Heterogeneous associations between smoking and a wide range of initial presentations of cardiovascular disease in 1937360 people in England: lifetime risks and implications for risk prediction

Abstract

Background: It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation.

Methods: Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997-2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme).

Results: During 11.6 million person-years of follow-up, 114859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers' lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR)=1.04, 95% confidence interval (CI) 0.91-1.19).The strength of association differed markedly according to disease type: stable angina (HR=1.08, 95% CI 1.01-1.15),transient ischaemic attack (HR=1.41, 95% CI 1.28-1.55), unstable angina (HR=1.54, 95% CI 1.38-1.72), intracerebral haemorrhage (HR=1.61, 95% CI 1.37-1.89), heart failure (HR=1.62, 95% CI 1.47-1.79), ischaemic stroke (HR=1.90, 95% CI 1.72-2.10), MI (HR=2.32, 95% CI 2.20-2.45), SAH (HR= 2.70, 95% CI 2.27-3.21), PAD (HR=5.16, 95% CI 4.80-5.54) and abdominal aortic aneurysm (AAA) (HR=5.18, 95% CI 4.61-5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR=1.36, 1.47 and 2.74, respectively).

Conclusions: The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction.

Keywords: Association study; cardiovascular outcomes; epidemiology; initial presentation; lifetime risks; primary prevention; risk prediction; risk stratification; smoking.

Figure 1.

Lifetime cumulative incidence of 12 CVD phenotypes stratified by baseline smoking status. Shaded areas indicate confidence intervals.

Figure 2.

Age-adjusted hazard ratios of 12 CVDs comparing current vs never smokers. Cardiac arrest/SCD, cardiac arrest, ventricular fibrillation and sudden cardiac death; CI, confidence interval; HR, hazard ratio derived from Cox proportional hazard models with baseline hazard function stratified by sex and general practice and adjusted for baseline age (linear and quadratic terms); MI, myocardial infarction. The vertical dotted line indicates the HR of the composite cardiovascular disease endpoint.

Figure 3.

Age-adjusted hazard ratios of 12 CVDs comparing current vs never smokers in men and women. Cardiac arrest/SCD, cardiac arrest, ventricular fibrillation and sudden cardiac death; CI, confidence interval; HR, age-adjusted hazard ratio from Cox proportional hazard models with baseline hazard function stratified by general practice and adjusted for baseline age (linear and quadratic terms). *P-value for interaction ≤0.05 (P = 0.05 for myocardial infarction and P = 0.0005 for peripheral arterial disease).

Figure 4.

Population-attributable fractions (%) for 12 CVDs associated with current smoking in men and women. Cardiac arrest/SCD, cardiac arrest, ventricular fibrillation and sudden cardiac death; CI, confidence interval; CVD, cardiovascular diseases; PAF, population-attributable fraction derived from Cox proportional hazard models with baseline hazard function stratified by sex and general practice and adjusted for baseline age (linear and quadratic terms).

Figure 5.

Age-adjusted hazard ratios of 12 CVDs for duration of smoking cessation vs current smokers. Cardiac arrest/SCD, cardiac arrest, ventricular fibrillation and sudden cardiac death; CI, confidence interval; HR, hazard ratio derived from Cox proportional hazard models with baseline hazard function stratified by sex and general practice and adjusted for baseline age (linear and quadratic terms).

Figure 6.

Increment in c-index associated with inclusion of smoking status in CVD phenotype-specific models containing sex and age. The vertical bold line indicates the increment in the c-index estimate for the CVD composite (increment index = 0.016, 95% CI 0.015-0.017), compared with a sex- and age-adjusted model with c-index = 0.73 (95% CI 0.72-0.73). Cardiac arrest/SCD, cardiac arrest, ventricular fibrillation and sudden cardiac death; CHD, coronary heart disease; CI, confidence interval; CVD, cardiovascular diseases.