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      Serum insulin levels are associated with vulnerable plaque components in the carotid artery: the Rotterdam Study

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          Abstract

          Background

          To investigate the association between fasting serum insulin and glucose levels with atherosclerotic plaque composition in the carotid artery. Impaired insulin and glucose levels are implicated in the etiology of cardiovascular disease; however, their influence on the formation and composition of atherosclerotic plaque remains unclear.

          Methods

          In 1740 participants (mean age 72.9 years, 46% women, 14.4% diabetes mellitus) from the population-based Rotterdam Study, we performed carotid MRI to evaluate the presence of calcification, lipid core, and intraplaque hemorrhage in carotid atherosclerosis. All participants also underwent blood sampling to obtain information on serum insulin and glucose levels. Using logistic regression models, we assessed the association of serum insulin and glucose levels (per s.d. and in tertiles) with the different plaque components, while adjusting for sex, age, intima-media thickness, and cardiovascular risk factors.

          Results

          Serum insulin levels were associated with the presence of intraplaque hemorrhage (adjusted odds ratio (OR): 1.42 (95% CI: 1.12–1.7)) We found no association with the presence of calcification or lipid core. Sensitivity analyses restricted to individuals without diabetes mellitus yielded similar results. No associations were found between serum glucose levels and any of the plaque components.

          Conclusions

          Serum insulin levels are associated with the presence of vulnerable components of carotid plaque, specifically with intraplaque hemorrhage. These findings suggest a complex role for serum insulin in the pathophysiology of carotid atherosclerosis and in plaque vulnerability.

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          Most cited references24

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          Hyperinsulinemia as an independent risk factor for ischemic heart disease.

          Prospective studies suggest that hyperinsulinemia may be an important risk factor for ischemic heart disease. However, it has not been determined whether plasma insulin levels are independently related to ischemic heart disease after adjustment for other risk factors, including plasma lipoprotein levels. In 1985 we collected blood samples from 2103 men from suburbs of Quebec City, Canada, who were 45 to 76 years of age and who did not have ischemic heart disease. A first ischemic event (angina pectoris, acute myocardial infarction or death from coronary heart disease) occurred in 114 men (case patients) between 1985 and 1990. Each case patient was matched for age, body-mass index, smoking habits, and alcohol consumption with a control selected from among the 1989 men who remained free of ischemic heart disease during follow-up. After excluding men with diabetes, we compared fasting plasma insulin and lipoprotein concentrations at base line in 91 case patients and 105 controls. Fasting insulin concentrations at base line were 18 percent higher in the case patients than in the controls (P<0.001). Logistic-regression analysis showed that the insulin concentration remained associated with ischemic heart disease (odds ratio for ischemic heart disease with each increase of 1 SD in the insulin concentration, 1.7; 95 percent confidence interval, 1.3 to 2.4) after adjustment for systolic blood pressure, use of medications, and family history of ischemic heart disease. Further adjustment by multivariate analysis for plasma triglyceride, apolipoprotein B, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol concentrations did not significantly diminish the association between the insulin concentration and the risk of ischemic heart disease (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). High fasting insulin concentrations appear to be an independent predictor of ischemic heart disease in men.
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            The Rotterdam Study: 2018 update on objectives, design and main results

            The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1500 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
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              Carotid plaque MRI and stroke risk: a systematic review and meta-analysis.

              MRI characterization of carotid plaque has been studied recently as a potential tool to predict stroke caused by carotid atherosclerosis. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap with subsequent ischemic events. We performed a comprehensive literature search evaluating the association of carotid plaque composition on MRI with ischemic outcomes. We included cohort studies examining intraplaque hemorrhage, lipid-rich necrotic core, or thinning/rupture of the fibrous cap with mean follow-up of ≥1 month and an outcome measure of ipsilateral stroke or transient ischemic attack. A meta-analysis using a random-effects model with assessment of study heterogeneity and publication bias was performed. Of the 3436 articles screened, 9 studies with a total of 779 subjects met eligibility for systematic review. The hazard ratios for intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap as predictors of subsequent stroke/transient ischemic attack were 4.59 (95% confidence interval, 2.91-7.24), 3.00 (95% confidence interval, 1.51-5.95), and 5.93 (95% confidence interval, 2.65-13.20), respectively. No statistically significant heterogeneity or publication bias was present in the 3 main meta-analyses performed. The presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI of carotid plaque is associated with increased risk of future stroke or transient ischemic attack in patients with carotid atherosclerotic disease. Dedicated MRI of plaque composition offers stroke risk information beyond measurement of luminal stenosis in carotid atherosclerotic disease.

                Author and article information

                Journal
                Eur J Endocrinol
                Eur. J. Endocrinol
                EJE
                European Journal of Endocrinology
                Bioscientifica Ltd (Bristol )
                0804-4643
                1479-683X
                March 2020
                20 January 2020
                : 182
                : 3
                : 343-350
                Affiliations
                [1 ]Departments of Epidemiology , Erasmus MC, Rotterdam, The Netherlands
                [2 ]Radiology and Nuclear Medicine , Erasmus MC, Rotterdam, The Netherlands
                [3 ]Department of Cardiovascular Sciences , Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, University of Leuven, Leuven, Belgium
                [4 ]Department of Clinical Epidemiology , Harvard TH Chan School of Public Health, Boston, Massachusetts, USA
                [5 ]Cardiovascular Research Institute Maastricht (CARIM) , Maastricht University, Maastricht, The Netherlands
                [6 ]Institute of Social and Preventive Medicine (ISPM) , University of Bern, Bern, Switzerland
                Author notes
                Correspondence should be addressed to D Bos; Email: d.bos@ 123456erasmusmc.nl
                Article
                EJE-19-0620
                10.1530/EJE-19-0620
                7087499
                31958313
                602b3756-ca72-471f-a220-13850e20d203
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 07 August 2019
                : 20 January 2020
                Categories
                Clinical Study

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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