Death from pulmonary thromboembolism in severe obesity: lack of association with established genetic and clinical risk factors

Several clinical and environmental conditions are causally related to sudde n death from acute pulmonary thromboembolism (APT). Morbid obesity, despite its frequency and association with adverse health effects, is usually cons idered at most only an additive risk factor for APT. We reviewed protocols and histories from 7227 consecutive autopsies performed between 1985 and 19 96 at the Mayo Clinic, including all deaths from APT where no clinical or e nvironmental risk factor could be identified in the study. Body mass indice s (BMI) were calculated and compared with those of age- and sex-matched con trols who had died suddenly and naturally without evidence of APT. Resistan ce to activated protein C is the most common molecular clotting defect pred isposing to APT, and it is caused by a point mutation in the factor V gene (R(506)Q). Genomic DNA was extracted from archival tissues of all cases and controls, and the R(506)Q status was determined by polymerase chain reacti on amplification, restriction endonuclease digestion, and direct sequencing . APT was found as the immediate cause of death in 433 patients, with 36 (8 %) having no previously established risk factors. Twenty-four of these pers ons (67%) were morbidly obese (BMI >30 kg/m(2)), compared with only five co ntrols (14%, P<0.0001). Four patients in both groups, each with a BMI <30 k g/m(2), had at least one allele positive for R(506)Q. Morbid obesity is an independent risk factor in cases of sudden death from APT after the exclusi on of previously established clinical, environmental, and molecular risk fa ctors.