Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports

Abstract

Objective: To use the relation between cigarette consumption and cardiovascular disease to quantify the risk of coronary heart disease and stroke for light smoking (one to five cigarettes/day).

Design: Systematic review and meta-analysis.

Data sources: Medline 1946 to May 2015, with manual searches of references.

Eligibility criteria for selecting studies: Prospective cohort studies with at least 50 events, reporting hazard ratios or relative risks (both hereafter referred to as relative risk) compared with never smokers or age specific incidence in relation to risk of coronary heart disease or stroke.

Data extraction/synthesis: MOOSE guidelines were followed. For each study, the relative risk was estimated for smoking one, five, or 20 cigarettes per day by using regression modelling between risk and cigarette consumption. Relative risks were adjusted for at least age and often additional confounders. The main measure was the excess relative risk for smoking one cigarette per day (RR_{1_per_day}-1) expressed as a proportion of that for smoking 20 cigarettes per day (RR_{20_per_day}-1), expected to be about 5% assuming a linear relation between risk and consumption (as seen with lung cancer). The relative risks for one, five, and 20 cigarettes per day were also pooled across all studies in a random effects meta-analysis. Separate analyses were done for each combination of sex and disorder.

Results: The meta-analysis included 55 publications containing 141 cohort studies. Among men, the pooled relative risk for coronary heart disease was 1.48 for smoking one cigarette per day and 2.04 for 20 cigarettes per day, using all studies, but 1.74 and 2.27 among studies in which the relative risk had been adjusted for multiple confounders. Among women, the pooled relative risks were 1.57 and 2.84 for one and 20 cigarettes per day (or 2.19 and 3.95 using relative risks adjusted for multiple factors). Men who smoked one cigarette per day had 46% of the excess relative risk for smoking 20 cigarettes per day (53% using relative risks adjusted for multiple factors), and women had 31% of the excess risk (38% using relative risks adjusted for multiple factors). For stroke, the pooled relative risks for men were 1.25 and 1.64 for smoking one or 20 cigarettes per day (1.30 and 1.56 using relative risks adjusted for multiple factors). In women, the pooled relative risks were 1.31 and 2.16 for smoking one or 20 cigarettes per day (1.46 and 2.42 using relative risks adjusted for multiple factors). The excess risk for stroke associated with one cigarette per day (in relation to 20 cigarettes per day) was 41% for men and 34% for women (or 64% and 36% using relative risks adjusted for multiple factors). Relative risks were generally higher among women than men.

Conclusions: Smoking only about one cigarette per day carries a risk of developing coronary heart disease and stroke much greater than expected: around half that for people who smoke 20 per day. No safe level of smoking exists for cardiovascular disease. Smokers should aim to quit instead of cutting down to significantly reduce their risk of these two common major disorders.

Fig 1

Relative risk for coronary heart disease for men smoking one cigarette per day. IV=inverse variance. Studies are in reference numbers 16-70. Excluding five studies that used relative risks instead of hazard ratios increased pooled relative risk (to 1.53)

Fig 2

Distribution of excess relative risk for smoking one or five cigarettes per day, each in relation to smoking 20 per day, using within study results (horizontal dashes show median). For example, in Lawlor et al (2008), estimated relative risk for coronary heart disease (CHD) was 1.83 or 2.63 for those smoking one or 20 per day, respectively (from regression analysis of this study). Proportion of excess relative risk associated with one cigarette per day is therefore 51%: (1.83−1)/(2.63−1), which is plotted. (A negative value is when relative risk for one (or five) per day is <1.0.) For CHD in men, one study (Wen et al 2004) reported decreasing relative risks for increasing consumption for ≥65 age group, which appears as excess relative risk percentage of >100% (for completeness these are kept in, but do not affect median value)

Fig 3

Relative risk for coronary heart disease for women smoking one cigarette per day. IV=inverse variance. Studies are in reference numbers 16-70. Excluding two studies that used relative risks instead of hazard ratios slightly increased pooled relative risks (to 1.63).

Fig 4

Relative risk for stroke for smoking one cigarette per day in men (top) and women (bottom). Studies are in reference numbers 16-70. IV=inverse variance. Excluding four studies in men and one study in women that used relative risks instead of hazard ratios slightly increased pooled relative risks to 1.28 for men and 1.34 for women