Stroke is one of the leading causes of disability and death in many countries across all levels of economic development. An estimated 15 million new cases of stroke occur worldwide annually. Stroke contributes to approximately 10% of total deaths globally (1), and the incidence of stroke is likely to increase during the next 20 years (2). Ischemic stroke accounts for more than 70% of all stroke cases in Western countries and approximately 60% of cases in China (3,4).

Various foods and nutrients are associated with the risk of stroke (5). A diet rich in potassium, calcium, and magnesium may reduce the risk of stroke, whereas decreasing sodium intake can lower blood pressure and stroke risk (6-8). The effect of iron intake is less clear (9). Because minerals are essential elements for the human body, epidemiologic studies have investigated the relationship between ischemic stroke and dietary mineral consumption, but the results are inconsistent (9-17). Moreover, to our knowledge, no published studies have investigated this issue in the southern Chinese population. In view of the limited and emerging evidence, we aimed to ascertain whether the dietary intake of these minerals is associated with the risk of ischemic stroke for southern Chinese adults. The study was part of a research project assessing the role of nutrition and lifestyle factors for the prevention of this major chronic disease.

The mean age (approximately 69 y) and BMI of case patients and control patients were similar (Table 1). The prevalence of hypertension, diabetes, and current smoking was higher among case patients than control patients. Case patients also had higher cumulative smoking exposure, and were less physically active over their life course than control patients.

Case patients' mean dietary intakes of potassium, calcium, and magnesium were significantly lower (P < .001) than those of control patients, whereas sodium intake in the 2 groups was similar. Although iron levels were higher among women in the control group than among women in the case group, the corresponding mean difference in men was not significant.

Stroke risk was inversely associated with higher weekly dietary calcium and magnesium levels (Table 2). The adjusted odds ratio (OR) for both minerals was 0.32 for the highest category of intake compared with the lowest category. No significant associations were found for potassium, iron, or sodium.

Sodium intake from the food assessment was positively associated with participants' self-rated sodium intake, which ranged from a mean (standard deviation [SD]) of 5,586 (SD, 3,998) mg/week to 7,967 (SD, 6,115) mg/week. Approximately one-third of stroke patients described their diet as high in salt. The stroke risk was more than twofold for Chinese adults on a diet high in salt compared with those who described their diet as low in salt, even after controlling for confounding demographic and lifestyle variables and total energy intake (Table 3). Proxy information was used in 22% of the cases.

We found inverse associations between ischemic stroke risk and dietary intake of calcium, magnesium, and potassium by southern Chinese adults, together with significant dose-response relationships for calcium and magnesium. An inverse association was also found for potassium but did not reach significance. However, regarding sodium intake, the risk of stroke more than doubled for study participants who self-reported a diet high in salt, suggesting the adverse effect of added salt and soy sauce during cooking.

High sodium intake has been linked to high blood pressure (26), unlike potassium, calcium, and magnesium, which have demonstrated beneficial effects (12,27-30). Nevertheless, previous results concerning the association between sodium intake and risk of stroke have been mixed (13,15,16). In addition to differences in sodium consumption levels, variations in underlying population characteristics, cooking methods, exposure measurements, and genetic disparity among studies also contribute to the inconsistencies.

The observed protective effects of calcium and magnesium appear to be consistent with findings from cohort studies conducted in the United States (10,14,31-33), Finland (15), and Japan (34). The role of potassium in stroke risk is unclear on the basis of our literature review (14,15,31,32).

Our results suggest that increased iron intake may elevate stroke risk. It has been hypothesized that higher iron stores could increase the risk of atherosclerotic cardiovascular disease (35). In contrast, a recent cross-sectional study involving 4 countries reported a significant inverse association between iron intake and blood pressure (36), whereas a randomized clinical trial observed no effect of reducing iron stores through phlebotomy on the risk of stroke and myocardial infarction after 6 years of intervention (37). Therefore, further investigation on the effect of dietary iron level is required.

This study has several strengths. It was the first to our knowledge to investigate the association between dietary mineral intake and ischemic stroke risk in southern China. The reference period for dietary exposure was set at 1 year before interview to avoid possible dietary change as a consequence of stroke. The sample size of 838 participants ensured sufficient power for the multivariable analysis. We included only first-ever ischemic stroke patients with diagnosis confirmed by brain image. All control patients were screened for stroke symptoms by a neurologist to ensure correct classification of their disease status. Moreover, the 3 participating hospitals served the entire Foshan catchment region so that our participants were representative of the target population.

Several limitations should be taken into account. First, salt consumption was difficult to quantify and was excluded in the calculation of sodium intake. Nevertheless, a salty diet was separately associated with a higher risk of stroke for Chinese adults, which supported the evidence based on dietary sodium intake. Second, only 5 major minerals derived from the Chinese diet were available from the nutrient database (25). Consequently, effects of other minerals such as phosphorus and zinc could not be evaluated.

Because of the retrospective study design, recall bias is possible. A major weakness concerned the accuracy of mineral intake. Our results were based on recall of dietary behaviors with a reference period of 12 months and relied on estimates of intake of dietary minerals that were not verified by using biomarkers. Although we assessed the typical diet using a validated and reliable food frequency questionnaire for the southern Chinese population, the self-reported information was subject to measurement errors. Face-to-face interviews were conducted in the presence of case patients' next-of-kin to improve interpretation and accuracy. Moreover, the primary author (W.L.) conducted all interviews to eliminate inter-interviewer bias. Control patients were recruited during the same period and from the same catchment area as were case patients. They should therefore provide comparable estimates of foods intake. But the inherent selection bias was unavoidable because of their voluntary participation in the study. Proxy information was used in 22% of the cases, yet we found no significant differences between index patients and their proxies on weekly intake of minerals. Information bias was unlikely, because the potential effects of dietary minerals have not been established in China and all participants were blinded to the study hypothesis. Nevertheless, residual confounding might be present even though we controlled for plausible confounding factors in the multivariable analyses.

The findings of this study suggest that lowering sodium intake while maintaining high levels of dietary calcium and magnesium may be beneficial to prevent ischemic stroke for Chinese adults. Prospective cohort studies that collect detailed dietary exposure information are recommended to confirm the observed effects of these minerals in other populations.