Association of lifelong occupation and educational level with subclinical atherosclerosis in different European regions. Results from the IMPROVE study

Background and aims We aimed to examine the association between socioeconomic status (SES) and subclinical atherosclerosis, as assessed by carotid intima-media-thickness (C-IMT) and to investigate whether the effect of social inequality on C-IMT is mediated by cardiovascular (CV) risk factors and whether it is dissimilar in men and women, and in different European countries. Methods We assessed the association of lifelong occupation and educational level with C-IMT in the IMPROVE study cohort including 3703 subjects (median age 64.4 years; 48% men) from Southern (Italy), Western (France and the Netherlands) and Northern Europe (Finland and Sweden). Three summary measures of C-IMT (IMTmean, IMTmax, IMTmean-max), obtained from four segments of both carotids, were considered. Results After adjusting for conventional CV risk factors, current employment status and diet, C-IMT was higher in manual workers than in white collars (+7.7%, +5.3%, +4.6% for IMTmax, IMTmean-max and IMTmean, respectively; all p<.0001). Similar results were obtained by stratification for educational level. The effect of occupation on C-IMT was comparable in men and women and in different age groups, and was only partially mediated by differences in CV risk factors. Of note, the association of C-IMT with occupation was significant in Western and Northern Europe but not in Italy, with a significant statistical interaction (p = .0005). Conclusions Low SES was associated with subclinical atherosclerosis in subjects with at least three CV risk factors. Such association was stronger in Northern and Western Europe than in Italy. This difference was not completely explained by inequalities in CV risk factors and behavioural variables

A priori-defined Mediterranean-like dietary pattern predicts cardiovascular events better in north Europe than in Mediterranean countries

The Mediterranean Diet (MD) is a model of healthy eating contributing to a favorable health status, but its clinical usefulness is still debated. The aim of this study was to relate the adherence to MD with the incidence of cardio/cerebro-vascular events (VEs) in north and south European participants of the IMPROVE study

Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants

The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54–79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point &gt; zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06–1.47), CC-IMTmean (OR:1.22;1.04–1.44) and ICA-IMTmean (OR:1.26;1.07–1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis

Assessment and relevance of carotid intima-media thickness (C-IMT) in primary and secondary cardiovascular prevention

Interventions aimed to prevent cardiovascular diseases (CVD) are more effective if administered to subjects carefully selected according to their CVD risk. Usually, this risk is evaluated on the basis of the presence and severity of conventional vascular risk factors (VRFs); however, atherosclerosis, the main pathologic substrate of CVD, is not directly revealed by VRFs. The measurement of the arterial wall, using imaging techniques, has increased the early identification of individuals prone to develop atherosclerosis and to quantify its changes over time. B-mode ultrasound is a technique which allows a non-invasive assessment of the arterial wall of peripheral arteries (e.g. extracranial carotid arteries), and provides measures of the intima-media thickness complex (C-IMT) and additional data on the occurrence, localization and morphology of plaques. Being an independent predictor of vascular events, C-IMT has been considered as a tool to optimize the estimation of CVD risk but this application is still a matter of debate. Though the technique is innocuous, relatively inexpensive and repeatable, its use in the clinical practice is limited by the lack of standardized protocols and clear guidelines. This review outlines the rationale for the potential use of C-IMT in the stratification of cardio- and cerebro-vascular risk and discusses several topics related to the measurement of this variable, which are still controversial among experts of the field

Familial aggregation of carotid intima media thickness is better appreciable in young generational pairs

AIM: Carotid intima media thickness (C-IMT) aggregates at family level. It has been reported that the amount of offspring C-IMT variability explained by parents' C-IMT ranges from 20 to 92%. To assess whether this wide range of association is related to the age of generational pairs studied, we compared the amount of offspring C-IMT variability explained by parents\u2019 C-IMT detected in \u201cyoung generational pairs\u201d (offspring in paediatric age) with that of \u201cold generational pairs\u201d (parent in geriatric age). METHODS: We studied 201 individuals from 67 families, each consisting of a grandchildren, a parent and a grandparent. Each of them had C-IMTmean and C-IMTmax measured. The amount of offspring C-IMT variability explained by C-IMT of parents was expressed in terms of squared correlation coefficients (r2). The r2 of young and old generational pairs were then compared. RESULTS: The mean age (\ub1SD) of grandparents, parents and children was 70\ub18.3, 44\ub19.1 and 14\ub18.7, respectively. The corresponding figures for C-IMTmean was 1.17\ub10.19 mm, 1.11\ub10.35 mm and 1.06\ub10.28 mm, respectively. C-IMT variables of parents correlated with C-IMT of their offspring just in the young generational pairs (C-IMTmean: r2=0.34 p<0.0001; C-IMTmax: r2=0.21, p=0.001) but not in the old generational pairs. Analogous results were obtained when the analyses were repeated in groups homogeneous for gender (father Vs. son, mother Vs. daughter, etc). CONCLUSIONS: Familial aggregation of C-IMT is appreciable only in young generational pairs. This might be due to the fact that in older generational pairs, familial aggregation is masked by a higher prevalence of environmental confounders

Light or regular cigarette smoking: effect on brachial artery flow mediated dilation

AIM: Many smokers use light cigarettes in the belief that this may reduce the risk for health. In this study we investigated whether the effect of cigarette smoking on brachial artery flow mediated dilation (FMD%) is related to the cigarettes\u2019 content of tar, nicotine or carbon-monoxide. METHODS: 206 subjects (59% men, age 52\ub113 yr) participated in the study. FMD% was measured by B-mode ultrasound. Smoking habits were recorded on the basis of a face-to-face interview. Cigarettes\u2019 were defined as \u201clight\u201d or \u201cregular\u201d on the basis of a content of tar, nicotine and carbon monoxide above or below their respective medians. The chronic effect was assessed in 53 consumers of light cigarettes, 85 consumers of regular cigarettes and 68 never smokers. The acute effect was assessed in 51 and 29 smokers, who smoked a single light or regular cigarette smokers, respectively. In these subjects, FMD% was measured before and 10 min after smoking. RESULTS: FMD% of both light (5.66\ub13.18%) and regular cigarettes (6.15\ub13.33%) consumers were lower than that of never smokers (8.86\ub13.41%, p0.05). Both types of cigarettes induced an acute reduction of FMD% (Both p0.05). CONCLUSIONS: Consumption of light cigarettes does not reduce the detrimental effect of smoking on FMD% observed in consumers of regular cigarettes

L-arginine does not improve endothelial function in patients with metabolic syndrome

AIM: Metabolic syndrome (MS) is associated with impaired endothelial function. In this study we investigated whether L-Arginine improves endothelial dysfunction in patients with MS. METHODS: In a randomized double blind study, 38 subjects with MS received either 6.64 g/die of L-Arginine (n=19, group A) or placebo (n=19, group B) for 6 weeks. Flow mediated dilatation (FMD), systolic and diastolic blood pressure, visceral obesity, lipids, blood glucose, insuline, L-arginine, total NOx and symmetric and asymmetric dimethylarginine (SDMA and ADMA) were measured at baseline (T0) and at the end of the study (T6). RESULTS: At baseline, groups A and B differed just for waist circumference (100\ub17 vs. 107\ub112 cm; p<0.05). After treatment, beside the expected increases in both L-arginine (from 83\ub117 to 97\ub126 \ub5M; p=0.002) and of L-arginine/ADMA ratio (from 215\ub140 to 243\ub153; p=0.002) no change was detected in L-arginine treated group. An increase of total cholesterol (from 173\ub147 to 184\ub144 mg/dL, p=0.027), LDL (from 95\ub126 to 109\ub134 mg/dL, p=0.012), HDL (from 44\ub17 to 46\ub18 mg/dL, p=0.003) and ADMA (from 0.39\ub10.07 to 0.42\ub10.09 \ub5M, p=0.005) was observed in the placebo group. After data adjustment for possible confounders (age, pack-years and change in ADMA, arginine, blood glucose and pharmacological treatments) FMD significantly increased in the L-arginine treated group but not in the placebo group. Group A difference in FMD, however, lost its statistical significance after adjustment of the analysis for Brachial artery diameter measured at rest. CONCLUSIONS: The oral supply of L-Arginine does not influence the endothelial function in patients with MS

Potentially Spurious Correlations Between Arterial Size, Flow-Mediated Dilation, and Shear Rate

The use of indices formed from the ratio of 2 variables often generates spurious correlations with other variables that are mathematically coupled. In this context, we examined the correlations between percent flow-mediated dilation, baseline diameter, and shear rate. In a sample of 315 participants, with and without substantial vascular risk factors, the observed correlation coefficients between the variables were of a similar magnitude to those reported in the literature. We then applied a Monte Carlo procedure based on random permutations to remove any physical or physiological explanation for these correlations. We found that the median residual correlation coefficients were comparable with those observed in our original sample. When the confounding influence of artery size was adjusted for, the mean difference in percent flow-mediated dilation between high-risk and low-risk samples was halved. These findings indicate that the widely reported correlations between flow-mediated dilation, basal artery diameter, and shear rate have a substantial spurious component. This is because percent flow-mediated dilation and shear rate are mathematically coupled to artery size

The effects of tobacco smoke and of the social class on carotid intima media thickness (c-IMT) and on c-IMT progression are stronger in women than in men

Background: The harmful effect of smoking on atherosclerosis and cardiovascular health is well established. Educational campaigns have been successful in reducing the number of smokers in men but not in women, where the number of smokers (initially lower than men) is even increasing. Aim of the study: To investigate the gender differences in the association of tobacco smoke with subclinical atherosclerosis and atherosclerosis progression also taking into account the effects of other variables strongly associated with tobacco smoke: C reactive protein (CRP) and number of white blood cells (WBC) as inflammation markers, and education as an index of social class. Methods: The IMPROVE Study cohort includes 1694 men and 1893 women (age 54-79 yr) at high risk of cardiovascular disease of five European countries. Baseline mean and maximum IMT of the left and right common carotids, bifurcations and internal carotid arteries and the fastest IMT-progression (15 months of follow up) detected in the whole carotid tree regardless of its location were computed. Associations were assessed by multivariable analysis adjusting for conventional cardiovascular risk factors and recruiting centre. Results: Pack-years, a lifelong index of tobacco exposure, significantly associated with baseline C-IMT in both genders. However, the estimated C-IMT increase for each pack-year was more than double in women than in men (3.7\ub10.7 vs. 1.5\ub10.5 \ub5m) with a significant gender 7 dose interaction (P=0.01). Moreover, the estimated increase in the fastest C-IMT progression associated with a unit of cigarettes/day, an index of daily dose of tobacco exposure, was more than five-fold in women than in men (5.5\ub11.3 vs. 1.0\ub11.3 \ub5m/yr), (P-int =0.008). Also the relationships between C-IMT and CRP (P-int =0.015), WBC (P-int =0.011) and education (P-int =0.014) were different in men and women. Gender differences were also observed considering the relationships between current smoking and CRP (P-int =0.045) and WBC (P-int =0.049). Finally, a significant gender difference was also found in the relationship between education and smoking exposure (P-int =0.0003). Conclusions. The effects of tobacco smoking on cross-sectional subclinical atherosclerotic burden, and on carotid atherosclerosis progression appear to be more harmful in women than in men, prompting studies on gender specific mechanisms and development of preventive actions expressly oriented to women. Inflammation and social class seems to be implicated in the complex interrelation between tobacco smoke, gender and subclinical atherosclerosis

Familial aggregation of carotid artery intima media thickness: a three-generation study

BACKGROUND: Family history of premature cardiovascular events (FHPCE) is an independent risk factor for atherosclerosis and for vascular events, partially explainable by genetic or environmental atherosclerosis risk factors. Carotid intima media thickness (IMT) is a widely accepted subclinical marker of carotid and coronary atherosclerosis. On this basis, some authors have tried to confirm the nature of FHPCE as a risk factor for atherosclerosis by evaluating the amount of \u201coffspring-carotid IMT variability\u201d explained by parent\u2019s IMT. These studies, however, reported contrasting results with an amount of offspring IMT variability explained by parent\u2019s IMT ranging from 20 to 92%.(Moskau S et al., Stroke 2005;36;5-8) We hypothesized that these discrepancies might be related to the age of generational pairs (parent \u2013 offspring) studied. The contribution of parent\u2019s-IMT to offspring-IMT variability in relatively young generational pairs (for example when parent-age is lower than 60) might, in fact, be different from the one evaluated in generational pairs relatively older (for example parent-age>75) in which environmental factors might have had the time to act as confounders. METHODS: Sixty-seven grandchildren (33 men and 34 women), one of their parents (37 men and 30 women) and one of their grandparents (18 men and 49 women), were recruited. Each of them had their CC-IMTmean, Bif-IMTmean, ICA-IMTmean and IMTmean measured by B-Mode ultrasound. Simple linear regression analysis was used to investigate correlations between carotid IMT in the young generational pairs (grandchildren vs parents) as well as in the old generational pairs (parents vs grandparents). For each generational pairs, the squared correlation coefficient (r2) was used to evaluate the extent of offspring\u2019s carotid IMT variability explained by the carotid IMT of their respective parents. RESULTS: The mean age (\ub1SD) of grandparents, parents and children was 70\ub18.3, 44\ub19.1 and 14\ub18.7, respectively. The corresponding figures for IMTmean was 1.17\ub10.19 mm, 1.11\ub10.35 mm and 1.06\ub10.28 mm, respectively. Mean carotid IMT variables of progenitors correlated with carotid IMT of their offspring in the young generational pairs (IMTmean: r2 =0.34 p<0.0001; IMTmax: r2 =0.21, p=0.001) but not in the old generational pairs. CONCLUSIONS: Familial aggregation of carotid IMT is better appreciable in the young generational pairs. This may be due to the higher prevalence of potential confounding environmental factors in the older generational pairs