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Title: Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland

Authors:  Nyssonen K, Parviainen MT, Salonen R, et.al.

Reference:  BMJ 1997;314:634-8

Summarized by: Max A. Luna

Summary: The oxidation of low-density lipoprotein (LDL) has been implicated in atherogenesis and in the progression of early coronary plaques. Vitamin C, vitamin E and beta-carotene are antioxidants that have been considered potential agents for inhibiting oxidation of LDL, and therefore having a possible role in prevention of coronary artery disease.  Prior studies have had conflicting results in the study of antioxidants and the risk of coronary artery disease.  None of these studies have considered the role of vitamin C deficiency.

This study examined the association of vitamin C deficiency with the risk of myocardial infarction in middle-aged men free of coronary disease from eastern Finland. It followed a prospective cohort of 1605 men ages 42, 48, 54 and 60 free of coronary artery disease.  Interview, Physical exam, resting electrocardiogram, exercise testing and blood/serum analysis were performed at entry.  The sample was divided in two groups, based on serum levels of Vitamin C. Vitamin C deficiency group had less than or equal to 11.4 micromols/liter and normal vitamin C group had above 11.4 micromols/liter.

Follow-up period was an average of five years and maximum of 8.75 years.  Fatal and non-fatal myocardial infarction were monitored by a registry that collected detailed diagnostic information of all such attacks in the study cohort in a prospective manner between 1984 to 1992.

Baseline variables considered were: age, smoking (active and amount), socioeconomic status, maximal oxygen uptake, dietary carotene, iron, coffee, alcohol, physical activity, systolic blood pressure, serum LDL and triglycerides and HDL, serum apolipoprotein B, diabetes, hair mercury content. Significant difference in baseline characteristics were present between the two study groups, these were: age, smoking, adult socioeconomic status, maximal oxygen uptake, dietary carotene, blood leukocyte, dietary iron, moderate to vigorous activity, systolic blood pressure, alcohol intake and coffee intake; all favoring the group with normal vitamin C.

Men who had vitamin C deficiency were at increased risk of myocardial infarction during follow up.  Relative risk was 4.0 (95% confidence interval of 1.7 to 9.4 (P=.0012). Risk of MI was 13.2 % in the vitamin C deficiency group vs. 3.8% in the normal vitamin C group.

After adjusting for age, year of examination and season of the year, the strongest predictors of MI were maximal oxygen uptake, the number of pack years of cigarettes smoked, blood leukocyte count and low plasma vitamin C concentration. There was a slow average increase in the mean plasma vitamin C concentration during the six years of baseline examinations.  For this reason the year of examination was adjusted for in all statistical analyses.

When all coronary risk factors were controlled, vitamin C deficiency had a relative risk of myocardial infarction of 2.5 (1.3 to 5.2 P=.0095) compared with those with higher.

Discussion: Vitamin C is considered to be the most effective antioxidant in human plasma.  It is thought to be the first antioxidant to be used up during lipid peroxidation, constituting a rate-limiting factor for oxidation of lipids.  This study suggests that vitamin C deficiency is an independent risk factor for myocardial infarction.

As in this study, confounding can be a major limitation in all non-experimental studies. As described in the baseline characteristics of the two groups, important coronary risk factors where different at entry favoring the group with normal levels of vitamin C.  When controlling for these differences, the risk ratio for MI in the low vitamin C decreased from 4.0 to 2.6, remaining statistically significant. However, some unmeasured factors might have confounded the relation between vitamin C concentration and the risk of MI even after controlling for all different variables.

No randomized control study has been done studying the effect of vitamin C supplementation in the risk of myocardial infarction.  Prospective cohorts have been published revealing no effect of vitamin C supplementation in primary prevention of MI. Based on these prior studies and the results of this study, vitamin C supplementation may only be beneficial for prevention of MI on patients that have vitamin C deficiency.