Smokeless Tobacco Use: A Risk Factor for Hyperhomocysteinemia in a Pakistani Population

BACKGROUND Smokeless tobacco (ST) use is highly prevalent in the South Asian populations. While there have been a number of reports on association of ST consumption with cancer, very few studies have been conducted to investigate its relationship with cardiovascular disease. Hyperhomocysteinemia is a well-recognized risk factor for cardiovascular disease; however, its association with ST use has never been investigated. The objective of this study was to evaluate the relationship of ST use with hyperhomocysteinemia in an urban Pakistani population. METHODOLOGY/PRINCIPAL FINDINGS In a cross-sectional study for assessment of risks of hyperhomocysteinemia, 872 healthy adults (355 males and 517 females of age range 18-60 years) were recruited from a low-income population in Karachi, Pakistan. A detailed questionnaire was administered which included information about smoking, non-smoking, use of ST alone (chewing as well as sniffing) and use of ST with betel nuts. Fasting serum/plasma levels of homocysteine, folate, vitamin B12 and pyridoxal phosphate (PLP; a coenzymic form of vitamin B6) were analyzed. In this population, 43.4% males and 15.5% females were found to be regular users of ST products. Laborers and vendors were the major ST consumers. Smoking was not found to be associated with plasma/serum concentrations of homocysteine, folate, vitamin B12 and PLP. However, homocysteine concentrations in the group which consumed ST alone and the group which consumed ST along with betel nut were significantly higher compared to the non-user group (17.7±7.5 µmol/L, 25.48 µmol/L vs. 11.95 µmol/L, respectively; p<0.01). Odds ratio for the association of hyperhomocysteinemia (>15 µmol/L) was 11-fold higher in the ST-consumer group compared to the non-user group, [OR (95%CI)  = 11.34 (7.58-16.96); p<0.001], when the model was adjusted for age, gender, folate and vitamin B12 status. CONCLUSION This study shows a positive association between ST consumption and hyperhomocysteinemia in a low-income urban Pakistani population.