairment and that “low-ceiling” thiazides are not sufficiently potent to cause meaningful natriuresis and diuresis. If this statement is true, at what level of renal function do thiazides lose their punch? Another related issue is the enlightened use of d...
Age is the most powerful of risk factors and is related continuously to systolic BP. Yet many current guidelines have dichotomized age around a cutoff value of 55-60 years and suggest that age should affect treatment thresholds and drug choices. These opinions are contentious, not supported directly by reasonable scientific evidence, and simply rep...
Beta-blockers are antihypertensive drugs indicated for treatment of cardiomyopathies but little is known about their effects on cardiac workload in the ambulatory setting. We compared the effects of the beta-blocker nebivolol (N), the angiotensin receptor blocker valsartan (V) and combined V/N on 24-hour ambulatory central rate-pressure product (AC...
Objective: We studied characteristics central blood pressure timing (T) and pressure (P) landmarks in a reference cohort carefully assembled to mimic the age-BP relationship in the U.S. (n = 376, age 18-92). Design and method: Each participant had standard cuff BP (Omron CP705) and radial artery tonometry (Sphygmocor) after > 5 min sitting. In a su...
Objective: Relatively little is known about hypertension in underdeveloped countries, including Haiti, where a cross-sectional survey of hypertension and other common risk factors has not yet been conducted. Design and method: Residents of Fontaine in rural northern Haiti were interviewed by convenience sampling in their own homes by trained fieldw...
Objective: We compared an angiotensin receptor blocker (Valsartan, V), a beta-blocker (Nebivolol, N) and the combination (N/V) to determine their relative effects on 24-hour ambulatory hemodynamics. This pre-specified secondary analysis was performed as part of a study on ambulatory cardiac work. Copyright
An arterial pulse contour can be defined by its amplitude and timing landmarks. We studied the effects of aging and hypertension on central blood pressure landmarks in a reference cohort of normotensive and hypertensive individuals (treated and untreated (n=376, age 16-90) designed to mimic NHANES III, a representative cohort of the U.S. population...
We compared an angiotensin receptor blocker (valsartan; VAL), a beta-blocker (nebivolol; NEB) and the combination of NEB/VAL with respect to 24-hour myocardial oxygen consumption (determined by 24-hour ambulatory heart rate-central systolic pressure product [ACRPP]) and its components. Subjects with hypertension (systolic blood pressure >140 or dia...
This critique is intended to provide background for the reader to evaluate the relative clinical utilities of brachial cuff
systolic blood pressure (SBP) and its derivatives, including pulse pressure, central systolic pressure, central augmentation
index (AI), and pulse pressure amplification (PPA). The critical question is whether the newer indica...
Objective:
Prior studies indicate that hypertension is associated with mechanical systolic dysfunction, even in the presence of a normal ejection fraction, but whether this cardiac dysfunction may be ameliorated by antihypertensive treatment is unknown.
Methods:
To test the hypothesis that mechanical systolic dysfunction in hypertension may resp...
The Mobil-O-Graph (IEM, Stolberg, Germany) reports pulse wave velocities (PWV) and other hemodynamic variables as part of 24-hour ambulatory BP monitoring (ABPM). PWV is determined by a proprietary formula that includes “demographic information and pulse wave analysis”. The aim of this study was to identify the principal components of the IEM PWV a...
Background: Arterial stiffening in humans involves excess collagen deposition in large arteries and it has been theorized that arterial stiffness in humans is promoted by hyperaldosteronism. The aim of this reliminary survey study was to ascertain whether increased arterial stiffness could be demonstrated in individuals with life-long hyperaldoster...
Evaluate efficacy/safety of olmesartan medoxomil (OM)/amlodipine (AML)/ hydrochlorothiazide (HCTZ) in Hispanic/Latino adults with hypertension.
Randomized, double-blind, 12-week, parallel-group study followed by a 40-week open-label extension phase.
Clinical sites (317) in the United States and Puerto Rico.
Individuals > or =18 years of age with me...
Diastolic dysfunction is associated with adverse outcomes and is highly prevalent among older adults with hypertension. Lowering SBP with antihypertensive therapy has been shown to improve diastolic function, but whether or not age influences this effect is unknown.
In the Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic...
Aims
The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-d...
Hypertension is a complex, self-sustaining hemodynamic syndrome that is more closely associated with aging and acquired characteristics than genetic variation. Hypertension is not a discrete disease entity; it is simply an arbitrary fraction of the continuous Gaussian distribution of blood pressure (BP) in the general population. Critical anteceden...
Background:
Hypertension is often inadequately controlled in older people.
Objective:
This prespecified subgroup analysis assessed the efficacy and safety of an olmesartan medoxomil (OM) 40 mg/amlodipine besylate (AML) 10 mg/hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the 3 components as dual-combination treatment...
This chapter explains blood pressure variability and physiologic control of sympathetic nervous system (SNS) outflow. Control of SNS outflow is generated from complex bidirectional signals among interconnected centers within the central nervous system and peripheral tissues. Given the wide range of responses observed in normal human physiology, it...
Abstract Background Patients with hypertension and cardiovascular disease (CVD), diabetes, or chronic kidney disease (CKD) usually require two or more antihypertensive agents to achieve blood pressure (BP) goals. Methods The efficacy/safety of olmesartan (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg versus the co...
Guidelines recommend combining β-blockers and angiotensin-converting enzyme (ACE) inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit has not been determined. After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study in...
AimsTo investigate the effect of antihypertensive therapy on ventricular-arterial mechanics, coupling, and efficiency in early-stage hypertension.Methods and resultsWe studied 527 participants from two clinical trials assessing the effect of blood pressure lowering on diastolic function. Participants were aged ≥45 years with early-stage hypertensio...
Background: Guidelines recommend combining [beta]-blockers and ACE inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit however, has not been determined. Methods: After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study...
Background: Pulse wave velocity (PWV), a lumped arterial stiffness parameter, depends on arterial size and wall elastance, and is affected by aging and hypertension. Carotid-femoral (cf) PWV is commonly used but other PWV relationships to aging and hypertension are less well described. Methods: All subjects had supine Omron oscillometric blood pres...
Background: The systolic pulse contour at any point along the arterial tree is the sum of the forward- and backward-traveling pressure waves at that point. In the aorta, the first systolic pressure peak (P1, the forward wave) is augmented in late systole by the returning pressure wave (P2). In the arm, there is variable amplification of P1, and P2...
Background: It is widely believed that reflected pressure waves return in early diastole in younger people with elastic arteries and in late systole in older people with stiffer arteries. Methods: We studied a convenience sample of 229 men (42%) and women (58%) age 15-79 with systolic BP 87-212 mmHg. Each had radial tonometry (Sphygmocor) in the si...
Although awareness of hypertension in Black patients has increased, blood pressure (BP) is frequently inadequately controlled.
This prespecified subgroup analysis of the TRINITY study evaluated the efficacy and safety of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg triple-combination treatme...
Background
Although awareness of hypertension in Black patients has increased, blood pressure (BP) is frequently inadequately controlled.
Objective
This prespecified subgroup analysis of the TRINITY study evaluated the efficacy and safety of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg tripl...
Home blood pressure (BP) monitoring may enhance assessment of BP control. In this 16-week study, men and women 70 years or older with systolic BP between 150 and 200 mm Hg were randomized to receive valsartan/hydrochlorothiazide (V/HCTZ) 160/12.5 mg (n = 128), HCTZ 12.5 mg (n = 128), or V 160 mg (n = 128) for 4 weeks. Participants whose BP was 140/...
We have previously demonstrated in the Randomized Olmesartan and Diabetes Microalbuminuria Prevention study that the angiotensin receptor blocker (ARB) olmesartan delays the onset of microalbuminuria in patients with type 2 diabetes. Now, we investigated the effect in the subpopulation with hypertension.
Overall, 4020 patients with type 2 diabetes...
Background: Prior studies suggest that hypertension is associated with LA dysfunction, even in the presence of normal LA size; whether or not LA function can improve with BP lowering therapy is unknown.
J Clin Hypertens (Greenwich) . 2012;14:149–157. ©2012 Wiley Periodicals, Inc.
Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40‐week open‐label extension of the 12‐week double‐blind Tri ple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hyperte n s i ve Pati...
Renin profiling has been proposed as a method to guide antihypertensive drug selection. This prespecified post-hoc analysis examined the influence of baseline plasma renin activity (PRA) on blood pressure (BP) responses.
A 16-week, randomized, double-blind, prompted-titration trial evaluated initial valsartan (V)/hydrochlorothiazide (HCTZ) combinat...
There is little information about the hemodynamic and exercise-response implications of renin-angiotensin system blocker combinations. After a 3-week lisinopril (L; 40 mg/day) run-in, carvedilol (C; 20 then 40 mg/day) or valsartan (V; 160 then 320 mg/day) was added to L for 4 weeks each in a forced-titration, random order-entry crossover study in 3...
J Clin Hypertens (Greenwich). 2011;13:873–880. ©2011 Wiley Periodicals, Inc.
This 12-week, multicenter, randomized, double-blinded, 4-arm study in 440 patients with moderate to severe hypertension compared ambulatory blood pressure (ABP) responses with a triple-combination regimen (olmesartan medoxomil [OM] 40 mg, amlodipine besylate [AML] 10 mg, a...
Most patients with hypertension and diabetes require two or more antihypertensive agents to achieve the recommended blood pressure (BP) goal of <130/80 mm Hg. This prespecified subgroup analysis from the TRIple Therapy with Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in HyperteNsIve PatienTs StudY assessed the efficacy and safety of t...
J Clin Hypertens (Greenwich). 2011;13:722–730. ©2011 Wiley Periodicals, Inc.
This 16-week trial investigated the efficacy and safety of single-pill valsartan/hydrochlorothiazide (HCTZ) vs the individual components in patients 70 years and older with systolic hypertension. Patients were randomized to valsartan/HCTZ 160/12.5 mg (n=128), HCTZ 12.5 mg...
The renin-angiotensin system (RAS) is a common link between hypertension and comorbidities of obesity and metabolic syndrome (MetS). We evaluated the antihypertensive efficacy and safety of the combination direct renin inhibitor, aliskiren, with amlodipine versus amlodipine alone in self-identified African Americans with stage 2 hypertension in a s...
Our objective was to define the relationship between renal dysfunction--both albuminuria and reduced estimated glomerular filtration rate (eGFR)--and cardiac structure and diastolic dysfunction among patients with chronic hypertension.
Both albuminuria and eGFR were measured in 540 asymptomatic patients with hypertension and diastolic dysfunction a...
KEY POINTS AND RECOMMENDATIONS: • In addition to hypertension, angiotensin-converting enzyme inhibitors are indicated for treatment of patients at high risk for coronary artery disease, after myocardial infarction, with dilated cardiomypathy, or with chronic kidney disease. • The most familiar angiotensin-converting enzyme subtype, angiotensin-co...
Antihypertensive medications are used to lower blood pressure (BP) but, ultimately, their true value lies in reductions in morbidity and mortality (cardiovascular, cerebrovascular, and renal diseases). Hypertension is defined discreetly (generally 140/90 mmHg) but the actual relationship between BP and adverse cardiac and cerebrovascular outcomes i...
Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) is a useful tool for studying antihypertensive drugs and their combinations.
This multicenter, double-blind, parallel-group, prompted-titration study of patients of at least 70 years of age with systolic hypertension compared the ef...
J Clin Hypertens (Greenwich) . 2011;13:571–581. ©2011 Wiley Periodicals, Inc.
Initial multiple drug therapy for hypertension achieves greater and quicker reductions and higher blood pressure (BP) control rates than monotherapy. This 8‐week, prospective, multicenter, randomized, double‐blind study compared the efficacy and safety of the initial comb...
The New York State Medicaid Prescriber Education Program (PEP) is a partnership between the Department of Health and state academic institutions that provides prescribers with an evidence-based, noncommercial source of the latest objective information about pharmaceuticals. This article, detailing treatment of uncomplicated hypertension in diverse...
