Current issues of ACP Journal Club are published in Annals of Internal Medicine


Low vitamin E levels increased the risk for angina pectoris in men

ACP J Club. 1991 May-June;114:92. doi:10.7326/ACPJC-1991-114-3-092

Source Citation

Riemersma RA, Wood DA, Macintyre CC, et al. Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene. Lancet. 1991Jan 5;337:1-5.



To determine if plasma concentrations of vitamins with antioxidant properties are associated with the risk for angina, independent of classic risk factors for coronary heart disease.


Case-control study.


Population-based study in Edinburgh, Scotland, United Kingdom.


A systematic sample of 6000 men aged 35 to 54 years listed in the Lothian Health Board Central Register with an address in the city of Edinburgh was surveyed. Men who answered positively to a chest pain questionnaire but had not seen a doctor for these symptoms were considered to be case patients. Control patients were matched for age and sex, were drawn from the same population, answered negatively to the chest pain questionnaire, and had no history of coronary heart disease. 125 cases of angina pectoris (response rate 83%) and 430 healthy controls (response rate 76%) had a medical assessment.

Assessment of risk factors

Complete vitamin data were obtained for 110 cases and 394 controls during the medical assessment. Levels of vitamins A, C, and E and carotene were measured. Odds ratios [ORs] for angina were calculated in relation to the distribution of vitamin concentrations in the healthy control population.

Main outcome measure

Presence or absence of angina pectoris determined by positive or negative replies to the World Health Organization Chest Pain Questionnaire.

Main results

The adjusted OR for angina in the lowest quintile of vitamin E distribution was 2.68 (95% CI 1.07 to 6.70, P = 0.02). The unadjusted OR for angina in the lowest concentrations of vitamin C and carotene were 2.35 (CI 1.16 to 4.78) and 2.64 (CI 1.32 to 5.29), respectively, but were not significant after adjustment for smoking and other risk factors (P = 0.09 and P = 0.40, respectively). No significant relation was found with vitamin A.


In this population case-control study, low plasma levels of vitamin E were related to an increased risk for angina pectoris in men after adjustment for age, blood pressure, total and high-density lipoprotein cholesterol, nonfasting triglycerides, relative weight, and smoking status.

Sources of funding: The British Heart Foundation; the Wellcome Trust; Scottish Home and Health Department; Scottish Chest Heart and Stroke Association.

Address for article reprint: Dr. R.A. Riemersma, Cardiovascular Research Unit, University of Edinburgh, George Square, Edinburgh EH8 9XF, Scotland, UK.


Clinicians and epidemiologists have postulated a relation between vitamin levels and the risk for several chronic diseases such as cancer and cardiovascular disease. These relations have been explored using observational evidence, usually beginning with case-control studies. These studies often record modest ORs as evidence of a risk or causal relation.

Riemersma and colleagues used similar methods and found similar results. To determine the clinical usefulness of the implied causal relation, an intervention study aimed at reducing the risk for cardiovascular disease would be required, as the authors of this study clearly point out.

Evidence from an intervention trial may come from the Physicians' Health Study, a randomized, controlled, double-blind trial using a factorial design to assess the effect of aspirin on cardiovascular disease and of β-carotene on cancer (1). The original trial design was not intended to study the relation between β-carotene and cardiovascular disease; however, preliminary data derived from the study, using a subgroup of 333 men who already had angina or coronary revascularization before randomization, showed a protective effect of β-carotene on a combined end point of all major coronary events (relative risk 0.56, P = 0.05) (2). The investigators of the Physicians' Health Study intend to examine this relation further when the study is completed, recognizing that caution must be used in interpreting a result based on a data-derived hypothesis (Hennekens CH. Personal communication). The clinical significance of the study by Riemersma and colleagues must await further results of intervention studies.

Allan S. Detsky, MD, PhD
University of TorontoToronto, Ontario, Canada


1. Steering Committee of the Physicians' Health Study. Final report of the aspirin component of the ongoing Physicians' Health Study. N Engl J Med. 1989;321:129-36.

2. Gaziano JM, Manson JE, Ridker PM, et al. Beta carotene therapy for chronic stable angina. Circulation. 1990;82(Suppl. III):201.


Important new epidemiologic studies confirm the epidemiologic association between low vitamin E levels and cardiovascular risk (3-5). The large negative trials of β-carotene and the equivocal vitamin E trials have also been published (6-11)

Eva Lonn, MD
McMaster UniversityHamilton, Ontario, Canada

3. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;328:1444-9.

4. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328:1450-6.

5. Jha P, Flather M, Lonn E, Farkouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease. A critical review of epidemiologic and clinical trial data. Ann Intern Med. 1995;123:860-72.

6. The Alpha-Tocopherole, β-carotene Cancer Prevention Study Group. The effect of vitamin E and β-carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029-35.

7. Blot WJ, Li JY, Taylor PR, et al. Nutritional intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst. 1993;85:1483-92.

8. Stephens NG, Parsons A, Schofield PM, et al. Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347:781-6.

9. Hennekens CH, Buring JE, Manson JE, et al. Lack of long-term supplementation with β-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996;334:1145-9.

10. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of β-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996;334:1150-5.

11. Greenberg ER, Baron JA, Karagos MR, et al. Mortality associated with low plasma concentration of β-carotene and the effects of oral supplementation. JAMA. 1996;275:699-703.