Serum Magnesium and Risk of SCD in the ARIC Study
Background We hypothesized that serum magnesium (Mg) is associated with increased risk of sudden cardiac death (SCD).
Methods The Atherosclerosis Risk in Communities Study assessed risk factors and levels of serum Mg in a cohort of 45- to 64-year-old subjects in 1987–1989 (n = 14,232). After an average of 12 years of follow-up, we observed 264 cases of SCD, as determined by physician review of all suspected cases. We used proportional hazards regression to evaluate the association of serum Mg with risk of SCD.
Results Individuals in the highest quartile of serum Mg were at significantly lower risk of SCD in all models. This association persisted after adjustment for potential confounding variables, with an almost 40% reduced risk of SCD (hazard ratio 0.62, 95% CI 0.42–0.93) in quartile 4 versus 1 of serum Mg observed in the fully adjusted model.
Conclusions This study suggests that low levels of serum Mg may be an important predictor of SCD. Further research into the effectiveness of Mg supplementation for those considered to be at high risk for SCD is warranted.
Sudden cardiac death (SCD) is a major public health problem comprising more than half of all cardiovascular disease (CVD) deaths in the United States. Even with estimates of coronary heart disease (CHD) mortality declining by >50% from 1950 to 1999, the relative proportion of SCD of all CVD deaths in the United States simultaneously increased during this time. Secular trends in Olmsted County, Minnesota, from 1979 to 2003 have shown much larger declines in in-hospital death rates, with declines in out-of-hospital death rates occurring much more slowly. Major risk factors for SCD include hypertension, diabetes, smoking, family history of myocardial infarction (MI), and obesity; but the majority of SCDs occur in those with no prior history of CVD.
Magnesium (Mg), a micronutrient and common cation in the human body, is a natural calcium (Ca) antagonist and modulates vasomotor tone, blood pressure, and peripheral blood flow. Although virtually all Mg is stored in cells, low levels of serum Mg are usually predictive of low levels of total body Mg as well. Previous epidemiologic studies have reported that serum and dietary Mg is associated inversely with CVD risk factors such as hypertension, type 2 diabetes mellitus, and the metabolic syndrome, in addition to CHD. Additional evidence from ecologic, clinical, and autopsy studies has shown higher Mg to be potentially protective against SCD; but no prospective studies have reported the association of Mg levels with incidence of SCD in the general population. In addition to its role in the regulation of blood pressure and maintenance of vascular smooth muscle tone, Mg deficiencies are known to cause ventricular arrhythmias, the most common precursors to SCD. Serum Mg levels are modified by intake of dietary Mg, Ca, and potassium (K), in addition to alcohol intake and physical exercise.
Previous studies in the Atherosclerosis Risk in Communities (ARIC) cohort have shown that serum Mg levels are associated inversely with incidence of hypertension, CHD, and diabetes. In 3 of these studies, there were no associations between dietary Mg as measured from a food frequency questionnaire and these outcomes. The current study was conducted to assess the relative contribution of serum Mg and dietary Mg intake to the incidence of SCD.
Abstract and Introduction
Abstract
Background We hypothesized that serum magnesium (Mg) is associated with increased risk of sudden cardiac death (SCD).
Methods The Atherosclerosis Risk in Communities Study assessed risk factors and levels of serum Mg in a cohort of 45- to 64-year-old subjects in 1987–1989 (n = 14,232). After an average of 12 years of follow-up, we observed 264 cases of SCD, as determined by physician review of all suspected cases. We used proportional hazards regression to evaluate the association of serum Mg with risk of SCD.
Results Individuals in the highest quartile of serum Mg were at significantly lower risk of SCD in all models. This association persisted after adjustment for potential confounding variables, with an almost 40% reduced risk of SCD (hazard ratio 0.62, 95% CI 0.42–0.93) in quartile 4 versus 1 of serum Mg observed in the fully adjusted model.
Conclusions This study suggests that low levels of serum Mg may be an important predictor of SCD. Further research into the effectiveness of Mg supplementation for those considered to be at high risk for SCD is warranted.
Introduction
Sudden cardiac death (SCD) is a major public health problem comprising more than half of all cardiovascular disease (CVD) deaths in the United States. Even with estimates of coronary heart disease (CHD) mortality declining by >50% from 1950 to 1999, the relative proportion of SCD of all CVD deaths in the United States simultaneously increased during this time. Secular trends in Olmsted County, Minnesota, from 1979 to 2003 have shown much larger declines in in-hospital death rates, with declines in out-of-hospital death rates occurring much more slowly. Major risk factors for SCD include hypertension, diabetes, smoking, family history of myocardial infarction (MI), and obesity; but the majority of SCDs occur in those with no prior history of CVD.
Magnesium (Mg), a micronutrient and common cation in the human body, is a natural calcium (Ca) antagonist and modulates vasomotor tone, blood pressure, and peripheral blood flow. Although virtually all Mg is stored in cells, low levels of serum Mg are usually predictive of low levels of total body Mg as well. Previous epidemiologic studies have reported that serum and dietary Mg is associated inversely with CVD risk factors such as hypertension, type 2 diabetes mellitus, and the metabolic syndrome, in addition to CHD. Additional evidence from ecologic, clinical, and autopsy studies has shown higher Mg to be potentially protective against SCD; but no prospective studies have reported the association of Mg levels with incidence of SCD in the general population. In addition to its role in the regulation of blood pressure and maintenance of vascular smooth muscle tone, Mg deficiencies are known to cause ventricular arrhythmias, the most common precursors to SCD. Serum Mg levels are modified by intake of dietary Mg, Ca, and potassium (K), in addition to alcohol intake and physical exercise.
Previous studies in the Atherosclerosis Risk in Communities (ARIC) cohort have shown that serum Mg levels are associated inversely with incidence of hypertension, CHD, and diabetes. In 3 of these studies, there were no associations between dietary Mg as measured from a food frequency questionnaire and these outcomes. The current study was conducted to assess the relative contribution of serum Mg and dietary Mg intake to the incidence of SCD.