Nadya Merchant

Metabolic syndrome and cardiovascular disease in South Asians

This review discusses the prevalence of metabolic syndrome and cardiovascular disease in the South Asian population, evaluates conventional and emerging risk factors, and reinforces the need for ethnic-specific redefinition of guidelines used to diagnose metabolic syndrome. We reviewed recent and past literature using Ovid Medline and PubMed databases. South Asians represent one of the largest and fastest growing ethnic groups in the world. With this growth, a dramatic rise in the rates of acute myocardial infarction and diabetes is being seen in this population. Potential etiologies for this phenomenon include dietary westernization, poor lifestyle measures, adverse body fat patterning, and genetics. While traditional risk factors for diabetes and cardiovascular disease should not be overlooked, early metabolic syndrome has now been shown in the South Asian pediatric population, suggesting that “metabolic programming” and perinatal influences may likely play a substantial role. Health care practitioners must be aware that current guidelines used to identify individuals with metabolic syndrome are underestimating South Asian individuals at risk. New ethnic-specific guidelines and prevention strategies are discussed in this review and should be applied by clinicians to their South Asian patients.

Usefulness of elevations in serum choline and free F2)-isoprostane to predict 30-day cardiovascular outcomes in patients with acute coronary syndrome.

Our objectives were to evaluate the prognostic value of several biomarkers in patients with acute coronary syndrome (ACS) through an evaluation of the 30-day clinical outcomes. Multiple biomarkers have emerged as potentially useful in risk stratification of ACS. Specifically, markers of vascular inflammation and oxidative stress might be helpful in the determination of clinical outcomes. We evaluated patients presenting with chest pain. ACS was defined by symptoms of cardiac ischemia plus electrocardiographic changes or positive troponin I. Levels of serum troponin I, high sensitivity C-reactive protein, serum choline, and free F(2)-isoprostane were obtained. Patients were followed up for 30 days (n = 108) with determination of nonfatal myocardial infarction, congestive heart failure, need for revascularization, and death. Of the 108 patients, 26 had a cardiac event. Free F(2)-isoprostane and choline levels (but not high-sensitivity C-reactive protein levels) predicted 30-day cardiac events. To determine the value of choline and F(2)-isoprostane levels in predicting 30-day cardiac events, receiver operating curves were generated. The optimal cutoff point of these markers was a serum F(2)-isoprostane level of 124.5 pg/ml (r = 0.82) and a serum choline level of 30.5 mumol/L (r = 0.76). F(2)-isoprostane and choline had a positive predictive value of 57% and 44% and a negative predictive value of 90% and 89%, respectively. In conclusion, serum choline and free F(2)-isoprostane are predictors of cardiac events in ACS. A model that includes an array of biomarkers, including troponin, choline, and free F(2)-isoprostane, might be useful in predicting patients at greater risk of future events in ACS.

Raising HDL cholesterol in women.

High-density lipoprotein cholesterol (HDL-C) concentration is essential in the determination of coronary heart disease (CHD) risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.

The impact of lipoic acid on endothelial function and proteinuria in quinapril-treated diabetic patients with stage I hypertension: results from the QUALITY study.

Background: We sought to determine whether a combination of angiotensin-converting enzyme inhibitors (ACEIs) and the nutraceutical α-lipoic acid (ALA) regulates blood pressure, endothelial function, and proteinuria in diabetic patients with Stage I hypertension. Methods: A total of 40 diabetic patients with Stage I hypertension were treated in a crossover double-blinded manner. Patients were administered quinapril ([QUI] 40 mg/d) for 8 weeks or QUI + ALA (600 mg/d) for 8 weeks. Measurements included blood pressure, 24-hour collection of urinary albumin, and endothelial-dependent flow-mediated dilation (FMD). Results: There was a change of metabolic parameters in both study groups after 8 weeks of therapy. In comparison to baseline, the 24-hour urinary albumin significantly decreased by 30% in the QUI group (P = .018, time comparison) and 53% in QUI + ALA group (P < .005, time and group comparison). Also, when compared with baseline, FMD significantly increased by 58% in QUI group (P < .005, time comparison) and by 116% in QUI + ALA group (P < .005, time and group comparison). Systolic and diastolic blood pressure reduced significantly by 10% with QUI treatment. There was no further blood pressure reduction when patients were administered both QUI and ALA. Conclusions: In diabetic patients with hypertension, QUI reduces blood pressure, proteinuria, and improves endothelial function. Moreover, this effect is strongly potentiated with a combination of QUI and ALA. These results may attenuate the progression of vascular pathophysiology seen in patients with a combination of diabetes and hypertension.

Pretreatment with n-6 PUFA protects against subsequent high fat diet induced atherosclerosis-Potential role of oxidative stress-induced antioxidant defense

OBJECTIVES Recent evidence suggests that oxidative stress can promote antioxidant defense and thus be athero-protective. n-6 polyunsaturated fatty acids (n-6 PUFA) are more prone to oxidation, compared to monounsaturated fatty acids (MUFA) and yet have proven anti-atherosclerotic effects. In this study, we tested whether early exposure to a diet rich in n-6 PUFA, compared to a MUFA rich diet would reduce lesion burden, even with subsequent exposure to a high fat, high cholesterol diet (HF). Further, we tested to determine whether oxidative mechanisms are involved in such protection. METHODS AND RESULTS Twenty four, 4 week old, male, LDL receptor knockout (LDL-R(-/-)) mice were divided into two groups and fed either a n-6 PUFA rich or a MUFA rich diet for a period of 12 weeks. At this point, 4 mice from each group were euthanized and the remaining 8 mice from each group were fed a HF diet for four weeks. Atherosclerotic lesions, plasma lipids, autoantibodies to lipid peroxide modified proteins, isoprostanes and aortic catalase levels were measured. The n-6 PUFA diet reduced aortic lesions and plasma lipids compared to the MUFA diet and this reduction in lesions continued even after the mice were switched over to the HF diet, despite the fact that the plasma lipids were similar in both groups after the HF diet. n-6 PUFA fed mice had highest plasma isoprostane levels, indicating oxidative stress, but also had higher levels of aortic catalase. On the other hand, MUFA fed mice had comparatively lower levels of isoprostanes and their aortic catalase levels remained low. Finally, aortic lesions were negatively correlated with isoprostanes and catalase. CONCLUSION An initial exposure to a n-6 PUFA rich diet compared to a MUFA rich diet reduces atherosclerotic lesions and this protection probably involves oxidative stress induced by PUFA.

Nebivolol in High-Risk, Obese African Americans With Stage 1 Hypertension: Effects on Blood Pressure, Vascular Compliance, and Endothelial Function

The authors sought to determine whether nebivolol treatment results in changes in blood pressure (BP), nitric oxide bioavailability, and vascular function in obese African Americans with recently diagnosed stage 1 hypertension. Forty‐three obese, hypertensive African Americans (mean BP: systolic, 148.8±14.3 mm Hg; diastolic, 90.4±8.2 mm Hg) were treated with nebivolol (5–10 mg/d) for 8 weeks. Primary outcomes were change in systolic and diastolic BP and efficacy in reaching normotensive BP. Mean systolic BP decreased by 9.2±14 mm Hg (P<.005) and diastolic BP decreased 6.8±9 mm Hg (P<.005) with 8 weeks of therapy. Significant improvements were seen in arterial compliance with nebivolol treatment as measured by aortic augmentation index (P<.005) and time to wave reflection (P=.013). Nebivolol treatment improved endothelial function as measured by flow‐mediated dilation (P<.005). Levels of erythrocyte cellular superoxide dismutase increased with nebivolol, indirectly suggesting increased bioavailability of nitric oxide (P<.005). Monotherapy with nebivolol in obese, hypertensive African Americans results in significant systolic and diastolic BP reduction by mechanisms that include improved vascular function and compliance.

Vascular Effects of Nebivolol Added to Hydrochlorothiazide in African Americans With Hypertension and Echocardiographic Evidence of Diastolic Dysfunction The NASAA Study

Background: African Americans have greater risk of cardiovascular events than comparator populations of white European origin. A potential reason for this is reduced nitric oxide bioavailability in African Americans, resulting in increased prevalence of factors that contribute to ventricular dysfunction. We investigated the effects of nebivolol with the diuretic hydrochlorothiazide (HCTZ) in hypertensive African Americans with echocardiographic evidence of diastolic dysfunction. Methods: A total of 42 African American patients were assigned to nebivolol and HCTZ in an open-label fashion for a 24-week period. Changes in blood pressure (BP), echocardiographic parameters, and success in attaining target BP were determined. As an indirect determinant of endothelial function, serum total nitric oxide (NOx) levels and asymmetric dimethyl arginine (ADMA) levels were performed at baseline and after the treatment period. Results: The systolic BP decreased from 150 ± 13 to 136 ± 16 mm Hg (P < .005). Diastolic BP decreased from 94 ± 13 to 84 ± 9 mm Hg (P = .008). Of the patients that completed the study, 77% achieved a combined target BP of systolic BP <140 mm Hg and a diastolic BP <90 mm Hg. Serum NOx increased by 41% and 39% in patients that were treated with 10 mg and 20 mg daily nebivolol, respectively. The ADMA levels decreased by 44% following treatment. The change in systolic BP was strongly correlated to the change in ADMA (r = .54; P = .024). Furthermore, in comparison to a group of age-matched patients controlled with diuretic therapy only, the ADMA levels were significantly lower in the nebivolol posttreatment group (controlled BP with diuretic: 0.32 ± 0.07μmol/L; nebivolol posttreatment: 0.24 ± 0.06 μmol/L; P < .05). Conclusion: Reduced BP with nebivolol in hypertensive African Americans and echocardiographic evidence of diastolic dysfunction correlates with improved endothelial function. Furthermore, improvement in endothelial function and increased nitric oxide bioavailability suggests a potential mechanism of efficacy of nebivolol in these patients.

Changes in Central Aortic Pressure, Endothelial Function and Biomarkers in Hypertensive African-Americans with the Cardiometabolic Syndrome: Comparison of Amlodipine/Olmesartan versus Hydrochlorothiazide/Losartan

Sixty-six self-identified African-American subjects with stage 1 and 2 hypertension and characteristics of the cardiometabolic syndrome were treated with amlodipine/olmesartan (A/O) versus losartan/hydrochlorothiazide (L/H) for 20 weeks in an open-label, active comparator fashion. Subjects not meeting a blood pressure (BP) value of <125/75 mm Hg on either regimen at week 14 were placed on additional or alternative therapy. After 20 weeks of therapy, systolic BP was reduced by 34.6 ± 4.2 mm Hg in the A/O group and by 27.0 ± 4.1 mm Hg in the L/H group (p = 0.012 A/O vs. L/H). Diastolic BP was reduced by 16.9 ± 2.0 mm Hg in the A/O group and by 12.3 ± 2.0 mm Hg in the L/H group (p = 0.022 A/O vs. L/H). There was a substantial increase in endothelial function of 44 and 103% in the L/H and A/O groups, respectively (p < 0.005 A/O vs. L/H). Central aorta augmentation pressure was significantly reduced by 42% with the A/O treatment, and a smaller, significant reduction of 28% was observed with the L/H treatment (p = 0.034 A/O vs. L/H). There was a reduction in sIL-6 levels of 20 and 33%, a reduction in serum leptin levels of 22 and 40%, and an increase in serum adiponectin of 19 and 46% in the L/H and A/O groups, respectively (p < 0.005 A/O vs. L/H for each biomarker). Treatment with A/O after 14 weeks reduced pulse wave velocity by 22% (p = 0.011 time comparison), whereas L/H treatment had no significant effect. Our findings suggest that, in addition to effective BP reduction, A/O differentially regulates markers of inflammation and obesity, thereby potentially providing greater vascular protection.

Contents Vol. 3, 2013

S. Brietzke, Columbia, Mo. M. Bursztyn, Jerusalem K.C. Dellsperger, Augusta, Ga. V. DeMarco, Columbia, Mo. J.P. Dwyer, Nashville, Tenn. K.C. Ferdinand, New Orleans, La. J.M. Flack, Detroit, Mich. E.P. Gomez-Sanchez, Jackson, Miss. M.R. Hayden, Camdenton, Mo. E.J. Henriksen, Tucson, Ariz. J.M. Luther, Nashville, Tenn. F. Murad, Washington, D.C. C. Ronco, Vicenza N. Stern, Tel Aviv C.S. Stump, Tucson, Ariz. A.T. Whaley-Connell, Columbia, Mo. Founded 2011 by J.R. Sowers CardioRenal Medicine

The Effects of Antihypertensive Agents in Metabolic Syndrome – Benefits Beyond Blood Pressure Control

© 2012 Merchant and Khan, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Effects of Antihypertensive Agents in Metabolic Syndrome – Benefits Beyond Blood Pressure Control