G-ESTIMATION OF CAUSAL EFFECTS - ISOLATED SYSTOLIC HYPERTENSION AND CARDIOVASCULAR DEATH IN THE FRAMINGHAM HEART-STUDY

Time-dependent covariates are often both confounders and intermediate variables. In the presence of such covariates, standard approaches for adjustment for confounding are biased. The method of G-estimation all ows for appropriate adjustment. Previous studies applying the G-estima tion method have addressed effects on all-cause mortality rather than on specific causes of death. In the present study, a method to adjust for censoring by competing risks is presented, The authors used the ap proach to estimate the causal effect of isolated systolic hypertension on cardiovascular mortality in the Framingham Heart Study, with a 10- year follow-up using data from 1956 to 1970. Arterial rigidity is a ma jor determinant of isolated systolic hypertension and may be a confoun der of the relation between isolated systolic hypertension and cardiov ascular death. Conversely, isolated systolic hypertension may by itsel f contribute to stiffening of the vessel wall, and arterial rigidity m ay therefore also be an intermediate variable in the causal pathway fr om isolated systolic hypertension to cardiovascular death. While contr olling for arterial rigidity and other baseline and time-dependent cov ariates, isolated systolic hypertension decreased the time to cardiova scular death by 45% (95% confidence interval 3-69).