Women who smoke have a 25% greater risk for coronary heart disease (CHD) then men who smoke, compared with nonsmokers, data from a meta-analysis involving more than 2.4 million people indicate.

The increased risk was independent of other cardiovascular risk factors, according to study researchers Rachel R. Huxley, DPhil, of the University of Minnesota in Minneapolis, and Mark Woodward, PhD, of Johns Hopkins University in Baltimore.

Although the exact cause of the sex difference in CHD risk among men and women is unclear, the researchers noted that the relative risk increased 2% with each additional year of follow-up, suggesting that pathophysiological factors may play a role.

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“For example, women might extract a greater quantity of carcinogens and other toxic agents from the same number of cigarettes than men. This occurrence could explain why women who smoke have double the risk of lung cancer compared with their male counterparts,” they wrote.

The analyses included data from 3,912,809 individuals who participated in 86 cohort studies. All studies were conducted between 1996 and 2010 and had a mean follow-up of 40 years. A total of 67,075 fatal and nonfatal CHD events occurred.

In one analysis involving 2.4 million people that adjusted for cardiovascular risk factors other than CHD, women who smoked had a 1.25 relative risk of developing coronary artery disease compared with men (95% CI: 1.12-1.39; P<0.0001).

Data from another analysis involving 3.3 million people indicated that the age-adjusted relative risk for fatal and nonfatal CHD was greater for women than men (RR=1.11; 95% CI: 1.12 to 1.39, P<0.0001).

These results remained significant after the researcher adjusted for potential publication bias.

Huxley and Woodward also examined the risk by varying age groups in the 30 to 60 year range. They determined that women in every age group except those 30 to 44 years had a greater risk for CHD than men, but that the differences was only statistically significant in women 60 to 69 years.

“What makes the realization that women are at increased risk worrisome is that the tobacco industry views women as its growth market,” wrote Matthew A Steliga, MD, and Carolyn M. Dresler, MD, both from the University of Arkansas in Little Rock, in an accompanying editorial.

They emphasized the importance of including women in smoking cessation efforts. “Although more men than women smoke, those women who do smoke have a greater risk of CHD and therefore targeting of both sexes is imperative for smoking prevention and cessation on a global, national and individual basis,” they added.

The researchers noted the following study limitations: lack of standardization for dose and duration of  smoking, inability to adjust for oral contraceptive use and varied definitions of “nonsmokers” among study cohorts.

Huxley R. et al. Lancet. 2011;doi: 10.1016/S0140- 6736(11)60781-2.

Steliga M et al. Lancet. 2011;doi: 10.1016/S0140-6736(11)60781-2.