Excess abdominal fat raised the risk of cardiovascular disease by 44% compared with fat located elsewhere on the body.
Researchers said the findings support growing acknowledgment of the importance of ectopic fat in cardiovascular disease.
The study by the Brigham and Women's Hospital in Boston, Massachusetts was the first to use CT scans to study specific fat deposits to compare direct links with risk of cardiovascular disease, cancer and death.
Researchers assessed levels of excess fat around the abdomen, heart tissue and the aortic artery in 3,086 patients and followed up after seven years. The average age was 50 and almost half were women.
They detected 90 cardiovascular events, 141 cancers and 71 deaths. After accounting for risk factors and general obesity, abdominal fat posed a far greater risk of heart disease and cancer than other fat deposits, although none were linked to an added risk of death.
Authors suggested waist circumference may be a surrogate marker of visceral fat, which has been linked to cardiovascular disease.
Lead author Kathryn Britton said: 'Given the worldwide obesity epidemic, identification of high-risk individuals is important, as it allows targeting of preventive and therapeutic measures.'