An echolucent carotid artery intima-media complex is a new and independent predictor of mortality in an elderly male cohort.

BACKGROUND: The echogenicity of atherosclerotic plaques is a measure of their lipid content and predicts cardiovascular disease. We hypothesized that the echogenicity of the non-plaque-affected arterial wall may be prognostically important as well, and more easily used as not all subjects carry plaques. We investigated the prognostic value of intima-media (IM) echogenicity (measured as the grey scale median [GSM]) for mortality compared with intima-media thickness (IMT) in a population-based sample of elderly men. METHODS: A cohort from a community-based sample of 491 men was investigated with carotid artery ultrasound at age 75. IMT and GSM for IM and plaques were measured in the far wall of the common carotid artery being apparently free of plaque. Cox proportional hazard analysis models were used to investigate linear and non-linear relations of IM-GSM to mortality, adjusted for IMT, body mass index, cholesterol, HDL-cholesterol, triglycerides, systolic blood pressure, antihypertensive treatment, CRP, diabetes, current smoking, pack years of smoking, and previous cardiovascular disease. RESULTS: Seventy-seven subjects died during a median follow-up time of 5.1 years. Participants were divided in tertiles by IM-GSM. In unadjusted analysis, IM-GSM predicted mortality in a U-shaped manner. In Cox proportional hazard analyses, an echolucent IM-GSM was a predictor of all-cause mortality (HR: 3.23; CI: 1.60-6.54; p<0.05) and CVD mortality (n=30, HR: 8.29; CI: 2.03-33.92; p<0.05) independently of IMT and established risk factors. These associations were still significant following adjustment for plaque occurrence and plaque echogenicity. CONCLUSION: An echolucent intima-media complex is a predictor of all-cause and CVD mortality in elderly men independently of plaque occurrence, plaque GSM, IMT and established risk factors, suggesting the echogenicity of the apparently plaque-free intima-media complex provides novel prognostic information regarding mortality after age 75.

Both cyclooxygenase- and cytokine-mediated inflammation are associated with carotid intima-media thickness.

BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is a valid index of atherosclerosis, which is viewed as an inflammatory disease. It is unknown if various modes of inflammation (cyclooxygenase [COX]-mediated, cytokine-mediated), oxidative stress and anti-oxidants are independently related to CCA-IMT. METHODS AND RESULTS: We investigated cross-sectional relations between CCA-IMT measured by B-mode ultrasound and COX-mediated inflammation (as measured by 15-keto-dihydro-prostaglandin F(2alpha) [PGF(2alpha)], cytokine-mediated inflammation (interleukin-6 [IL-6], high sensitivity C-reactive protein [hsCRP] and serum amyloid A protein [SAA]), oxidative stress (8-iso-PGF(2alpha), an F(2)-isoprostane; a non-enzymatic, free radical-induced product of arachidonic acid), and tocopherols (anti-oxidants) in a small subset of a population-based sample of elderly men (n=234) stating no use of anti-inflammatory medications. In a backward-stepwise regression analysis of correlates of CCA-IMT (with PGF(2alpha), hsCRP, IL-6, SAA, F(2)-isoprostanes, tocopherols, diabetes, body mass index (BMI), beta-blocker, statin treatment, smoking, hypertension and cholesterol), PGF(2alpha), CRP, beta-blocker treatment, diabetes and BMI were independently associated with CCA-IMT. There were no associations between F(2)-isoprostanes or tocopherols and CCA-IMT in this study. CONCLUSION: This study suggests both COX- and cytokine-mediated inflammation to be independently associated with increased CCA-IMT, implying that there might be more than one mode of inflammation involved in atherogenesis.

Apolipoprotein E epsilon4 genotype is independently associated with increased intima-media thickness in a recessive pattern.

Polymorphisms in the apolipoprotein E (Apo E) gene have been associated with lipid levels, carotid intima media thickness (CCA-IMT), inflammation and cardiovascular disease (CVD). Earlier findings suggested an association of the Apo E alleles with increased CCA-IMT following a recessive pattern. Whether associations might be independent of C-reactive protein (CRP), lipid levels and other CVD risk factors is not known. We investigated the relationships between Apo E (epsilon2, epsilon3 and epsilon4 alleles) and CCA-IMT, measured by B-mode ultrasound, in dominant and recessive models in a community-based sample of 437 men 75 years of age. In men homozygous for the epsilon4 allele CCA-IMT was significantly increased by 0.13 mm to 0.86 +/- 0.16 mm compared to 0.73 +/- 0.19 mm in non- epsilon4-carriers (P = 0.0012) and 0.73 +/- 0.21 mm in epsilon4 heterozygous (P = 0.0044) in unadjusted recessive models. The association between Apo E epsilon4 genotype and CCA-IMT was independent of Apo E epsilon2 and Apo E epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes) (P = 0.018). No relations between Apo E genotype and CCA-IMT were observed in dominant models. No significant associations between the Apo E epsilon2 and epsilon3 alleles and CCA-IMT were found. In this study, men homozygous with the ApoE epsilon4 allele had thicker CCA-IMT, independently of Apo E epsilon2 and epsilon3 alleles, CRP, lipid variables (TG, LDL, HDL) and other CVD risk factors (smoking, hypertension, body mass index, diabetes), suggesting CCA-IMT to be modified by the ApoE epsilon4 genotype in a recessive pattern.

Impaired insulin sensitivity is an independent predictor of common carotid intima-media thickness in a population sample of elderly men.

Most previous studies of associations between insulin sensitivity and common carotid artery (CCA) atherosclerosis have been conducted in small samples, have not used direct measurement of insulin sensitivity, and have yielded inconclusive results. We investigated associations of CCA intima-media thickness (IMT) and diameter (CCA-D) measured by B-mode ultrasound and insulin sensitivity measured by the euglycemic hyperinsulinemic clamp test together with risk factors of the insulin resistance syndrome in a community-based sample of 493 elderly men. The clamp glucose disposal rate was an independent predictor of CCA-IMT in multivariate models adjusting for blood pressure, smoking, serum cholesterol, and body mass index (1% decrease in CCA-IMT for a 1 unit increase in glucose disposal rate, P=0.009). Glucose disposal rate was significantly related to CCA-D in univariate (r=-0.11, P=0.02) but not in multivariate models. In conclusion, this study is the first to establish impaired insulin sensitivity, measured by the euglycemic hyperinsulinemic clamp test, as an independent predictor of CCA-IMT in a population-based sample of elderly men.