Background--National Cholesterol Education Program Adult Treatment Panel III guidelines recommend therapeutic lifestyle changes (TLC) and drug therapy to reduce cardiovascular disease (CVD) risk. These guidelines have been revised recently (ATP III-R); however, the risk of CVD mortality within each intervention window and the effects of cardiorespiratory fitness (CRF) and metabolic syndrome on CVD mortality within the framework of the guidelines are unknown.

Methods and Results--Risk factor and CRF data from 19 125 men (aged 20 to 79 years) who attended a preventive medical clinic between 1979 and 1995 were used. Mortality follow-up was completed until December 31, 1996. Participants were assigned to ATP III-R groups (LDL-C goal, TLC initiation, and drug consideration), and risk of CVD mortality was assessed by Cox proportional hazards regression. There were 179 CVD deaths over an average 10.2 years of follow-up. Compared with the LDL-C goal group, men in the TLC initiation and drug consideration groups had an elevated risk of CVD mortality (TLC initiation: HR=2.65, 95% CI 1.67 to 4.19; drug consideration: HR=6.44, 95% CI 4.49 to 9.25). Compared with LDL-C goal/fit, CVD mortality risk was higher in the LDL-C goal/unfit (4.8, 2.5 to 9.1), TLC initiation/fit (3.0, 1.7 to 5.3), TLC initiation/unfit (7.5, 3.7 to 15.2), drug consideration/fit (7.2, 4.6 to 11.4), and drug consideration/unfit (14.9, 9.1 to 24.4) groups. A similar gradient was observed for metabolic syndrome across intervention windows.

Conclusions--Men eligible for TLC or drug consideration under ATP III-R were at elevated risk of CVD mortality compared with men who met the LDL-C goal. Furthermore, men who were physically fit or who did not have the metabolic syndrome had a lower risk of CVD mortality.