Novel epidemiologic and mechanistic aspects of the metabolic syndrome

Introduction: The metabolic syndrome is a cluster of cardiometabolic risk factors that increase risk of developing cardiovascular disease. Its prevalence continues to rise worldwide and it is becoming a public health burden. The aim of my thesis was to help elucidate some of the epidemiologic and mechanistic aspects behind the metabolic syndrome.

Material and Methods: For paper I the National Health and Nutrition Examination Survey (NHANES) III was used. For paper II the NHANES III Mortality study was used with follow-up mortality on NHANES III subjects. For paper III, the 60 year old Stockholm county cohort, the Swedish Diet and metabolic syndrome (KOMET) study and the NHANES 2005-06 cohorts were used. For paper IV, the 65 year old Stockholm County physical activity intervention study was used.

Results: Paper I showed that the apolipoproteinB/apolipoproteinAI (apoB/apoAI) ratio is strongly associated with insulin resistance beyond the association explained by traditional risk factors, metabolic syndrome components, and inflammatory risk factors. Paper II showed that apolipoprotein measurements significantly predict coronary heart disease (CHD) death, independently of cardiovascular (CV) risk factors and that this predicting ability was better than any of the routine clinical lipid measurements. Paper III showed that gamma glutamyl transferase (GGT) is significantly associated with the metabolic syndrome in elderly asymptomatic subjects and that this association seems to be mediated, at least in part by C-reactive protein (CRP). Paper IV showed that change in adipose tissue gene expression is associated with changes in metabolic syndrome parameters. Furthermore, lifestyle modification can influence changes in adipose tissue gene expression, which may in turn modulate metabolic syndrome parameters.

Conclusions: ApoB/apoAI ratio is a marker of insulin resistance. Apolipoprotein B should be included in guidelines assessing cardiometabolic risk. GGT relationship to the metabolic syndrome seems to be mediated, at least in part, by changes in CRP. Changes in parameters of the metabolic syndrome seem to be mediated, at least in part, by changes in adipose tissue gene expression after increased physical activity.

List of scientific papers

I. Sierra-Johnson J, Romero-Corral A, Somers VK, Lopez-Jimenez F, Walldius G, Hamsten A, Hellénius ML, Fisher RM (2007). "ApoB/apoA-I ratio: an independent predictor of insulin resistance in US non-diabetic subjects." Eur Heart J 28(21): 2637-43. Epub 2007 Sep 1
https://pubmed.ncbi.nlm.nih.gov/17766927

II. Sierra-Johnson J, Fisher RM, Romero-Corral A, Somers VK, Lopez-Jimenez F, Ohrvik J, Walldius G, Hellenius ML, Hamsten A (2009). "Concentration of apolipoprotein B is comparable with the apolipoprotein B/apolipoprotein A-I ratio and better than routine clinical lipid measurements in predicting coronary heart disease mortality: findings from a multi-ethnic US population." Eur Heart J 30(6): 710-7. Epub 2008 Aug 1
https://pubmed.ncbi.nlm.nih.gov/18676970

III. Sierra-Johnson J, Sjögren P, Hamsten A, Rosell M, Basu S, DeFaire U, Hellenius ML, Fisher RM (2009). "Association between increased gamma glutamyl transferase activity and features of the metabolic syndrome is partially mediated by CRP: implications for cardiometabolic prevention." (Manuscript)

IV. Sierra-Johnson J, Kallings LV, Kolak M, Halldin M, Hamsten A, DeFaire U, Hellenius ML, Fisher RM (2009). "Modulation of adipose tissue Gene expression in relation to changes in metabolic syndrome parameters after prescribing physical activity in a 6-month randomized controlled intervention study." (Manuscript)