Abdominal fat mass is strongly independently associated with CVD risk factors in the present study. In contrast, gynoid fat mass was positively associated, whereas the ratio of gynoid to total fat mass was negatively associated with risk factors for CVD.

lean mass is associated strongly with survival in older subjects. Greater fat mass is protective in older women, whereas very low or very high fat mass increases the risk of death in men. Further research is needed to better understand the mechanisms underlying these associations.

In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730 +/- 30 vs 330 +/- 65 arbitrary units, p < 0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-alpha; 460 +/- 110 vs 133 +/- 8 arbitrary units, p < 0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.

Objective: The relationships between objectively measured abdominal and gynoid adipose mass with the prospective risk of myocardial infarction (MI) has been scarcely investigated. We aimed to investigate the associations between fat distribution and the risk of MI. Subjects: Total and regional fat mass was measured using dual-energy X-ray absorptiometry (DEXA) in 2336 women and 922 men, of whom 104 subsequently experienced an MI during a mean follow-up time of 7.8 years.Results: In women, the strongest independent predictor of MI was the ratio of abdominal to gynoid adipose mass (hazard ratio (HR) ¼ 2.44, 95% confidence interval (CI) 1.79-3.32 per s.d. increase in adipose mass), after adjustment for age and smoking. This ratio also showed a strong association with hypertension, impaired glucose tolerance and hypertriglyceridemia (Po0.01 for all). In contrast, the ratio of gynoid to total adipose mass was associated with a reduced risk of MI (HR ¼ 0.57, 95% CI 0.43-0.77), and reduced risk of hypertension, impaired glucose tolerance and hypertriglyceridemia (Po0.001 for all). In men, gynoid fat mass was associated with a decreased risk of MI (HR ¼ 0.69, 95% CI 0.48-0.98), and abdominal fat mass was associated with hypertriglyceridemia (P for trend 0.02). Conclusion: In summary, fat distribution was a strong predictor of the risk of MI in women, but not in men. These different results may be explained by the associations found between fat distribution and hypertension, impaired glucose tolerance and hypertriglyceridemia. IntroductionThe rapidly increasing global prevalence of overweight and obesity is a cause of great concern owing to the wide-ranging pathologic consequences of the condition. 1 Thus, considerable effort has been made to understand the pathogenic mechanisms of obesity. The relative contributions of total versus regional adiposity to metabolic and cardiovascular disease (CVD) risk have long been debated. 2 Although total adiposity is a risk factor for impaired glucose tolerance, type 2 diabetes and heart disease, 3,4 some obese individuals remain free from cardiovascular disease. 5,6 These observations suggest that adipose distribution, particularly around the viscera, may be the major risk factor for the aforementioned diseases, rather than adipose mass per se. Previous cross-sectional and prospective studies have reported the relationships between waist circumference and several CVD risk factor levels and end points. 16,18,19 However, very few prospective studies exist in which the relationships between objectively measured abdominal adipose mass and cardiovascular end points have been reported. 20,21A method that is rarely used in studies concerning regional fat mass is dual-energy X-ray absorptiometry (DEXA), although studies have shown it to be just as good or even better in respect to visceral fat mass than anthropometric measurements. 22 Furthermore, to our knowledge, no prospective studies have investigated the relationship between gynoid adipose mass and cardiovascular end points. The purpo...

This is an accepted version of a paper published in Osteoporosis International.Citation for the published paper: Wiklund, P., Nordström, A., Jansson, J., Weinehall, L., Nordström, P. (2012 Abstract SummaryThe association between bone mineral density (BMD) and myocardial infarction (MI) was investigated in 6872 men and women. For both men and women lower BMD in the femoral neck and hip was associated with increased risk of MI largely independent of smoking, hypertension, hypertriglyceridemia and diabetes.Purpose The relationship between bone mineral density (BMD) and cardiovascular disease isn't completely understood. The objective of this prospective study was to investigate the risk of myocardial infarction (MI) in relation to bone mineral density and to determine if cardiovascular risk factors could explain this association.Methods Dual X-ray absorptiometry (DEXA) was performed in 5490 women and 1382 men to determine total hip and femoral neck bone mineral density (BMD, g/cm²) and estimate femoral neck volumetric BMD (vBMD, g/cm³) . During a mean follow-up time of 5.7 years 117 women and 79 men suffered an initial MI. Conclusion Lower BMD was associated with an increase in MI risk for both men and women. Women had consistently lower HRs compared to men in all models. Adjusting for smoking, hypertension, hypertriglyceridemia and diabetes did not distinctively weaken these associations.