Predictors of carotid plaque progression over a 4-year follow-up in the Reykjavik REFINE-study.

BACKGROUND AND AIMS: Carotid plaque is an arterial marker suggested as a surrogate end point for cardiovascular disease. The aim of this study was to examine the association of risk factors at visit 1 with plaque formation and progression of total plaque area (TPA) during follow-up. METHODS: We examined 1894 participants (50-69 years of age) in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. RESULTS: Among those with no plaque at baseline, plaque formation was associated with low density lipoprotein, sex, waist, former smoker and physical activity. Furthermore, both the Icelandic Heart Association (IHA) coronary heart disease (CHD) risk score and the atherosclerotic cardiovascular disease (ASCVD) risk score were highly associated with plaque formation in these individuals (p < 0.001) and a better cardiovascular health score was protective. In those with plaque present at baseline, metabolic syndrome was associated with increased risk, while older age and statin use were associated with reduced risk of new plaque formation. Statin use was the only factor associated with the relative TPA progression, where participants not on treatment had 5.7% (p=0.029) greater rate of progression compared with statin users. CONCLUSIONS: A number of conventional risk factors at visit 1 were individually associated with plaque formation, also when combined into CHD and ASCVD risk scores, but not with the relative progression in TPA. Medical intervention with statins can reduce the relative progression rate of TPA in the general population with low grade of atherosclerosis, supporting statin use to slow progression of atherosclerosis.

Prevalence and determinants of carotid plaque in the cross-sectional REFINE-Reykjavik study.

OBJECTIVE: Carotid plaque and intima-media thickness are non-invasive arterial markers that are used as surrogate end points for cardiovascular disease. The aim was to assess the prevalence and severity of carotid plaque, and examine its determinant risk factors and their association to the common carotid artery intima-media thickness (CCA-IMT) in a general population. METHODS: We examined 6524 participants aged 25-69 years in the population-based REFINE (Risk Evaluation For INfarct Estimates)-Reykjavik study. Plaques at the bifurcation and internal carotid arteries were evaluated. Mean CCA-IMT was measured in the near and far walls of the common carotid arteries. RESULTS: The prevalence of minimal, moderate and severe plaque was 35.0%, 8.9% and 1.1%, respectively, and the mean CCA-IMT was 0.73 (SD 0.14) mm. Age, sex, smoking and type 2 diabetes mellitus (T2DM) were the strongest risk factors associated with plaque, followed by systolic blood pressure, total cholesterol, body mass index and family history of myocardial infarct. Low educational level was also strongly and independently associated with plaque. CCA-IMT shared the same risk factors except for a non-significant association with T2DM and family history of myocardial infarction (MI). Participants with T2DM had greater plaque prevalence, 2-fold higher in those <50 years and 17-30% greater in age groups 50-54 to 60-64, and more significant plaques (moderate or severe) were the difference in prevalence was 24% in age group 50-54 and ≥60% in older age groups, compared with non-T2DM. CONCLUSIONS: Carotid plaque and CCA-IMT have mostly common determinants. However, T2DM and family history of MI were associated with plaque but not with CCA-IMT. Greater prevalence and more severe plaques in individuals with T2DM raise the concern that with increasing prevalence of T2DM we may expect an increase in atherosclerosis and its consequences.

Carotid atherosclerosis and cardiovascular health metrics in old subjects from the AGES-Reykjavik study.

BACKGROUND: Ideal cardiovascular (CV) health by simultaneous presence of 7 ideal health metrics (blood pressure, cholesterol, glucose, smoking, BMI, physical activity and diet) has been defined by the American Heart Association. In the current study we investigated the association of a CV health score (range 0-14), on the extent and progression of carotid atherosclerosis, assessed as carotid intima-media thickness (cIMT) and total plaque area (TPA) by ultrasound at 5 years interval. METHODS AND RESULTS: A total of 219 participants (age 75.6 ± 5.1) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were studied. Men with poor (low) CV health score had greater TPA than those with more optimal (high) score (61.5 (SD: 32.3), 44.4 (24.2) and 37.7 (23.2) mm(2) for those with CV health score ≤6, 7-9 and ≥10 respectively, p < 0.05). In linear analysis for men, log TPA was 0.088 mm(2) (SE: 0.040 p < 0.05) smaller for each additional point in the CV health score. CV health score was not associated with TPA in women, or cIMT in either sex. TPA increased in both sexes between visits. However, CV health score did not predict carotid atherosclerosis progression. CONCLUSIONS: CV health score is associated with TPA in older men but not in women. Men with poor CV health score at the baseline visit had more extensive carotid atherosclerosis than those with better CV health score, although it did not predict the progression of carotid atherosclerosis.

Characterisation and expression of the paired box protein 7 (Pax7) gene in polymorphic Arctic charr (Salvelinus alpinus).

Arctic charr (Salvelinus alpinus L.) from Lake Thingvallavatn, Iceland occur as four distinct morphs: large benthivorous (LB), dwarf benthivorous (DB), piscivorous (PI) and planktonivorous (PL). The morphs differ with respect to body size, head morphology, growth rate, and life history. The aim of this study was to investigate the paired box protein 7 (Pax7) gene as a candidate for such polymorphisms due to its importance in cranio-facial, skeletal muscle, and central nervous system development. No variation in coding and intronic sequences was found between morphs. We identified 10 alternate Pax7 isoforms with insertions/deletions: a four-residue (GNRT) deletion, a GEASS insertion truncated by the first serine residue (GEAS), and a thirteen-residue insertion (GQYA/TGPEYVYCGT). The latter insertion with a threonine (T) contains a putative casein kinase II (CK-2) phosphorylation site. Pax7 spatial expression patterns were identical in embryos of DB-, LB-, and PL-morphs, and were similar to those described for zebrafish Pax7c, but a difference in temporal expression for segmentation was observed between DB and LB morphs. At the end of segmentation, novel expression was observed in the mandibular region as two bilateral domains. The potential role of multiple alternative splicing of the Pax7 gene for the generation of different Arctic charr morphs is briefly discussed.