K-Mg-citrate as a BP lowering agent in African Americans; role of natriuresis

Summary

Principal Investigator: ROBERT FRANKLIN REILLY
Abstract: DESCRIPTION (provided by applicant): Essential hypertension is common, affecting 50 million adults in the United States and is a leading cause of cardiovascular death. Multiple studies show that the prevalence of hypertension is increased in African Americans. Racial differences are even more pronounced for severe forms of hypertension, and severe consequences of hypertension such as stroke and kidney disease, making strategies for its control and treatment in this population critical. A variety of modifiable and nonmodifiable factors are likely responsible for this, including differences in dietary intake. Non-pharmacologic approaches, comprised of lifestyle modifications such as exercise, reduction in alcohol consumption, weight loss, and dietary manipulation are accepted as first line management of stage I hypertension. Given that African Americans have a higher prevalence of obesity and lower dietary potassium intake compared to Caucasians (these factors affect blood pressure), a stronger emphasis on lifestyle modification is justified. The DASH diet, which is rich in fruits, vegetables, whole grains, and low fat dairy products significantly lowers blood pressure in African Americans (systolic blood pressure 6.9 mmHg and diastolic blood pressure 3.7 mmHg). Blood pressure lowering is mediated via the combined effects of the diet's three key components: potassium;magnesium;and alkali. When combined with sodium restriction in mildly hypertensive African Americans the diet lowered blood pressure to the same degree as single drug treatment (11 mmHg systolic and 6 mmHg diastolic). Although dietary measures lower blood pressure in the short term, lifestyle modification is hard to maintain in the long term, especially with a diet as complex as DASH. If the key components of the diet could be provided in a pill form, that was associated with minimal side effects, this would be a major advance in hypertension treatment. A new formulation of potassium magnesium citrate (K4MgCit2) is such a pill. Its components are well absorbed via the gastrointestinal tract and it has minimal side effects. In this proposal we will test the hypothesis that lifestyle modification in pill form can reduce blood pressure and specifically that two major components of the DASH diet, magnesium and citrate, confer blood pressure lowering in part by improving natriuresis in response to acute and chronic sodium loading. In aim 1 we will conduct a crossover clinical trial examining the effects of supplemental magnesium and citrate, under constant potassium intake, in African Americans with pre-hypertension and mild hypertension on both high and low sodium intake. It is expected that blood pressure will be lower on K4MgCit2 versus KCl at both sodium intakes. In aim 2 we will examine whether the blood pressure effect correlates with sodium excretion by the kidney. The goal of the second aim is to test whether K4MgCit2 improves renal sodium excretion and whether this correlates with blood pressure reduction. PUBLIC HEALTH RELEVANCE: Hypertension is a major cause of morbidity and mortality in the United States, especially in the African American population where the prevalence, consequences, and severity of hypertension are at their highest;making strategies for its control and treatment in this population critical. Although a variety of modifiable and nonmodifiable factors are likely responsible for this, non-pharmacological lifestyle modifications such as changes in diet were shown to have significant blood pressure lowering effects in African Americans. Lifestyle modifications are, however, difficult to sustain in the long-term but if the key components of dietary modification could be provided in a pill form, that was associated with minimal side effects, this would be a major advance in hypertension treatment.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Klotho: a novel regulator of calcium and phosphorus homeostasis
    Chou Long Huang
    Department of Internal Medicine, Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390 8856, USA
    Pflugers Arch 462:185-93. 2011

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Publications1

  1. ncbi Klotho: a novel regulator of calcium and phosphorus homeostasis
    Chou Long Huang
    Department of Internal Medicine, Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390 8856, USA
    Pflugers Arch 462:185-93. 2011
    ..Through its systematic as well as renal actions, Klotho is emerging as a principal calciophosphoregulatory hormone...