Mark C. Houston

Role of Mercury Toxicity in Hypertension, Cardiovascular Disease, and Stroke

J Clin Hypertens (Greenwich). 2011;13:621–627. ©2011 Wiley Periodicals, Inc.

Potassium, magnesium, and calcium: their role in both the cause and treatment of hypertension.

Despite advances in the prevention and treatment of hypertension over the past decade, hypertension remains an important public health challenge. Recent efforts to reduce the prevalence of hypertension have focused on nonpharmacologic means, specifically diet. An increased intake of minerals such as potassium, magnesium, and calcium by dietary means has been shown in some but not all studies to reduce blood pressure in patients with hypertension. This review will discuss the roles of potassium, magnesium, and calcium in the prevention and treatment of essential hypertension with specific emphasis on clinical trial evidence, mechanism of action, and recommendations for dietary intake of these minerals. A high intake of these minerals through increased consumption of fruits and vegetables may improve blood pressure levels and reduce coronary heart disease and stroke.

The role of magnesium in hypertension and cardiovascular disease.

J Clin Hypertens (Greenwich). 2011;13:843–847. ©2011 Wiley Periodicals, Inc.

Addressing the Global Cardiovascular Risk of Hypertension, Dyslipidemia, Diabetes Mellitus, and the Metabolic Syndrome in the Southeastern United States, Part II: Treatment Recommendations for Management of the Global Cardiovascular Risk of Hypertension, Dyslipidemia, Diabetes Mellitus, and the Metabolic Syndrome

An aggressive global approach to screening and to the management of the metabolic syndrome is recommended to slow the growth of the syndrome throughout the United States. Prevention should begin in childhood with healthy nutrition, daily physical activity, and annual measurement of weight, height, and blood pressure beginning at 3 years of age. Such screenings will identify cardiovascular risk factors early, allow the health care provider to define global cardiovascular risk with the COSEHC Cardiovascular Risk Assessment Tool, and allow treatment of each risk factor. Lifelong lifestyle modifications and pharmacologic therapy will be required in most patients. Antihypertensive therapy for these patients should begin with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker unless a compelling indication for another drug is present. Metformin should be considered the first drug for glucose control in the patient with type 2 diabetes. A statin should be used initially for hyperlipidemia unless contraindicated. Combinations of antihypertensive, antiglycemic, and lipid-lowering agents will often be required.

The role of cellular micronutrient analysis, nutraceuticals, vitamins, antioxidants and minerals in the prevention and treatment of hypertension and cardiovascular disease

Macronutrient and micronutrient deficiencies are very common in the general population and may be even more common in patients with hypertension and cardiovascular disease due to genetic, environmental causes and prescription drug use. The Hypertension Institute in Nashville, TN, has evaluated micronutrient deficiencies and oxidation status, in a group of hypertensive versus normotensive patients. There are significant differences in numerous intracellular micronutrients and oxidation status between these two groups. Replacement of the micronutrient deficiencies, as well as high-dose therapy of selected nutraceuticals in combination with optimal diet, exercise and weight management resulted in control of blood pressure to goal levels in 62% of the hypertensive population (as defined by JNC 7) over a period of 6 months with complete tapering and discontinuation of antihypertensive drugs. These deficiencies will have an enormous impact on present and future cardiovascular health and outcomes such as hypertension, myocardial infarction, stroke and renal disease and overall health costs. It is estimated that the annual savings in drug costs alone for the treatment of hypertension could be as much as US

Addressing the Global Cardiovascular Risk of Hypertension, Dyslipidemia, and Insulin Resistance in the Southeastern United States

10 billion. Diagnosis and treatment of these nutrient deficiencies and improvement in oxidation status using functional intracellular assessments will reduce blood pressure, improve vascular health, endothelial dysfunction, vascular biology and cardiovascular events. Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and target organ damage sequelae. Endothelial activation, oxidative stress, inflammation and vascular smooth muscle dysfunction are initial events that start hypertension. Nutrient-gene interactions determine a broad array of phenotypic consequences such as vascular problems and hypertension. Optimal nutrition, nutraceuticals, vitamins, antioxidants, minerals, weight loss, exercise, smoking cessation and moderate restriction of alcohol and caffeine in addition to other lifestyle modifications can prevent and control hypertension in many patients. An integrative approach combining these lifestyle suggestions with the correct pharmacologic treatment will best achieve new goal blood pressure levels, reduce cardiovascular risk factors, improve vascular biology and vascular health, reduce cardiovascular target organ damage and reduce healthcare expenditure. The expanded scientific roles for nutraceutical supplements are discussed in relation to the prevention and treatment of essential hypertension and cardiovascular diseases with emphasis on mechanisms of action and clinical integration with drug therapy with hypertension guidelines. It is the purpose of this paper to review only the hypertension clinical trials that have evaluated the clinical use and efficacy of nutrition, weight loss, exercise and selected nutritional supplements, vitamins, minerals and antioxidants. Numerous clinical trials have evaluated the use of nutritional supplements such as beta carotene, selenium, vitamin C and vitamin E in the prevention of coronary heart disease and stroke yielding conflicting results (positive, neutral and negative). In many of these clinical trials there are enormous clinical design problems, methodologic flaws, varied patient population, variable dose and type of vitamin use, improper selection of vitamin used and many other issues that make the studies difficult to interpret. It is beyond the scope of this paper to review these trials. The reader is referred to the vast literature on this subject.

Efficacy and Safety of Coadministered Amlodipine and Atorvastatin in Patients With Hypertension and Dyslipidemia: Results of the AVALON Trial

An expanded occurrence of the metabolic syndrome in the U.S. population, especially in the Southeastern United States, has raised awareness of a need to revise our approach to the management of global cardiovascular risk factors while underscoring a need for more aggressive interventions and prevention measures. In defining the components of the metabolic syndrome and the interrelationship among obesity, hypertension, dyslipidemia, and insulin resistance, a basic framework for the medical management of this syndrome has been defined. In Part I of the consensus report prepared by the Workgroup on Medical Guidelines of the Consortium for Southeastern Hypertension Control (COSEHC), we analyze the components of the metabolic syndrome, discuss its pathophysiology, and recommend an approach to the quantitative analysis of the risk factors contributing to excess cardiovascular death in the region.

New insights and approaches to reduce end-organ damage in the treatment of hypertension: Subsets of hypertension approach

The AVALON study was a randomized, multicenter trial to assess the efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia. Phase one was an 8‐week, double‐blind, double‐dummy, placebo‐controlled period whereby patients received amlodipine 5 mg, atorvastatin 10 mg, amlodipine 5 mg and atorvastatin 10 mg, or placebo. Thereafter, all patients received single‐blind amlodipine 5 mg and atorvastatin 10 mg for 8‐weeks, followed by 12 weeks of open‐label treatment where doses could be titrated to improve low‐density lipoprotein cholesterol and blood pressure control. A total of 847 patients entered the double‐blind phase. At Week 8, 45% of the patients receiving amlodipine 5 mg and atorvastatin 10 mg reached both their blood pressure and low‐density lipoprotein cholesterol goals, compared with 8.3% with amlodipine (p<0.001), 28.6% with atorvastatin (p<0.001), and 3.5% with placebo. At 28 weeks, 67.1% of patients coadministered amlodipine and atorvastatin (mean doses, 7.6 mg and 28.4 mg, respectively) achieved both targets. Framingham estimated 10‐year risk of coronary heart disease declined from baseline levels of 15.1% to 6.9% at Week 28. Following coadministered treatment, the adverse events reported were similar to either agent alone. Concomitant administration of amlodipine and atorvastatin is an effective and well tolerated treatment for coexisting hypertension and dyslipidemia.

Coadministered Amlodipine and Atorvastatin Produces Early Improvements in Arterial Wall Compliance in Hypertensive Patients With Dyslipidemia

Antihypertensive therapy should be directed toward reduction of all end-organ damage including congestive heart failure, left ventricular hypertrophy, coronary heart disease, myocardial infarction, cerebrovascular accident, and chronic renal failure. The Subsets of hypertension approach is based on pathophysiology, hemodynamics, risk factor reduction for end-organ damage, concomitant diseases and problems, demographics, adverse effects on quality of life, compliance, and total health care costs. This approach provides a more individualized and logical treatment of the hypertensive syndrome and addresses the metabolic and structural abnormalities that are present.

Statins and C-reactive protein levels

BACKGROUND Combining statins with antihypertensive therapy has been demonstrated to provide an early reduction in cardiovascular events. This nested substudy of the AVALON trial assessed the effects of coadministered amlodipine and atorvastatin vs. either therapy alone or placebo on arterial compliance, to evaluate the vascular benefits of coadministered therapy. METHODS During an initial 8-week, double-blind phase, patients with concomitant hypertension and dyslipidemia were randomized into four treatment groups (placebo, amlodipine 5 mg, atorvastatin 10 mg, or coadministered amlodipine 5 mg and atorvastatin 10 mg). The sustained effect of combined therapy was evaluated during subsequent 8-week, single-blind, and 12-week, open-label periods. In the single-blind phase, all patients were coadministered amlodipine 5 mg and atorvastatin 10 mg, which were then titrated to optimize blood pressure and low-density lipoprotein cholesterol control during the open-label phase. Arterial compliance was assessed every 4 weeks using the HDI/Pulsewave CR-2000. RESULTS Overall, 668 patients (61% male, mean age 55 years) were randomized to treatment. A 19% improvement in small artery compliance (C2) was observed with coadministered amlodipine and atorvastatin from baseline to week 8, which was significantly greater than with either treatment alone or with placebo (P = 0.03 to 0.0001). After 28 weeks, C2 was increased from baseline in all groups, but the overall improvement was greatest in the group receiving coadministered drugs for the entire study period (P < 0.05). CONCLUSIONS Early and sustained improvement in small artery compliance was observed following coadministration of amlodipine and atorvastatin, thus demonstrating a vascular benefit with simultaneous treatment of hypertension and dyslipidemia.