Atherosclerosis in middle-aged men. A prospective study with focus on factors related to the metabolic syndrome

Abstract

The metabolic syndrome (MetS) is a clustering of cardiovascular disease CVD) risk factors. Pro-spective studies have demonstrated that patients with MetS are about three times more likely to experience CVD events than those without MetS. Up to one third of the adult population seems to be affected worldwide. There is a need to better delineate MetS and to clarify possible underlying mechanisms. The aim was to study MetS and mechanisms related to atherosclerosis development examined by B-mode ultrasound. A population-based sample of healthy 58-year-old men (n=391) with varying degrees of obesity and insulin sensitivity was examined at baseline and after 3 years. At baseline smoking, but not snuff use, was associated with carotid and femoral intima-media thickness (IMT), the occurrence of plaques and increased CRP. Smoking was associated with hyperinsulinaemia, dyslipidaemia and high blood pressure, i.e. components of MetS. In the prospective study (n=342), we examined change in occurrence of MetS (WHO and NCEP criteria), association between MetS and change in carotid IMT, and if the annual increase in IMT was associated with the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio, or oxidized LDL (oxLDL) at baseline. Carotid IMT was larger both at baseline and after 3 years in men with MetS, according to either of the definitions, compared to those without factors of the syndrome. Men with MetS (WHO) at both examinations showed an increase in carotid artery IMT. Men with MetS (WHO) at baseline tended to have a larger annual increase in IMT, compared to those not fulfilling the criteria or having no risk factors. More than 10% of the men had MetS both at baseline and after 3 years. Several of the components of MetS deteriorated during follow-up. The apoB/apoA-I ratio was strongly associated with the components of MetS at baseline and two thirds of the subjects with MetS, irrespective of definition had high apoB/apoA-I ratios (>0.90), compared to one third of those without the syndrome. The IMT change was associated with apoB, total cholesterol, LDL , triglycerides, and inversely with HDL and LDL particle size at entry, and there was a strong co-linearity between these variables. The subjects with an apoB/apoA-I ratio above the first tertile (0.74) had a higher annual increase in IMT, compared to those below this level, after adjustment for blood pressure and smoking. The oxLDL at entry, measured by a monoclonal antibody (mAb-4E6), but not LDL, was associated with the number and size of plaques at follow-up, also after adjustment for plaque status at entry. OxLDL at entry was associated with change in carotid IMT and in a stepwise multiple regression analysis this association remained after adjustment for other CVD risk factors. In conclusion, smoking but not snuff use, was associated with ultrasound-assessed athero-sclerosis. The WHO, but not the NCEP definition of MetS was accompanied by carotid IMT increase. The apoB/apoA-I ratio was related to MetS and the increase in carotid IMT. OxLDL was associated with the development of atherosclerotic plaques and increase in carotid IMT