The cohort at risk for SCD included 7,887 women and 6,345 men aged 45–64 years at baseline. Serum Mg levels measured at visits 1 and 2 ranged from 0.4 to 3.1 mEq/L and appeared to be normally distributed, with 98% of individuals from 1.2 to 2.0 mEq/L. As shows, LDL-c and HDL-c, heart rate-adjusted QT interval, serum K, physical activity, education, and dietary Mg intake were all associated positively with levels of serum Mg. Fasting triglycerides, pack-years of smoking, systolic blood pressure, hypertension, diabetes, use of diuretics, female sex, being African-American, and education were associated inversely with serum Mg. There were no differences in the percentage of current or former smokers, mean weekly alcohol intake, or daily total energy intake by quartile of serum Mg.
Age-, race-, sex-, and field center-adjusted means or percentages of potential Sudden Cardiac Death risk factors by serum Magnesium quartiles
Through May 31, 2001, 264 individuals were classified as having died from either definite (n=217) or possible (n=47) SCD. There were 46 events in Forsyth County, 93 in Jackson, 48 in Minneapolis, and 77 in Washington County. shows that the age-, race-, sex-, and field center-adjusted risk of SCD was inversely associated with serum Mg (p for linear trend <0.0001). Compared to the lowest quartile of Mg, the risk of SCD was 55% lower (HR=0.45, 95% C.I., 0.31–0.67) in the highest Mg quartile and 47% lower in the second highest quartile (HR=0.53, 95% C.I., 0.38–0.74). This strong association persisted after adjustment for potentially confounding variables, including baseline measures of fasting lipids, heart rate adjusted-QT interval, serum K, physical activity score, smoking status and pack years, regular alcohol intake, and education level (Model 2) (p for linear trend = 0.0006), but point estimates of the association were attenuated modestly (HR = 0.55 for quartile 4 vs. 1, 95% C.I. = 0.37–0.83; and HR = 0.62 for quartile 3 vs. 1, 95% C.I. = 0.44–0.88). Apart from lower Mg, only greater age, male sex, being African-American, not being at the Forsyth County field center, lower HDL, higher LDL, greater pack-years of smoking, and less education were associated with greater risk of SCD in Model 2.
Crude incidence rate and adjusted hazard ratios (95% CI) of definite or possible Sudden Cardiac Death by baseline serum Magnesium quartiles in the ARIC Study (1987 to 2001)
After further adjustment for prevalent diabetes, prevalent hypertension, and use of diuretics (Model 3), each associated with greater risk of SCD, the serum Mg association was attenuated slightly (p for linear trend = 0.006), with both quartiles 4 (HR = 0.62, 95% C.I. = 0.42–0.93) and 3 (HR = 0.70, 95% C.I. = 0.49–0.99) at significantly reduced risk of SCD when compared to the lowest quartile of serum Mg. Restriction of this analysis to only definite cases of SCD (n=217) attenuated these results, with quartile 4 (HR = 0.72, 95% C.I. = 0.46–1.11) no longer associated with a reduced risk of SCD (data not shown).
In order to assess the specificity of this association, we restricted the definition of SCD in three ways: cases that were 1) unwitnessed, 2) determined to have taken place outside of the hospital, or 3) determined to not be associated with MI by the physician reviewers ( bottom). The risk of unwitnessed SCD in the fully-adjusted model was marginally lower than for all SCD cases for quartile 4 compared to quartile 1 (HR = 0.49, 95% C.I. = 0.25–0.99), but the linear trend was no longer significant (p = 0.07). Restricting the SCD cases to out-of-hospital events did not change the overall association. The serum Mg association with SCD was somewhat stronger for cases not associated with MI, with quartile 4 (HR = 0.51, 95% C.I. = 0.32–0.83) at one-half the risk of death as the lowest quartile, greatly excluding the null.
To explore potential effect modification by prevalent CHD, we redid the analysis several different ways. Additional analyses which excluded prevalent CHD cases at baseline and censored individuals at the time of an incident non-fatal event (definite or possible MI, ECG-detected silent MI between examinations, coronary revascularization), reducing the number of cases by about half, showed similar, albeit weaker, results with wide confidence intervals including the null. Alternatively, adjusting for incident CHD occurrence before SCD by modeling it as a time-dependent covariate attenuated the association, with quartile 4 (HR = 0.69, 95% C.I. = 0.46–1.04), no longer significantly associated with a reduced risk of SCD. There was no evidence of effect modification by prevalent or incident CHD on the association of serum Mg with SCD. None of the two-way interactions of sex, race, heart rate-adjusted QT interval, serum K, and diuretic use with serum Mg was statistically significant at p<0.05.
illustrates the pattern of risk in those individuals who had serum Mg measured at both clinic examinations (n=13,010 at risk, 194 cases). For this figure, the cohort was dichotomized at the median value of both measurements of serum Mg, thereby comparing the upper two quartiles vs. lower two. Compared to those with Mg < median at both visits, individuals with serum Mg above the median at only one visit were not at a different risk of SCD. However, the risk of SCD was 42% lower in those individuals with serum Mg above the median at both visits (HR = 0.58, 95% C.I. = 0.37–0.89).
Adjusted* hazard ratios (95% CI) of definite or possible Sudden Cardiac Death by categories of serum Magnesium at two ARIC visits
We also compared this association to that of serum Mg with CHD deaths not classified as definite or possible SCD. Over the same time period, 868 individuals were classified as having died from CHD, but not SCD. In all three models, the association was present, but attenuated compared with the association of Mg level with SCD (Model 3 HR = 0.69, 95% C.I. = 0.56–0.84). Similar analyses were performed with dietary Mg as the exposure of interest. There was no evidence of an association between dietary Mg intake and risk of SCD in any of the models described above (data not shown).