The role of nutrition, nutraceuticals, vitamins, antioxidants, and minerals in the prevention and treatment of hypertension.

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 or environmental causes and prescription drug use. 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 on overall health costs. The diagnosis and treatment of these nutrient deficiencies can reduce blood pressure; improve vascular health, endothelial dysfunction, and vascular biology; and decrease cardiovascular events. Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and target organ damage (TOD). Endothelial activation, oxidative stress, inflammation, autoimmune vascular dysfunction, and vascular smooth-muscle dysfunction are initial events in hypertension. Nutrient gene interactions determine a broad array of phenotypic consequences, such as vascular problems and hypertension. In addition to other lifestyle modifications, optimal nutrition, nutraceutical supplements, vitamins, antioxidants, minerals, weight loss, exercise, smoking cessation, and moderate restriction of alcohol and caffeine can prevent and control hypertension in many patients. An integrative approach combining these lifestyle suggestions with the correct pharmacologic treatment will best achieve new goals for blood pressure levels, reduce cardiovascular risk factors, improve vascular biology and vascular health, reduce cardiovascular TOD, and reduce health care expenditures. In this article, the expanded scientific role for nutraceutical supplements in the treatment of essential hypertension will be discussed. It is the purpose of this article to review only the hypertension clinical trials that have evaluated the clinical use and efficacy of nutrition, weight loss, exercise, and nutritional supplements, vitamins, minerals, and antioxidants.

The importance of potassium in managing hypertension.

Dietary potassium intake has been demonstrated to significantly lower blood pressure (BP) in a dose-responsive manner in both hypertensive and nonhypertensive patients in observational studies, clinical trials, and several meta-analyses. In hypertensive patients, the linear dose-response relationship is a 1.0 mm Hg reduction in systolic BP and a 0.52 mm Hg reduction in diastolic BP per 0.6 g per day increase in dietary potassium intake that is independent of baseline potassium deficiency. The average reduction in BP with 4.7 g (120 mmol) of dietary potassium per day is 8.0/4.1 mm Hg, depending race and on the relative intakes of other minerals such as sodium, magnesium, and calcium. If the dietary sodium chloride intake is high, there is a greater BP reduction with an increased intake of dietary potassium. Blacks have a greater decrease in BP than Caucasians with an equal potassium intake. Potassium-induced reduction in BP significantly lowers the incidence of stroke (cerebrovascular accident, CVA), coronary heart disease, myocardial infarction, and other cardiovascular events. However, potassium also reduces the risk of CVA independent of BP reductions. Increasing consumption of potassium to 4.7 g per day predicts lower event rates for future cardiovascular disease, with estimated decreases of 8% to 15% in CVA and 6% to 11% in myocardial infarction.

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 mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction.

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.

Efficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia: results of the AVALON trial.

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.

Is population-wide diuretic use directly associated with the incidence of end-stage renal disease in the United States? A hypothesis.

BACKGROUND: We introduce the hypothesis that population-wide use of diuretics might be associated with acceleration of the incidence of end-stage renal disease (ESRD). METHODS: Based on the technique of data fusion, pooled-data trends in disease incidence and antihypertensive medication use were examined to determine whether changes in drug use patterns are predictive of disease emergence in the United States. National databases for all-cause cardiovascular disease (CVD) mortality and stroke mortality from the National Vital Statistics Registry, renal failure data obtained from the United States Renal Data Service, and drug information obtained from IMS Health (Fairfield, CT) were examined. RESULTS: A statistically significant inverse relationship was observed between all-cause CVD mortality rates and ESRD incidence rates for the period 1980 to 1998 (r = -0.98948; P < .0001). A statistically significant direct time-lagged relationship was found between both annual changes in diuretic distribution and total diuretic expenditure to annual changes in the ESRD growth rate (r = 0.754, P = .03, r(2) = 0.568, 95% CI for slope = 0.08975 to 1.3010). CONCLUSIONS: Increasing annual diuretic distribution in the US is directly associated with accelerated time-lagged growth rates of ESRD incidence. One potential explanation is that diuretic therapy could promote ESRD expression. A large-scale, randomized, controlled trial to investigate acceleration of ESRD by diuretics would be justifiable. The data invites the hypothesis that reliance on nondiuretic antihypertensive therapies such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers might attenuate the epidemic rise of ESRD that is prevalent in the United States.

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.

Addressing the global cardiovascular risk of hypertension, dyslipidemia, and insulin resistance in the southeastern United States.

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.

Role of mercury toxicity in hypertension, cardiovascular disease, and stroke.

Mercury has a high affinity for sulfhydryl groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (N-acetyl-L-cysteine, alpha-lipoic acid, L-glutathione), with subsequent decreased oxidant defense and increased oxidative stress. Mercury binds to metallothionein and substitute for zinc, copper, and other trace metals, reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in adenosine triphosphate, depletion of glutathione, and increased lipid peroxidation. Increased oxidative stress and reduced oxidative defense are common. Selenium and fish containing omega-3 fatty acids antagonize mercury toxicity. The overall vascular effects of mercury include increased oxidative stress and inflammation, reduced oxidative defense, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, and immune and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, coronary heart disease, myocardial infarction, cardiac arrhythmias, reduced heart rate variability, increased carotid intima-media thickness and carotid artery obstruction, cerebrovascular accident, generalized atherosclerosis, and renal dysfunction, insufficiency, and proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury inactivates catecholaminei-0-methyl transferase, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to mercury-induced heavy metal toxicity. Mercury toxicity should be evaluated in any patient with hypertension, coronary heart disease, cerebral vascular disease, cerebrovascular accident, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, and serum should be performed.

Nutrition and nutraceutical supplements in the treatment of hypertension.

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 and environmental causes, and prescription drug use. Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and target organ damage sequelae. Endothelial activation, oxidative stress and vascular smooth muscle dysfunction (hypertrophy, hyperplasia and remodeling) are initial events that initiate 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, delay the onset, reduce the severity, treat 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 health, reduce target organ damage, including coronary heart disease, stroke, congestive heart failure and renal disease, and reduce healthcare expenditure. The expanded scientific roles for nutraceutical supplements will be discussed in relation to the prevention and treatment of essential hypertension and cardiovascular diseases.

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$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.

Treatment of hypertension with nutraceuticals, vitamins, antioxidants and minerals.

Hypertension is the most common reason for visits to physicians' offices and the primary reason for prescription drug use. The target organ damage associated with hypertension, such as stroke, myocardial infarction, congestive heart failure, renal disease and large artery disease, can be mitigated by aggressive nondrug and drug therapies. Hypertension is a syndrome of various metabolic, functional and structural abnormalities that must be viewed in a more global setting of cardiovascular risk. Aggressive detection, evaluation and treatment of the 'blood vessel health' is mandatory to modern hypertensive care. Lifestyle modifications in conjunction with vitamins, minerals, antioxidants, nutraceutical supplements, optimal nutrition and drug therapy will prevent and treat hypertension and its sequelae while addressing global cardiovascular risk, vascular biology, endothelial dysfunction and overall vascular health.

Nutraceuticals, vitamins, antioxidants, and minerals in the prevention and treatment of hypertension.

Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and target organ damage sequelae. Endothelial activation, oxidative stress, and vascular smooth muscle dysfunction (hypertrophy, hyperplasia, remodeling) 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, delay the onset, reduce the severity, treat, and control hypertension in many patients. An integrative approach combining these lifestyle suggestions with the correct pharmacological treatment will best achieve new goal blood pressure levels, reduce cardiovascular risk factors, improve vascular biology and vascular health, and reduce target organ damage including coronary heart disease, stroke, congestive heart failure, and renal disease. The expanded scientific roles for nutraceutical supplements will be discussed in relation to the prevention and treatment of essential hypertension with emphasis on mechanisms of action and clinical integration with drug therapy as indicated based, in part, on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, the European Society of Hypertension, the European Society of Cardiology, the International Society of Hypertension, the Canadian Society of Hypertension, and other hypertension guidelines.