TABLE 1.
Characteristics of 16 prospective studies providing 25 risk estimates in 313,041 individuals for circulating or dietary magnesium and risk of total CVD and IHD1
| First author | Study(country) | Cases/total individuals | Age range | Men | CVD2 | Exposure assessment3 | Disease outcome | Disease ascertainment4 | Follow-up (maximum) | Adjustment5 | Quality score6 |
| n | y | % | % | y | |||||||
| Circulating magnesium | |||||||||||
| Reunanen et al (case-control), 1996 (25) | Finnish men (Finland) | 15–69 | 100 | 22.6 | AAS (serum) | 10 (mean) | ++ | 4 | |||
| 220/507 | CVD death | ICD-8-CM codes 390.97–458.99 | |||||||||
| 160/381 | IHD death | ICD-8-CM codes 410.00–414.99 | |||||||||
| Marniemi et al, 1998 (22) | Finnish elderly (Finland) | 142/344 | ≥65 | 52.9 | 19 | AAS (serum) | CVD death | National death register; select cases confirmed at autopsy | 13 | ++ | 5 |
| Liao et al, 1998 (12) | ARIC (USA) | 223/13,922; 96/13,922 | 45–64 | 1000 | 0 | Colorimetric (serum) | IHD total | Minnesota Code, death certificates with next of kin interviews and physician questionnaires; deaths validated by autopsies | 7 | ++ | 5 |
| Ford, 1999 (18) | NHEFS (USA) | 25–74 | 40 | 0 | AAS (serum) | 19 | ++ | 5 | |||
| 2637/12,340 | IHD total | ICD-9-CM codes 410–414 | |||||||||
| 1005/12,340 | IHD death | Death certificates listing codes above | |||||||||
| Leone et al, 2006 (21) | PPS II (France) | 56/4035 | 30–60 | 100 | 1.4 | AAS (serum) | CVD death | ICD-10-CM codes I00–199 | 21 | ++ | 5 |
| Peacock et al, 2010 (13) | ARIC (USA) | 264/14,232 | 45–64 | 45 | 0 | Colorimetric (serum) | SCD | Fatal IHD cases classified by physician committee as definite or possible sudden arrhythmic death | 12 | ++ | 4 |
| Khan et al, 2010 (20)7 | FHS offspring (USA) | 554/3531 | 44.3 (mean) | 48 | 0 | Colorimetric (serum) | CVD total | Panel review of hospital, medical, and Framingham clinic visit notes by using standardized criteria | 20 | ++ | 5.5 |
| Chiuve et al (case-control), 2011 (16) | NHS (USA) | 99/390 | 44–69 | 0 | 40 | Colorimetric (plasma) | SCD | Medical records or next of kin report of death or cardiac arrest within 1 h of symptom onset, arrhythmic death as defined by Hinkle and Thaler | 16 | +++ | 6 |
| Reffelmann et al, 2011 (24) | SHIP (Germany) | 79/3910 | 20–79 | 49 | 5.8 | Colorimetric (serum) | CVD death | ICD-10-CM codes I10–I79 | 12 | ++ | 5.5 |
| Dietary magnesium | |||||||||||
| Elwood et al, 1996 (17) | Caerphilly cohort (Wales) | 45–59 | 100 | 17 | FFQ | 10 | + | 3 | |||
| 269/2172 | IHD total | ICD-9-CM codes 410–414 | |||||||||
| 96/2172 | IHD death | ICD-9-CM code 410 | |||||||||
| Liao et al, 1998 (12) | ARIC (USA) | 223/13,744; 96/13,744 | 45–64 | 1000 | 0 | FFQ | IHD total | Minnesota Code, death certificates with next of kin interviews and physician questionnaires; deaths validated by autopsies | 7 | +++ | 5 |
| Abbott et al, 2003 (14) | HHS (USA) | 548/7172 | 45–68 | 100 | 0 | 24-h recall | IHD total | ECG or cardiac enzyme evidence, SCD, heart failure or arrhythmic death in patients with IHD history, and/or autopsy findings | 15 | +++ | 5 |
| Al-Delaimy et al, 2004 (15) | HPFS (USA) | 1449/39,633 | 40–75 | 100 | 0 | FFQ | IHD total | Next of kin/coworker reports or National Death Index; confirmation with medical/autopsy reports or death certificates; SCD | 12 | +++ | 5 |
| Song et al, 2005 (7) | WHS (USA) | 39–89 | 0 | 0 | FFQ | 11 | ++ | 5.5 | |||
| 1027/35,601 | CVD total | Myocardial infarction symptoms with ECG changes or cardiac enzyme elevation; hospital record of angioplasty or coronary bypass graft; stroke determined by endpoints committee | |||||||||
| 672/35,601 | IHD total | Same as CVD incidence, excluding stroke and final CVD | |||||||||
| Kaluza et al, 2010 (19) | CSM (Sweden) | 819/23,366 | 45–79 | 100 | 0 | FFQ | CVD death | ICD-10-CM codes I00–I79 | 10 | +++ | 5 |
| Chiuve et al, 2011 (16) | NHS (USA) | 505/88,375 | 34–59 | 0 | 0 | FFQ | SCD | Medical records or next of kin report of death or cardiac arrest within 1 h of symptom onset, arrhythmic death as defined by Hinkle and Thaler | 26 | +++ | 6 |
| Otto et al, 2012 (23) | MESA (USA) | 263/5285 | 45–84 | 47 | 0 | FFQ | CVD total | Self-reported diagnoses, death certificates, autopsy reports, medical records reviewed by endpoints committee | 7 | +++ | 5 |
| Zhang et al, 2012 (26) | JACC (Japan) | 1347/35,532 | 40–79 | 0 | 0 | FFQ | CVD death | ICD-10-CM codes I01–I99 | 17 | +++ | 5.5 |
| 1343/23,083 | 100 | CVD death | Same as above | ||||||||
| 246/35,532 | 0 | IHD death | ICD-10-CM codes I20–I25 | ||||||||
| 311/23,083 | 100 | IHD death | Same as above |
AAS, atomic absorption spectrophotometry; ARIC, Atherosclerosis Risk in Communities; CM, clinical modification; CSM, Cohort of Swedish Men; CVD, cardiovascular disease; ECG, electrocardiogram; FFQ, food-frequency questionnaire; FHS offspring, Framingham Heart Study, offspring cohort; HHS, Honolulu Heart Study; HPFS, Health Professionals Follow-Up Study; ICD-CM, International Statistical Classification of Disease Clinical Modification; IHD, ischemic heart disease; JACC, Japan Collaborative Cohort Study; MESA, Multi-Ethnic Study of Atherosclerosis; NHEFS, NHANES I Epidemiologic Follow-Up Study; NHS, Nurses’ Health Study; PPS II, Paris Prospective Study II; SCD, sudden cardiac death; WHS, Women's Health Study.
Prevalent CVD at baseline.
Dietary exposure was assessed by using FFQs or 24-h dietary recalls; circulating magnesium (serum or plasma) was assessed by using colorimetric assays (colorimetric) or AAS.
The CM number indicates the revision number.
The degree of covariate adjustment is indicated by + (sociodemographic variables), ++ (sociodemographic variables and other risk factors), and +++ (sociodemographic variables, other risk factors, and dietary variables). Circulating magnesium was inversely associated with non-white race, prevalence of hypertension, diabetes, use of diuretics, and other cardiovascular drugs, with weak positive correlations with dietary magnesium intake (r ≤ 0.09) (15, 16) and serum potassium and calcium (r ≤ 0.18) (20) and inconsistent associations with BMI, smoking, lipid profiles, and glomerular filtration rate in univariate analyses (13, 16, 20, 21, 24). Two circulating magnesium studies provided estimates, including diabetes and hypertension as time-varying covariates (13, 16); models excluding these variables were used. Most dietary magnesium studies adjusted for intakes of other nutrients (12, 14–16, 19, 23, 26), including potassium (12, 14–16, 26). Few studies have reported the correlation between dietary magnesium and potassium, although r ≥ 0.91 was reported in references 20 and 26. Multivariate-adjusted estimates excluding dietary potassium were used; if the only available multivariable model presented included dietary potassium, it was selected in preference to crude estimates or minimally adjusted models. Dietary magnesium intake was also associated with intakes of energy, calcium, and fiber (r ≤ 0.75), higher educational attainment, and greater physical activity and was inversely associated with BMI, hypertension, and diabetes in univariate analyses (7, 14–16, 19, 26).
Study quality was assessed by using 6 criteria (up to 1 point per criterion), including participation (1 point if key characteristics of source population were described, including record of sampling recruitment method, period and location of recruitment, or reference to previously published study detailing source population characteristics), attrition (1 point if participants/nonparticipants did not differ by key study characteristics), exposure determination (1 point if dietary magnesium was measured by using a validated dietary assessment method; for circulating magnesium, 1 point if measured by using a published AAS or colorimetric method, with absence of evidence of the potential for hemolyzed samples or EDTA chelation), validated outcome (lack of reliance on self-report/recall), control of confounding [0.5 points for inclusion of age, sex, race/field center (if multi-ethnic cohort), BMI, smoking, alcohol, physical activity; 0.5 points for adjustment of fiber in dietary magnesium models; 0.5 points for adjustment of diabetes at baseline in circulating magnesium models], and analysis (1 point if risk estimate determination and statistical approaches were appropriate for the study design). Scores were summed; studies with scores from 0 to 3 and 4 to 6 were considered to be of lower and higher quality, respectively.
For Khan et al (20), categorical estimates were used for generalized least-squares trend, because the published continuous estimate for a 0.2-mmol/L dose (RR: 0.55; 95% CI: 0.10, 2.98) was strongly influenced by the presence of a small number of outlying hypomagnesemic individuals (serum magnesium <0.62 mmol/L) who were at markedly elevated CVD risk (RR: 1.99; 95% CI: 1.02, 3.85) compared with the reference group with normal magnesium concentrations (0.62–0.91 mmol/L).