Serum Magnesium and the Risk of Death From Coronary Heart Disease and Sudden Cardiac Death

Abstract

Background: Low serum magnesium has been implicated in cardiovascular mortality, but results are conflicting and the pathway is unclear. We studied the association of serum magnesium with coronary heart disease (CHD) mortality and sudden cardiac death (SCD) within the prospective population-based Rotterdam Study, with adjudicated end points and long-term follow-up.

Methods and results: Nine-thousand eight-hundred and twenty participants (mean age 65.1 years, 56.8% female) were included with a median follow-up of 8.7 years. We used multivariable Cox proportional hazard models and found that a 0.1 mmol/L increase in serum magnesium level was associated with a lower risk for CHD mortality (hazard ratio: 0.82, 95% CI 0.70-0.96). Furthermore, we divided serum magnesium in quartiles, with the second and third quartile combined as reference group (0.81-0.88 mmol/L). Low serum magnesium (≤0.80 mmol/L) was associated with an increased risk of CHD mortality (N=431, hazard ratio: 1.36, 95% CI 1.09-1.69) and SCD (N=217, hazard ratio: 1.54, 95% CI 1.12-2.11). Low serum magnesium was associated with accelerated subclinical atherosclerosis (expressed as increased carotid intima-media thickness: +0.013 mm, 95% CI 0.005-0.020) and increased QT-interval, mainly through an effect on heart rate (RR-interval: -7.1 ms, 95% CI -13.5 to -0.8). Additional adjustments for carotid intima-media thickness and heart rate did not change the associations with CHD mortality and SCD.

Conclusions: Low serum magnesium is associated with an increased risk of CHD mortality and SCD. Although low magnesium was associated with both carotid intima-media thickness and heart rate, this did not explain the relationship between serum magnesium and CHD mortality or SCD. Future studies should focus on why magnesium associates with CHD mortality and SCD and whether intervention reduces these risks.

Keywords: cardiovascular diseases; death, sudden; epidemiology; mortality; risk factors.

Figure 1

Overlap between the classification of coronary heart disease mortality (as a cause of death) and sudden cardiac death (as a mode of death). Among all 2303 participants who died during follow‐up, 780 died due to cardiovascular disease, of which 431 participants were classified as coronary heart disease mortality. Of these 431 participants, 187 were also classified as sudden cardiac death. Seventeen participants were classified as sudden cardiac death and cardiovascular deaths (but not coronary heart disease) and 13 participants were classified as sudden cardiac death but could otherwise not be classified as cardiovascular deaths.

Figure 2

Estimated cumulative probability curves for coronary heart disease mortality, nonsudden coronary heart disease mortality, and sudden cardiac death. Estimated cumulative probability curves are shown for coronary heart disease mortality (A), nonsudden coronary heart disease mortality (B), and sudden cardiac death (C) between different groups of serum magnesium levels, taking into account the competing risk of death by other causes. Low serum magnesium is defined as 0.34 to 0.80 mmol/L, medium serum magnesium (reference) as 0.81 to 0.88 mmol/L, and high serum magnesium as 0.89 to 1.74 mmol/L.