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Background: Growth hormone (GH) has been linked to cardiovascular disease but the exact mechanism of this association is still unclear. We here test if the fasting levels of GH are cross-sectionally associated with carotid intima media thickness (IMT) and whether treatment with fluvastatin affects the fasting level of GH., Methods: We examined the association between GH and IMT in 4425 individuals (aged 46-68 years) included in the baseline examination (1991-1994) of the Malmö Diet and Cancer cardiovascular cohort (MDC-CC). From that cohort we then studied 472 individuals (aged 50-70 years) who also participated (1994-1999) in the β-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS), a randomized, double blind, placebo-controlled, single-center clinical trial. Using multivariate linear regression models we related the change in GH-levels at 12 months compared with baseline to treatment with 40 mg fluvastatin once daily., Results: In MDC-CC fasting values of GH exhibited a positive cross-sectional relation to the IMT at the carotid bulb independent of traditional cardiovascular risk factors (p = 0.002). In a gender-stratified analysis the correlation were significant for males (p = 0.005), but not for females (p = 0.09). Treatment with fluvastatin was associated with a minor reduction in the fasting levels of hs-GH in males (p = 0.05) and a minor rise in the same levels among females (p = 0.05)., Conclusions: We here demonstrate that higher fasting levels of GH are associated with thicker IMT in the carotid bulb in males. Treatment with fluvastatin for 12 months only had a minor, and probably not clinically relevant, effect on the fasting levels of hs-GH.

Background: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events., Methods: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity., Results: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites., Conclusion: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

Objective: To evaluate the progression of carotid intima-media thickness (IMT) in the common carotid artery (CCA) and the bifurcation over a mean follow-up of 16 years in relation to cardiovascular risk factors., Methods: The study population included 3426 middle-aged Swedish men and women participating in the 1991-1994 (baseline) and the 2007-2012 (re-examination) investigation of the cardiovascular cohort of the Malmö Diet and Cancer Study (MDCS)., Results: There were differences in risk factor patterns in arterial segments in that diabetes and male sex were associated with the progression of IMT in the bifurcation, but not in the CCA, and high-density lipoprotein cholesterol (HDL) was associated with the progression of IMT in the CCA, but not in the bifurcation. Favourable changes in systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL) and HDL during follow-up decreased the IMT progression rate in the CCA. There was a cumulative relationship between traditional cardiovascular risk factors (i.e., regular smoking, LDL/HDL-ratio ≥ 3, hypertension) and IMT progression rates. The odds ratio (OR) of high IMT CCA progression rate (>75th percentile) was 1.0 (reference), 1.4 (95% CI: 1.1, 1.7), 1.7 (95% CI: 1.3, 2.2) and 2.1 (95% CI: 1.4, 3.1), respectively, for individuals with none, one, two, and three risk factors., Conclusion: There were differences in the associations between risk factors and progression rate in different arterial segments. Favourable changes in SBP and lipids during the follow-up period were associated with reduced IMT progression rates in the CCA., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objective: Carotid intima-media thickness (IMT) is a measure of arterial thickening and a risk predictor for myocardial infarction and stroke. It is unclear whether IMT also predicts atrial fibrillation (AF). We explored the association between IMT and incidence of first AF hospitalization in a population-based cohort., Methods: IMT was measured in 4846 subjects from the general population (aged 46-68 years, 60% women) without a history of AF, heart failure or myocardial infarction. The Swedish in-patient register was used for retrieval of AF cases. IMT was studied in relation to incidence of AF., Results: During a mean follow-up of 15.3 years, 353 subjects (181 men, 172 women, 4.8 per 1000 person-years) were hospitalized with a diagnosis of AF. After adjustment for cardiovascular risk factors, the hazard ratio (HR) for incidence of AF was 1.61 (95% confidence interval (CI): 1.14-2.27) for 4th vs. 1st quartile of IMT in the common carotid artery. This relationship was also independent of occurrence of carotid plaque. The results were similar for IMT in the bifurcation., Conclusion: Carotid IMT was independently associated with incidence of hospitalized AF in this study of middle-aged subjects from the general population. The results suggest that arterial thickening can predict future AF., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: The role of inflammation as part of the explanation of socioeconomic differences in carotid atherosclerosis has not been specifically investigated., Methods and Results: The associations between socioeconomic position (SEP), C-reactive protein (CRP), and preclinical carotid atherosclerosis were investigated in a general population sample of 3921 middle-aged Swedish men and women. Common carotid intima-media thickness (IMT) and presence of carotid plaque (focal IMT > 1.2 mm) were determined by B-mode ultrasound. The results showed that low SEP was associated with increased levels of CRP, independently of established risk factors. Furthermore, common carotid IMT increased with increasing CRP-levels. Presence of carotid plaque increased with increasing CRP-levels in men, but not in women. While the socioeconomic differences in carotid IMT were weak, there were associations between low educational level and carotid plaque prevalence with an age- and sex-adjusted odds ratio (OR) of 1.39 (95% CI: 1.21, 1.59). A similar association was seen for having a manual occupation, OR = 1.23 (95% CI: 1.07, 1.42). The age- and sex-adjusted absolute differences in carotid plaque prevalence were 9% with regard to educational level and 7% with regard to occupational status. Adjustment for CRP caused only a minor attenuation of the association between SEP and carotid atherosclerosis., Conclusions: The association between SEP and carotid atherosclerosis as measured by carotid IMT and carotid plaque could only to a minor extent be referred to differences in low grade inflammation as measured by CRP.

Objectives: To explore the effect of social characteristics of residential areas on carotid atherosclerosis prevalence., Methods and Results: The associations among area social characteristics and B-mode ultrasound determined carotid plaque-score (a semi-quantitative scale measuring the degree of atherosclerosis in the carotid bifurcation area) were cross-sectionally investigated in a general population sample of 4033 men and women. Area socioeconomic circumstances were described through a social deprivation index calculated from migration rate, percentage residents with foreign citizenship among those with foreign background, dependency on social welfare support, and employment rate. Living in socially deprived areas was associated with an increased carotid plaque-score in both men (P for trend = 0.004) and women (P for trend = 0.007). These associations were only slightly reduced after adjustment for individual level indicators with a decrease of the absolute mean difference in carotid plaque-score between worse-off and better-off areas of 9% for men and 13% for women, whereas adjustment for risk factors turned the trend non-significant in women, however, not in men., Conclusions: Those living in socially deprived areas in general had more extensive carotid atherosclerosis. However, in these areas there were a substantial number of individuals with low degrees of carotid atherosclerosis and vice versa. Thus, with regard to conceptual ideas of causal inference, the social characteristics of an area seem to be associated with the prevalence of carotid atherosclerosis. However, with regard to benefits of prevention, focusing on geographical areas would probably give a restricted benefit, where only some high-risk individuals would be reached.

Background: Carotid intima-media thickness (IMT) is increasingly used as a surrogate marker for atherosclerosis. Its use relies on its ability to predict future clinical cardiovascular end points. We performed a systematic review and meta-analysis of data to examine this association., Methods and Results: Using a prespecified search strategy, we identified 8 relevant studies and compared study design, measurement protocols, and reported data. We identified sources of heterogeneity between studies. The assumption of a linear relationship between IMT and risk was challenged by use of a graphical technique. To obtain a pooled estimate of the relative risk per IMT difference, we performed a meta-analysis based on random effects models. The age- and sex-adjusted overall estimates of the relative risk of myocardial infarction were 1.26 (95% CI, 1.21 to 1.30) per 1-standard deviation common carotid artery IMT difference and 1.15 (95% CI, 1.12 to 1.17) per 0.10-mm common carotid artery IMT difference. The age- and sex-adjusted relative risks of stroke were 1.32 (95% CI, 1.27 to 1.38) per 1-standard deviation common carotid artery IMT difference and 1.18 (95% CI, 1.16 to 1.21) per 0.10-mm common carotid artery IMT difference. Major sources of heterogeneity were age distribution, carotid segment definition, and IMT measurement protocol. The relationship between IMT and risk was nonlinear, but the linear models fitted relatively well for moderate to high IMT values., Conclusions: Carotid IMT is a strong predictor of future vascular events. The relative risk per IMT difference is slightly higher for the end point stroke than for myocardial infarction. In future IMT studies, ultrasound protocols should be aligned with published studies. Data for younger individuals are limited and more studies are required.

The associations between educational level, preclinical carotid atherosclerosis and incident coronary events (CE), were investigated in a general population sample of 5399 Swedish middle-aged men and women without history of cardiovascular disease (CVD) over a median follow-up of 8.7 years. Presence of carotid plaque (focal intima-media thickness (IMT) >1.2mm) was determined by B-mode ultrasound. In the age- and sex-adjusted model, there was an inverse relationship between educational level and risk of future CE (p for trend=0.002). To explore if there were education differences between groups with similar degrees of preclinical carotid atherosclerosis stratified analyses were made. Those with low educational level without carotid plaque showed a slightly increased hazard rate ratio (HRR), 1.14 (95% CI: 0.65, 1.97), compared to those with high educational level without carotid plaque (reference group). For those with high educational level with carotid plaque the HRR was 1.53 (95% CI: 0.92, 2.55). Having both low educational level and carotid plaque was associated with a HRR of 2.72 (95% CI: 1.72, 4.31). Individuals with plaque generally had more unfavourable cardiovascular risk factor levels, regardless of educational level. However, after risk factor adjustment those with both low education and carotid plaque still had a two-fold increased risk of CE. The results imply that differences in the prevalence of preclinical atherosclerosis seem important in explaining education differences in future coronary morbidity.

Background: In order to better understand the role of work environment in the earlier stages of the cardiovascular disease process, we wanted to investigate the influence of work-related psychosocial factors on preclinical atherosclerosis., Methods: Cross-sectional data was used to examine the association between psychological job demands, job decision latitude, and carotid atherosclerosis in 2658 vocationally-active Swedish men and women, ages 46-65, from the general population. Odds ratios of carotid plaque prevalence and carotid artery intima-media thickness (IMT), determined by B-mode ultrasound, were estimated across combinations of job demands and decision latitude., Results: Women in job situations with high demands and low decision latitude ('job strain') showed a high plaque prevalence odds (odds ratio [OR] = 1.68, 95% CI: 1.14, 2.48), and a thicker IMT in the carotid bifurcation area (mean difference: 0.15 mm, 95% CI: 0.07, 0.23) compared with women in job situations with low demands and high decision latitude ('relaxed'). Adjustment for covariates only slightly reduced the magnitude of these associations. No such associations were seen in men. However, women in job situations with high demands and high decision latitude ('active') also showed high odds for carotid plaque, and a thicker IMT in the carotid bifurcation, compared with women in 'relaxed' job situations. In men, those in 'active' job situations had a low carotid plaque prevalence odds, while IMT in the carotid bifurcation did not differ from those in 'relaxed' job situations. Results showed only weak associations with IMT in the common carotid artery (CCA) in both men and women., Conclusion: The specific hypothesis that high job demands interact synergistically with low decision latitude in the development of carotid atherosclerosis could not be supported in this study, neither in men nor in women. Instead a more complex pattern of interaction between job demands and decision latitude was shown.

Objective: Socioeconomic status (SES) in adulthood is known to be related to carotid atherosclerosis. However, few studies have tried to assess its association with SES from a life-course perspective., Methods and Results: We examined the relationship between SES in childhood and in adulthood and carotid atherosclerosis in a general population of Swedish men and women. Carotid stenosis was determined by B-mode ultrasound. Results showed that women whose fathers' occupations involved unskilled manual labor had higher odds of carotid stenosis than did women whose fathers' occupations involved high- or medium-level nonmanual labor, even after adjustment for adult occupational status and risk factors (odds ratio 1.8, 95% CI 1.1 to 2.8). No such association appeared in men. Furthermore, the impact of life-course SES on atherosclerosis was examined by using an additive measure of one's combined SES during childhood and adulthood. Among women, the odds of carotid stenosis increased with a rise in exposure to low SES during the life-course (P for trend <0.001). In men, no such trend was found., Conclusions: The results indicate that the total life-course exposure to low SES, with contributions from childhood and adulthood, seems to play a role in atherogenesis in women. Such a pattern of association could not be shown in men.

The associations among educational level, occupational status, and atherosclerosis were investigated during 1992-1994 in a general population sample of 4,176 Swedish men and women. Carotid artery intima-media thickness (IMT) and carotid stenosis were determined by B-mode ultrasound. Socioeconomic differences in mean carotid IMT and odds ratios for carotid stenosis prevalence were estimated. In women, the associations among educational level, occupational status, and IMT were weak. In men, there was no association between education and IMT, while low occupational status was associated with a thicker IMT. Women with low education had an increased odds of carotid stenosis compared with women with high education (odds ratio (OR) = 2.04, 95% confidence interval (CI): 1.53, 2.73), while this pattern was weaker among men. Women in manual occupations had an increased odds of carotid stenosis compared with women in high- or medium-level nonmanual occupations (OR = 1.75, 95% CI: 1.29, 2.36), which could not be seen among men. After adjustment for risk factors, the association between IMT and occupational status in men disappeared, while the associations among educational level, occupational status, and carotid stenosis in women persisted. The results imply that the atherosclerotic process is associated with socioeconomic status in both sexes, and they also indicate the possibility of sex differences in the mechanisms connecting socioeconomic status to atherosclerosis.

Abstract: Background:: The carotid intima-media thickness (IMT) has been associated with incidence of stroke. Whether this association is independent of carotid plaque is controversial. Methods and results:: The associations among B-mode ultrasound determined common carotid IMT, carotid plaque (focal IMT>1.2mm) and incident stroke, were investigated in 5163 Swedish middle-aged men and women over a median follow-up of 7 years. Age and sex-adjusted carotid IMT, and carotid plaque were significantly (p &#60;0.05) related to future stroke. Adjustment for cardiovascular risk factors generally reduced the hazard rate ratios, however more prominently so with regard to the carotid measure of plaque than with IMT. The associations between carotid IMT and stroke remained after adjustment for presence of carotid plaque, and graded associations between carotid IMT and stroke was found both among those with and without carotid plaque. Conclusions:: In this population-based study, common carotid IMT was associated with incidence of stroke. This relation was independent of presence of carotid plaque. [Copyright &y& Elsevier]