1836 VOLUME 18 NUMBER 9 | SEPTEMBER 2010 | www.obesityjournal.org ARTICLES nature publishing group EPIDEMIOLOGY INTRODUCTION Obesity is a major health problem with increasing prevalence over the past several decades (1,2). Obesity, as conventionally deined by relative weight, has been associated with signiicant morbidity including type 2 diabetes mellitus, hypertension (HTN), dyslipidemia, and cardiovascular disease. However, obesity is heterogeneous, i.e., not all obese patients develop cardiometabolic complications. he BMI is the most frequently used marker for relative weight. However, the BMI does not distinguish between adi- pose and lean tissue, and has not proven to be a predictor of cardiovascular events (3) or mortality (4) in some large cohorts. Furthermore, excessive fat accumulation in patients with normal BMI is also associated with deleterious efects (5,6). Visceral fat accumulation is associated with deleterious metabolic and cardiovascular consequences. Viscerally obese subjects have higher insulin and triglycerides (TGs) levels, and lower high-density lipoprotein-cholesterol (HDL-C) levels compared with lean or obese subjects without visceral fat accu- mulation (7–9). Despres et al. were the irst to introduce the concept of “hypertriglyceridemic waist” (HyperTG-Waist) and showed that men with waist circumference (WC) >90 cm and fasting TG >2 mmol/l had excess visceral fat, increased insulin and apolipoprotein B levels, and increased small LDL parti- cle number (10). An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), com- putes the WC and fasting TG concentration as follows: LAP = (WC (cm) − 65) × TG (mmol/l) for men and (WC − 58) × TG for women (11). Cross-sectional analysis of the third National Health and Nutrition Examination Survey III (NHANES III) cohort showed that higher LAP, as compared with BMI, was associated with higher low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B, and uric acid levels, higher total cholesterol/HDL-C and apolipoprotein B/apolipoprotein A1 The Lipid Accumulation Product and All-cause Mortality in Patients at High Cardiovascular Risk: A PreCIS Database Study Adriana G. Ioachimescu 1,2 , Danielle M. Brennan 3 , Brian M. Hoar 4 and Byron J. Hoogwerf 4–6 The BMI is the most frequently used marker to evaluate obesity-associated risks. An alternative continuous index of lipid over accumulation, the lipid accumulation product (LAP), has been proposed, which is computed from waist circumference (WC, cm) and fasting triglycerides (TGs) (mmol/l): (WC - 65) × TG (men) and (WC - 58) × TG (women). We evaluated LAP and BMI as predictors of mortality in a high-risk cohort. Study population included 5,924 new consecutive patients seen between 1995 and 2006 at a preventive cardiology clinic. Fifty-eight percent of patients were discordant for their LAP and BMI quartiles. Patients whose LAP quartile was greater than BMI quartile had higher mortality compared with those with LAP quartile was lower than BMI quartile (8.2 vs. 5.4% at 6 years, P = 0.007). After adjustment for age, gender, smoking, diabetes mellitus, blood pressure, low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), (ln)LAP was independently associated with mortality (hazard ratio (HR) = 1.46, P < 0.001). BMI was not associated with increased mortality (HR = 1.06, P = 0.39). Adding LAP to a model including traditional risk factors for atherosclerosis increased its predictive value (C statistic 0.762 vs. 0.750, P = 0.048). Adding BMI to the same model did not change its predictive value (0.749 vs. 0.750, P = 0.29). Subgroup analyses showed that LAP predicted mortality in the nondiabetic patients (adjusted HR for (ln)LAP 1.64, P < 0.001), but did not reach significance in the diabetic patients (HR = 1.21, P = 0.11). In conclusion, LAP and not BMI predicted mortality in nondiabetic patients at high risk for cardiovascular diseases. LAP may become a useful tool in clinical practice to stratify the risk of unfavorable outcome associated with obesity. Obesity (2010) 18, 1836–1844. doi:10.1038/oby.2009.453 1 Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA; 2 Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA; 3 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA; 4 Department of Preventive Cardiology and Rehabilitation, Cleveland Clinic, Cleveland, Ohio, USA; 5 Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, Cleveland, Ohio, USA; 6 Present address: Lilly USA, Endocrinology-Diabetes, Indianapolis, Indiana, USA. Correspondence: Adriana G. Ioachimescu (aioachi@emory.edu) Received 31 March 2009; accepted 1 November 2009; published online 24 December 2009. doi:10.1038/oby.2009.453