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We evaluated the efficacy of amlodipine and olmesartan (A/O; Azor) versus losartan and hydrochlorothiazide (L/H; Hyzaar), on changes in serum and urine biomarkers of inflammation and oxidation, neutrophil reactive oxygen species generation, and changes in systolic blood pressure (BP), diastolic BP, and heart rate as measured with 24 hours ambulatory BP monitoring in a high-risk, hypertensive African-American population with the metabolic syndrome. Sixty-six African-American subjects with Stage 1 and 2 hypertension and characteristics of the metabolic syndrome were treated in open-label, active comparator fashion for 20 weeks. After 14 weeks of therapy, treatment with A/O had a significant effect on reducing the production of reactive oxygen series, plasminogen activator inhibitor-1, F2 isoprostane, myeloperoxidase, and homeostasis model assessment for insulin resistance while L/H treatment only significantly lowered levels of plasminogen activator inhibitor-1 and homeostasis model assessment for insulin resistance. Treatment with A/O showed a trend of a more immediate and sustained systolic and diastolic BP-lowering, as well as night time BP reduction. In addition to a trend toward lower blood pressure, treatment with A/O in comparison with L/H has superior efficacy in reducing reactive oxygen species generation and production of inflammatory and oxidative biomarkers in a hypertensive African-American population with features of the metabolic syndrome., (Copyright © 2013 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Traditional risk factor assessments for coronary heart disease (CHD) often fail to take into account individual factors such as race and lipid profiles that may substantially elevate a patient's risk for CHD or a cardiovascular event. Although numerous treatment guidelines have been issued on metabolic syndrome, discrepancies among the guidelines can create confusion. Cardiac biomarkers and imaging methods have emerged to help detect and quantify subclinical atherosclerosis, but many of these are not proven as cost-effective for use in clinical practice or for routine screening. As the present case-based activity demonstrates, determining appropriate diagnostic and management strategies according to CHD risk is a process that challenges physicians to consider myriad individual patient variables.

African Americans with diabetes +/- the metabolic syndrome are at high risk for cardiovascular disease. This subanalysis of the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE) trial studied attainment of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) goals by 8 flexibly titrated doses (5/10-10/80 mg) of amlodipine/atorvastatin single pill in 494 African Americans with hypertension and dyslipidemia, according to the presence of diabetes +/- the metabolic syndrome. In 169 diabetic patients, the metabolic syndrome was associated with poorer BP goal attainment (38.5% vs 48.5% in diabetic patients without the metabolic syndrome). Among diabetic patients (+/- the metabolic syndrome) 61% to 62% reached LDL-C goal. More than 60% of patients with diabetes uncontrolled for LDL-C were maintained on suboptimal atorvastatin therapy (mean final dose: 29.9 mg vs maximum of 80 mg). Reluctance to intensify therapy to attain accepted targets in high-risk individuals suggests a degree of clinical inertia not explained by objective evidence of dose-dependent intolerance.

Elevated blood pressure and the cardiometabolic syndrome are often difficult clinical challenges specifically related to fusing appropriate lifestyle modifications and antihypertensive agents. This case illustrates some of the factors clinicians have utilized in approaching patients with this common but challenging clinical situation.

This subgroup analysis of the Irbesartan/Hydrochlorothiazide (HCTZ) Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/HCTZ fixed combinations in adults with uncontrolled systolic blood pressure (SBP) (140-159 mm Hg; 130-159 mm Hg for type 2 diabetes mellitus [T2DM]) after >or=4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). In the intent-to-treat analysis, mean change from baseline (end of placebo phase) off all previous therapy to Week 18 (study end) in T2DM patients (n=227) was -18.2+/-14.1 mm Hg for SBP (primary end point; p<0.001) and -8.7+/-8.2 mm Hg for diastolic blood pressure (p<0.001). Mean SBP/diastolic blood pressure changes in patients with the metabolic syndrome (n=345) were -21.0+/-14.3/-10.4+/-8.5 mm Hg (p<0.001). Overall, 56% (95% confidence interval, 49%-62%) of T2DM and 73% (95% confidence interval, 68%-77%) of metabolic syndrome patients achieved SBP goal (<140 mm Hg; <130 mm Hg for T2DM). Goal attainment rates were significantly higher among women with the metabolic syndrome than men. Treatments appeared to be well tolerated. Irbesartan/HCTZ fixed combinations achieved SBP goals in over half of the T2DM patients and nearly three quarters of patients with the metabolic syndrome, with SBP uncontrolled on antihypertensive monotherapy.

Heart disease and stroke are the most life-threatening consequences of diabetes mellitus, with mortality rates up to two to four times higher for persons with diabetes vs. those without and accounting for up to 65% of deaths. The cardiometabolic syndrome is a potent indicator of future risk of type 2 diabetes and concomitant increased potential for cardiovascular morbidity and mortality. Pharmacologic treatment is usually necessary to improve blood pressure and lipids, thereby decreasing the risk of cardiovascular disease. The reduction of cardiovascular and renal risk with type 2 diabetes and elevated blood pressure are compelling indications for thiazide diuretics, blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and calcium channel blockers. Nevertheless, most patients with type 2 diabetes and elevated blood pressure will require two or more agents to lower blood pressure to the recommended goal of <130/80 mm Hg, and combination therapy may be beneficial. In patients with the cardiometabolic syndrome without type 2 diabetes, the present goal is to maintain BP <140/90 mm Hg, although recent data suggest potential decrease in the progression of prehypertension to hypertension with antihypertensive medication. Furthermore, blockers of the renin-angiotensin system may actually prevent newonset diabetes. It is reasonable for patients with type 2 diabetes and cardiovascular disease to achieve an optional low-density lipoprotein cholesterol (LDL-C) goal <70 mg/dL, and statin therapy should be considered regardless of baseline LDL-C level. In patients with the cardiometabolic syndrome without type 2 diabetes and calculated moderately high-risk status (two or more risk factors; 10-year risk, 10%-20%), the present goal for LDL-C is <130 mg/dL, with perhaps a therapeutic option of <100 mg/dL, and in patients with the cardiometabolic syndrome at lower risk, the LDL-C goal remains <160 mg/dL. Multifactorial management must be utilized to prevent progression of cardiovascular risk with the cardiometabolic syndrome and the ravages of cardiovascular disease in persons with type 2 diabetes, including antiplatelet therapy with aspirin.

The potential benefit of drug therapy for prehypertension and the cardiometabolic syndrome has previously not been confirmed. This case represents a patient who may show slowing or avoiding progression from prehypertension to hypertension based on recent trial evidence and assists the clinician in identifying the risk associated with blood pressure elevation before a conventional cut point of 140/90 mm Hg.

The National Cholesterol Education Program defines the metabolic syndrome as three or more of five abnormalities: waist circumference of >40 in (102 cm) for men or >35 in (88 cm) for women, triglyceride level of > or =150 mg/dL, high-density lipoprotein cholesterol of <40 mg/dL in men or <50 mg/dL in women, blood pressure of > or =130 or > or =85 mm Hg, and fasting glucose of > or =110 mg/dL. It is related to insulin resistance, but the two terms are not synonymous. Both are associated strongly with obesity. The metabolic syndrome is important as an indicator of increased risk of cardiovascular disease (CVD) in patients with and without clinical CVD. The CVD risk of the metabolic syndrome is greater than that conferred by any single CVD risk factor. Since risk factors tend to cluster, if one component of the metabolic syndrome is present, one should assess for other risk factors. The metabolic syndrome is also predictive of new-onset type 2 diabetes. Early diagnosis provides justification for measures that can improve components of the syndrome and reduce CVD risk. The management strategy for metabolic syndrome focuses on overall CVD risk rather than single risk factors; effective therapy includes priority for weight reduction and increased physical activity. Pharmacotherapy is typically needed for control of high blood pressure, hypercoagulability, and increased levels of blood glucose and triglycerides.

The metabolic syndrome and type 2 diabetes mellitus are increasingly associated with cardiovascular disease morbidity and mortality in African Americans. African Americans are specifically prone to the negative effects of hypertension and risk factor clustering associated with the metabolic syndrome and diabetes. Data demonstrate a decrease in cardiovascular events in diabetic patients with secondary prevention and, most recently, primary prevention with lipid-lowering therapy. African Americans should benefit from intense risk factor control, including antihypertensive therapy and lipid lowering, to prevent cardiovascular disease. Appropriate lifestyle modification programs, glucose control, and cardiovascular risk reduction therapy will reduce the excessive morbidity and mortality in this population.

The Metabolic Syndrome represents a specific clustering of cardiovascular risk factors. One of several recently proposed definitions encompasses 3 or more of the following 5 abnormalities: waist circumference > 102 cm in men or > 88 cm in women, serum triglyceride level > or = 150 mg/dL, high-density lipoprotein cholesterol level < 40 mg/dL in men or < 50 mg/dL in women, blood pressure (BP) > or = 130/> or = 85 mm Hg and serum glucose > or = 110 mg/dL. The diagnosis of Metabolic Syndrome allows early recognition of an increased risk of cardiovascular disease. African Americans have the highest coronary heart disease mortality of any ethnic group in the United States. African-American women and Hispanic men and women have the highest prevalence of the Metabolic Syndrome. This phenomenon is attributable mainly to the disproportionate occurrence of elevated BP, obesity, and diabetes in African Americans, and the high prevalence of obesity and diabetes in Hispanics. Management of the Metabolic Syndrome consists primarily of modification or reversal of the root causes and direct therapy of the risk factors. The first strategy involves weight reduction and increased physical activity, both of which can improve all components of the syndrome. The second strategy often involves drug treatment of the individual risk factors to further improve BP, lipids, and glucose thereby decreasing the risk of cardiovascular disease. This comprehensive review is provided as part of the educational activities of the African-American Lipid and Cardiovascular Council (AALCC).