Howard Weintraub, M.D.

Effect of valsartan, hydrochlorothiazide, and their combination on 24-h ambulatory blood pressure response in elderly patients with systolic hypertension: a ValVET substudy
Duprez, Daniel A; Weintraub, Howard S; Cushman, William C; Purkayastha, Das; Zappe, Dion; Samuel, Rita; Izzo, Joseph L Jr
2011 Aug;16(4):186-196, Blood pressure monitoring
BACKGROUND: Stage 2 hypertension often requires combination antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) is a useful tool for studying antihypertensive drugs and their combinations. OBJECTIVE: This multicenter, double-blind, parallel-group, prompted-titration study of patients of at least 70 years of age with systolic hypertension compared the efficacy of valsartan, hydrochlorothiazide, and their combination on ambulatory blood pressure (ABP) reduction. METHODS: After a 3-14-day washout, patients with systolic blood pressure of 150-200 mmHg were randomized (1 : 1 : 1) to initially receive once-daily valsartan/hydrochlorothiazide 160/12.5 mg combination therapy, hydrochlorothiazide 12.5 mg monotherapy, or valsartan 160 mg monotherapy. Prompted uptitration of patients in whom BP was more than or equal to 140/90 mmHg was performed after 4, 8, and 12 weeks of treatment. ABPM was performed at baseline and weeks 4 and 16 (study end). RESULTS: In this ABPM substudy (n=108), initiation of treatment with valsartan/hydrochlorothiazide lowered ABP more effectively than either monotherapy throughout the daytime, night-time, and 24-h monitoring periods, as well as during the last 4 and 6-h dosing periods. Twenty-four-hour ABP was reduced from 141.1/76.5 mmHg at baseline to 125.8/69.2 mmHg at week 4 (primary time point) with valsartan/hydrochlorothiazide compared with reductions from 142.2/78.7 to 139.1/77.5 mmHg with hydrochlorothiazide and 142.2/78.3 to 136.4/75.1 mmHg with valsartan (all P<0.01 in favor of combination therapy). In the overall study, tolerability was similar among the three treatment groups. CONCLUSION: In elderly hypertensives, starting combination therapy with valsartan/hydrochlorothiazide provides more effective 24-h blood pressure control than the monotherapy components, with few therapy-related side-effects
— id: 136493, year: 2011, vol: 16, page: 186, stat: Journal Article,

Treating Systolic Hypertension in the Very Elderly With Valsartan-Hydrochlorothiazide vs Either Monotherapy: ValVET Primary Results
Izzo, Joseph L Jr; Weintraub, Howard S; Duprez, Daniel A; Purkayastha, Das; Zappe, Dion; Samuel, Rita; Cushman, William C
2011 Oct;13(10):722-730, Journal of clinical hypertension
J Clin Hypertens (Greenwich). 2011;13:722-730. (c)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 (n=128), or valsartan 160 mg (n=128) for 4 weeks. Patients whose blood pressure (BP) was >/=140/90 mm Hg at weeks 4, 8, or 12 were up-titrated to a maximum of valsartan/HCTZ 320/25 mg. Week 4 systolic BP reduction (primary efficacy outcome) was greater with valsartan/HCTZ than valsartan (-17.3 mm Hg vs -8.6 mm Hg, P <.0001) but only marginally greater than HCTZ (-13.6 mm Hg, P =.096). Median time to BP control was shorter with valsartan/HCTZ (4 weeks) vs HCTZ (8 weeks, P<.05) or valsartan (12 weeks, P<.0001). Thiazide monotherapy was more effective than angiotensin receptor blocker monotherapy (by about 5 mm Hg), but greater antihypertensive efficacy was achieved by initiating treatment with combination valsartan/HCTZ in the elderly
— id: 138118, year: 2011, vol: 13, page: 722, stat: Journal Article,

Role of RAAS Inhibition in the Prevention of Cardiovascular Disease
Tran, Henry A; Schwartzbard, Arthur; Weintraub, Howard S
2011 Aug;13(4):279-288, Current treatment options in cardiovascular medicine
OPINION STATEMENT: The pathogenesis of cardiovascular disease is a complex and dynamic process. The renin-angiotensin-aldosterone system (RAAS) is a potent and powerful mediator in the homeostasis of the cardiovascular and renal systems. RAAS blockade via angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) has been consistently proven to be an effective and safe strategy for the primary and secondary prevention of cardiovascular disease in patients across a wide spectrum of risk. Although the beneficial effects of RAAS blockade may be due to its effects on central and peripheral blood pressure, there are many additional mechanisms to consider that may contribute additional protection. While a combination of ACE inhibitors and ARBs has not yielded significantly positive results, the newer class of direct renin inhibitors (DRIs) may offer a novel and effective strategy for monotherapy as well as in combination
— id: 135256, year: 2011, vol: 13, page: 279, stat: Journal Article,

Combination Therapy for Managing Difficult-to-Treat Patients With Stage 2 Hypertension: Focus on Valsartan-Based Combinations
Weintraub, Howard S; Rudolph, Amy
2011 Nov;18(6):e227-e243, American journal of therapeutics
Blood pressure (BP) control rates in the United States remain low despite the availability of a wide array of treatment options. High-risk populations, including women, black individuals, and obese patients are even less likely to achieve BP targets than the general population. Uncontrolled BP can lead to serious consequences. Therefore, additional effective and well-tolerated treatment strategies are necessary, particularly for these difficult-to-treat populations. The majority of patients require 2 or more pharmacologic agents to achieve BP control. In patients with stage 2 hypertension, current guidelines recommend rational antihypertensive combinations as initial therapy. The renin-angiotensin-aldosterone system (RAAS) plays an important role in development of hypertension and progression, and the use of RAAS inhibitors has shown BP-lowering effectiveness and excellent tolerability across a continuum of patient types. Agents that block the RAAS form a reasonable foundation for combination therapy. In this article, we review data from studies of valsartan-based antihypertensive combinations in stage 2 hypertension, with a focus on women, black individuals, and obese patients
— id: 141066, year: 2011, vol: 18, page: e227, stat: Journal Article,

Potential benefits of aliskiren beyond blood pressure reduction
Weintraub, Howard S; Tran, Henry; Schwartzbard, Arthur
2011 Mar-Apr;19(2):90-94, Cardiology in review
There is now clear evidence that reducing blood pressure (BP) with a broad range of agents, including angiotensin converting enzyme inhibitors and angiotensin receptor blockers, improves cardiovascular and renal outcomes. There is also evidence suggesting that these drugs have beneficial effects that are independent of BP lowering. Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step. Unlike angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, aliskiren produces a sustained reduction in plasma renin activity and reduces plasma levels of angiotensin II and aldosterone. Preclinical data and clinical trials in high-risk patients using surrogate markers increasingly suggest that aliskiren can reduce the progression of end-organ damage beyond that afforded by BP control. With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits. Evaluation of these end-organ effects in humans is underway in clinical trials designed to assess the effects of aliskiren alone and in combination with other antihypertensive agents on cardiovascular and renal outcomes
— id: 122546, year: 2011, vol: 19, page: 90, stat: Journal Article,

HOME AND CLINIC BP RESPONSES IN ELDERLY INDIVIDUALS WITH SYSTOLIC HYPERTENSION DURING INITIAL TREATMENT WITH COMBINED ANGIOTENSIN RECEPTOR BLOCKER plus DIURETIC COMPARED TO MONOTHERAPY
Cushman, W.; Duprez, D.; Weintraub, H.; Samuel, R.; Purkayastha, D.; Zappe, D.; Izzo, J. L.
2010 JUN ;28(49):-, Journal of hypertension
— id: 117298, year: 2010, vol: 28, page: , stat: Journal Article,

EFFECT OF VALSARTAN, HYDROCHLOROTHIAZIDE, AND ITS COMBINATION ON 24-HOUR AMBULATORY BLOOD PRESSURE RESPONSE IN ELDERLY INDIVIDUALS WITH SYSTOLIC HYPERTENSION: A VALVET SUBSTUDY
Duprez, D.; Weintraub, H.; Samuel, R.; Purkayastha, D.; Zappe, D.; Cushman, W.; Izzo, J. L.
2010 JUN ;28(49):E476-E476, Journal of hypertension
— id: 117301, year: 2010, vol: 28, page: E476, stat: Journal Article,

INITIAL COMBINED VALSARTAN/HCTZ THERAPY VS EITHER COMPONENT AS MONOTHERAPY IN ELDERLY INDIVIDUALS WITH SYSTOLIC HYPERTENSION: AGE-STRATIFIED ANALYSIS OF THE VALVET STUDY
Izzo, J. L.; Duprez, D.; Weintraub, H.; Samuel, R.; Purkayastha, D.; Zappe, D.; Cushman, W.
2010 JUN ;28(49):E473-E473, Journal of hypertension
— id: 117299, year: 2010, vol: 28, page: E473, stat: Journal Article,

EFFICACY AND TOLERABILITY OF COMBINED ANGIOTENSIN RECEPTOR BLOCKER plus DIURETIC THERAPY VS COMPONENT MONOTHERAPIES IN ELDERLY INDIVIDUALS WITH SYSTOLIC HYPERTENSION: RESULTS FROM VALVET
Izzo, J. L.; Weintraub, H.; Duprez, D.; Samuel, R.; Purkayastha, D.; Zappe, D.; Cushman, W.
2010 JUN ;28(49):E475-E475, Journal of hypertension
— id: 117300, year: 2010, vol: 28, page: E475, stat: Journal Article,

Ranolazine: a new approach to treating an old problem
Reddy, Bharath M; Weintraub, Howard S; Schwartzbard, Arthur Z
2010 ;37(6):641-647, Texas Heart Institute journal
Chronic angina pectoris affects millions of patients every year. During the past 2 decades, advances in medical therapy have led to substantial reductions in the symptoms of angina. Nonetheless, many patients continue to experience persistent angina that causes debilitating symptoms and lifestyle changes. Moreover, many current therapeutic agents cause side effects that can induce substantial morbidity on their own. In major clinical trials, the drug ranolazine has been shown to bring symptomatic relief to large numbers of patients who have chronic angina. Herein, we review the physiology of the sodium channel; the pharmacology of ranolazine; clinical trials that support use of the drug; recent evidence about ranolazine's therapeutic effect on diastolic heart failure, glycemic control, and atrial fibrillation and other arrhythmias; officially approved clinical indications; and avenues of future study
— id: 119239, year: 2010, vol: 37, page: 641, stat: Journal Article,

Fish oil for the treatment of cardiovascular disease
Weitz, Daniel; Weintraub, Howard; Fisher, Edward; Schwartzbard, Arthur Z
2010 Sep-Oct;18(5):258-263, Cardiology in review
Omega-3 fatty acids, which are found abundantly in fish oil, are increasingly being used in the management of cardiovascular disease. It is clear that fish oil, in clinically used doses (typically 4 g/d of eicosapentaenoic acid and docosahexaenoic acid) reduce high triglycerides. However, the role of omega-3 fatty acids in reducing mortality, sudden death, arrhythmias, myocardial infarction, and heart failure has not yet been established. This review will focus on the current clinical uses of fish oil and provide an update on their effects on triglycerides, coronary artery disease, heart failure, and arrhythmia. We will explore the dietary sources of fish oil as compared with drug therapy, and discuss the use of fish oil products in combination with other commonly used lipid-lowering agents. We will examine the underlying mechanism of fish oil's action on triglyceride reduction, plaque stability, and effect in diabetes, and review the newly discovered anti-inflammatory effects of fish oil. Finally, we will examine the limitations of current data and suggest recommendations for fish oil use
— id: 111598, year: 2010, vol: 18, page: 258, stat: Journal Article,

Consensus panel recommendation for incorporating lipoprotein-associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines
Davidson, Michael H; Corson, Marshall A; Alberts, Mark J; Anderson, Jeffrey L; Gorelick, Philip B; Jones, Peter H; Lerman, Amir; McConnell, Joseph P; Weintraub, Howard S
2008 Jun 16;101(12A):51F-57F, American journal of cardiology
A consensus panel was formed to review the rapidly emerging literature on the vascular-specific inflammatory marker lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and to update recommendations for the appropriate use of this novel biomarker in clinical practice. The recommendations of the panel build on guidelines of the Adult Treatment Panel III (ATP III) and the American Heart Association/Centers for Disease Control (AHA/CDC) for cardiovascular risk assessment. Consistent with the ATP III guideline recommendations for the use of inflammatory markers, Lp-PLA(2) is recommended as an adjunct to traditional risk assessment in patients at moderate and high 10-year risk. A simplified framework for traditional Framingham risk factor assessment is proposed. As a highly specific biomarker for vascular inflammation, elevated Lp-PLA(2) levels should prompt consideration of increasing the cardiovascular risk category from moderate to high or high to very high risk, respectively. Because intensification of lifestyle changes and low-density lipoprotein (LDL) cholesterol lowering is beneficial in high-risk patients, regardless of baseline LDL cholesterol levels, consideration should be given to lowering the LDL cholesterol target by 30 mg/dL (1 mg/dL = 0.02586 mmol/L) in patients with high levels of Lp-PLA(2). Lp-PLA(2) is recommended as a diagnostic test for vascular inflammation to better identify patients at high or very high risk who will benefit from intensification of lipid-modifying therapies. However, at this time Lp-PLA(2) cannot be recommended as a target of therapy
— id: 94263, year: 2008, vol: 101, page: 51F, stat: Journal Article,

Fibrate therapy: an update
Remick, Joshua; Weintraub, Howard; Setton, Robert; Offenbacher, Joseph; Fisher, Edward; Schwartzbard, Arthur
2008 May-Jun;16(3):129-141, Cardiology in review
Fibrates are a class of lipid-lowering medication primarily used as second-line agents behind statins. Acting via the peroxisome proliferators-activated receptor-alpha, their main lipoprotein effects are to lower serum triglyceride levels and to raise high-density lipoprotein-cholesterol, with modest effects on low-density lipoprotein-cholesterol. However, many clinical trials indicate that fibrates may have benefits beyond simply altering one's lipid profile. Several angiographic studies show retardation in the progression of atherosclerotic lesions in coronary vessels. Although clinical trials have failed to show a reduction in mortality with fibrates, several post hoc analyses indicate that there may be a mortality benefit in patients with features of the metabolic syndrome. Given that fibrates are often used as second-line agents, it is essential they are safe to be given in combination with other agents, particularly statins and ezetimibe. Although the side-effect profile of fibrates includes gastrointestinal symptoms, increased liver function tests, a reversible rise in creatinine and myositis, in general, fibrates seem to be safe to use in combination with other lipid lowering medications. Thus far, fibrates have not shown a mortality benefit in randomized clinical trials; as a result, they cannot be considered first-line medication for the primary or secondary prevention of coronary artery disease
— id: 79383, year: 2008, vol: 16, page: 129, stat: Journal Article,

Identifying the vulnerable patient with rupture-prone plaque
Weintraub, Howard S
2008 Jun 16;101(12A):3F-10F, American journal of cardiology
Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality in the United States, and the obesity epidemic combined with aging of the population seems destined to increase the burden of this disease. Traditional cardiovascular risk assessment accounts for <50% of the variability in risk in the United States. Therefore, better and more effective identification of persons at high cardiovascular risk is needed. Our understanding of atherosclerosis has shifted from a focal disease whose hallmark is symptoms caused by a severe stenosis to a systemic disease characterized by endothelial dysfunction (ED) and plaque inflammation, with the potential for rupture and thrombosis mainly in those with subcritical stenosis. Under the new paradigm, clinicians require updated strategies to better assess the quality of arterial plaque. Effective tools for primary and secondary prevention of heart attack and stroke include intensive lifestyle modification, blood pressure reduction, and lipid-modifying therapies. These interventions are now understood to decrease plaque inflammation and thereby promote plaque stability. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) appears to be a specific marker of plaque inflammation that may play a direct role in the formation of rupture-prone plaque. In contrast, traditional risk factors, lipid measurement, and most vascular imaging modalities do not directly assess the acute ischemic potential in the arterial wall. Measuring Lp-PLA(2) levels in human serum or plasma is noninvasive and relatively inexpensive. Lp-PLA(2) may provide additional clinically relevant information that shows which patients have a high level of atherosclerotic disease activity as manifested by vascular inflammation, ED, and increased risk for progression toward rupture-prone plaque
— id: 81573, year: 2008, vol: 101, page: 3F, stat: Journal Article,

The Pleiotropic Effects of Antihypertensive Agents: Do They Account for Additional Cardiovascular Benefit Beyond BP Reduction?
Weintraub, Howard S; Basile, Jan
2008 Aug;101(8):818-823, Southern medical journal
Hypertension commonly clusters with other cardiovascular risk factors, giving rise to the concept that hypertension is a multifaceted disease that potentially shares common pathogenic pathways with other risk factors. The renin-angiotensin-aldosterone system has a central role in the shared mechanisms of hypertension and cardiovascular disease, primarily through angiotensin II. Increased levels of angiotensin II disrupt the balance of vasoactive substances and growth factors that regulate endothelial structure and function, and inhibition of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker helps restore this equilibrium. Some pathogenic mechanisms may also be favorably affected by calcium channel blockade. While the relative contribution of pleiotropic effects to clinical benefit is difficult to quantify, based on recent data it is reasonable to consider using newer antihypertensive agents in selected high-risk patients to realize the benefits that may derive from interfering with pathogenic mechanisms of disease
— id: 94264, year: 2008, vol: 101, page: 818, stat: Journal Article,

Treatment of multiple-risk patients: using combination therapy to treat beyond LDL lowering
Weintraub, Howard S
2005 Aug;7(4):265-270, Current hypertension reports
During the past 25 years, the role of traditional 'risk factors' in the genesis of atherosclerotic vascular disease has been convincingly validated. The impact of elevated low-density lipoprotein cholesterol, hypertension, type II diabetes, and metabolic syndrome are now well accepted. However, until recently, there was guilt by association without a clear understanding of the manner in which the crime was committed. It is now acknowledged that the presence of multiple risk factors can increase the likelihood of an ischemic event. This has become a great concern, given the very high prevalence of patients who fall into this category. In light of this information, the mandate for appropriate guideline-driven therapy has become even stronger, and we must consider the use of multiple medications to effectively neutralize this risk
— id: 61419, year: 2005, vol: 7, page: 265, stat: Journal Article,

Torsades de pointes, a potential complication of diuretic-induced hypokalemia and hypomagnesemia in patients with congestive heart failure: Conference presentation of a generic patient
Cohen, JD; Blumenthal, R; Horn, HR; Weintraub, H; Weglicki, W
2002 DEC ;63(12):803-809, Current therapeutic research
Background: Despite improvements in care, the prognosis for patients with congestive heart failure (CHF) remains poor. Fifty percent of patients with CHF suffer from arrhythmia and sudden cardiac death. This may be attributable in part to the use of medications that contribute to electrolyte imbalance. Objective: This article presents a case report of a woman with CHF due to left ventricular systolic dysfunction. Results: The case report involved a 52-year-old white woman with a history of paroxysmal atrial fibrillation, atypical chest pain, and dyslipidemia. Her medical treatment had included the use of furosemide (a loop diuretic), digoxin, and sotalol; she subsequently developed torsades de pointes (TdP). An electrocardiogram showed normal sinus rhythm; the QT(c) interval was 530 msec. Levels of digoxin, K+, and Mg2+ were 1.8 ng/mL, 3.5 mEq/L, and 1.5 mEq/L, respectively. Results of a Holter monitor recording suggested that the hypomagnesemia and hypokalemia, interacting with the digoxin and sotalol, potentiated the development of a prolonged QT interval. To ensure the TdP did not recur, an IV bolus of Mg2+ was administered and oral triamterene therapy was added to the patient's current medications. These additions appeared to correct the electrolyte imbalance. Conclusion: This case exemplifies the importance of recognizing and managing electrolyte imbalance in the treatment of patients with CHF
— id: 55593, year: 2002, vol: 63, page: 803, stat: Journal Article,

Tools for stratifying stroke risk
Weintraub HS
2001 ;18(9):15-16, Cardiology review
— id: 26876, year: 2001, vol: 18, page: 15, stat: Journal Article,

The case for ace inhibition
Weintraub HS
2000 ;17(4):37-37, Cardiology review
— id: 15943, year: 2000, vol: 17, page: 37, stat: Journal Article,

Role of inflammatory mediators
Weintraub HS
1999 ;16(10):39-39, Cardiology review
— id: 15951, year: 1999, vol: 16, page: 39, stat: Journal Article,

MYOD FORMS MICELLES WHICH CAN DISSOCIATE TO FORM HETERODIMERS WITH E47 - IMPLICATIONS OF MICELLIZATION ON FUNCTION
LAUE, TM; STAROVASNIK, MA; WEINTRAUB, H; SUN, XH; SNIDER, L; KLEVIT, RE
1995 DEC 5 ;92(25):11824-11828, Proceedings of the National Academy of Sciences of the United States of America
MyoD is a member of a family of DNA-binding transcription factors that contain a helix-loop-helix (HLH) region involved in protein-protein interactions, In addition to self-association and DNA binding, MyoD associates with a number of other HLH-containing proteins, thereby modulating the strength and specificity of its DNA binding, Here, we examine the interactions of full-length MyoD with itself and with an HLH-containing peptide portion of an E2A gene product, E47-96. Analytical ultracentrifugation reveals that MyoD forms micelles that contain more than 100 monomers and are asymmetric and stable up to 36 degrees C, The critical micelle concentration increases slightly with temperature, but micelle size is unaffected, The micelles are in reversible equilibrium with monomer, Addition of E47-96 results in the stoichiometric formation of stable MyoD-E47-96 heterodimers and the depletion of micelles, Micelle formation effectively holds the concentration of free MyoD constant and equal to the critical micelle concentration, In the presence of micelles, the extent of all interactions involving free MyoD is independent of the total MyoD concentration and independent of one another, For DNA binding, the apparent relative specificity for different sites can be affected. In general, heterodimer-associated activities will depend on the self-association behavior of the partner protein
— id: 52660, year: 1995, vol: 92, page: 11824, stat: Journal Article,

Myelofibrosis associated with migratory polyarthritis and serositis
Agus B; Weintraub HS
1986 Apr;13(2):476-477, Journal of rheumatology
— id: 63510, year: 1986, vol: 13, page: 476, stat: Journal Article,

KILLING MEDICINE
GOREN, EN; WAXMAN, SG; PISETSKY, DS; LEVIN, MH; NOVICK, I; WEINTRAUB, H; SCHWARTZ, ML; MAJOR, F; OLSCHANSKY, KV; GORDON, D; MILLEY, JR
1969 ;161(2866):40-40, New Republic
— id: 39764, year: 1969, vol: 161, page: 40, stat: Journal Article,