Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis: the Rotterdam Study

Inflammatory mediators and soluble cell adhesion molecules predict cardiovascular events. It is not clear whether they reflect the severity of underlying atherosclerotic disease. Within the Rotterdam Study, we investigated the associations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 with noninvasive measures of atherosclerosis. Levels of CRP were assessed in a random sample of 1317 participants, and levels of IL-6 and soluble cell adhesion molecules were assessed in a subsample of 714 participants. In multivariate analyses, logarithmically transformed CRP (regression coefficient [beta]=-0.023, 95% CI -0.033 to -0.012) and IL-6 (beta=-0.025, 95% CI -0.049 to -0.001) were inversely associated with the ankle-arm index. Only CRP was associated with carotid intima-media thickness (beta=0.018, 95% CI 0.010 to 0.027). Compared with the lowest tertile, the odds ratio for moderate to severe carotid plaques associated with levels of CRP in the highest tertile was 2.0 (95% CI 1.3 to 3.0). Soluble intercellular adhesion molecule-1 levels were strongly associated with carotid plaques (odds ratio 2.5, 95% CI 1.5 to 4.4 [highest versus lowest tertile]). Soluble vascular cell adhesion molecule-1 was not significantly associated with any of the measures of atherosclerosis. This study indicates that CRP is associated with the severity of atherosclerosis measured at various sites. Associations of the other markers with atherosclerosis were less consistent.     

Change in body mass index from adolescence to young adulthood and increased carotid intima-media thickness at 28 years of age: the Atherosclerosis Risk in Young Adults study

Obesity has become a major health problem in Western societies by increasing the risk of atherosclerosis and cardiovascular disease. Although data on tracking of body mass index (BMI) are available, little is known about the impact of weight change over time on the development of vascular damage. OBJECTIVE: To evaluate the relationship between adolescent BMI as well as change in BMI from adolescence into young adulthood and cardiovascular risk, as estimated by common carotid intima-media thickness (CIMT). DESIGN: Cohort study. SUBJECTS: A total of 750 healthy young adults, aged 27-30 y, who attended secondary school in Utrecht, the Netherlands. MEASUREMENTS: Data on adolescent weight, height, blood pressure and puberty stage were available from the original school health records of the Municipal Health Service. At young adulthood, a questionnaire on cardiovascular risk factors was completed and fasting blood sample was drawn and common CIMT was measured. RESULTS: One standard deviation (s.d.) increase in adolescent BMI was associated with 2.3 microm [95% confidence interval (CI): 1.3; 3.3] increase in mean common CIMT in young adults after adjustment for gender, adolescent age, adolescent blood pressure, puberty stage and lumen diameter. Further adjustment for adult cardiovascular risk factors did not change the relationship (linear regression coefficient=2.1 microm/s.d.; 95% CI: 1.0; 3.1). Adjustment for adult BMI attenuated the association (linear regression coefficient=0.9 microm/s.d.; 95% CI: -0.3; 2.2) as the majority of overweight and obese adolescents remained overweight or became obese young adults. Subjects who remained in the upper BMI distribution from adolescence into young adulthood had a significantly higher common CIMT compared to those who showed relative weight loss over time (mean difference 14.7 mum; P<0.001). These latter showed similar CIMT values as individuals with constant low BMI. CONCLUSION: Adolescent BMI predicts cardiovascular risk, as estimated by common CIMT in young adulthood. Individuals who experience the largest increase in BMI and those who remain overweight over time have the thickest common CIMT.     

No signs of subclinical atherosclerosis after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers

BackgroundBRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10–40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system.MethodsThis cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models.ResultsMean CIMT was 692.7 μm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (β=0.68 μm; 95% CI –4.02, 5.38) and PWV (β=44 mm/s; 95% CI –32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers.ConclusionsWe found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short.     

Variables of the insulin resistance syndrome are associated with reduced arterial distensibility in healthy non-diabetic middle-aged women

Aims/hypothesis. The insulin resistance syndrome is related to arterial stiffness in diabetic subjects. Whether the insulin resistance syndrome is also related to arterial stiffness in non-diabetic subjects is less clear. We studied the association between variables of the insulin resistance syndrome in relation to arterial distensibility in healthy middle-aged non-diabetic women. Methods. This study was done in 180 non-diabetic women, aged 43–55, selected from the general population. Arterial distensibility was assessed in the carotid artery. The associations were evaluated using linear regression analyses. Results. Strong associations were found between arterial distensibility and the variables of the insulin resistance syndrome: body mass index, waist-to-hip ratio, high-density-lipoprotein-cholesterol, triglycerides, glucose, insulin, apolipoprotein A1, plasminogen activator inhibitor-1-antigen and tissue-type plasminogen activator-antigen. After additional adjustment for mean arterial pressure, common carotid arterial distensibility remained associated with body mass index: β-coefficient (95 % confidence interval) per kg/m²: –0.24 (–0.42; –0.06); waist-to-hip ratio: –26.62 (–40.59; –12.65) per m/m; triglycerides: –1.42(–2.77; –0.08) per mmol/l; plasminogen activator inhibitor–1-antigen: –0.01 (–0.02; –0.00) per ng/ml and borderline significant associated with high-density-lipoprotein-cholesterol: 1.93 (–0.01; 3.87; p = 0.07) per mmol/l. Clustering of variables of the insulin resistance syndrome was strongly related to decreased arterial distensibility which remained after adjustment for mean arterial pressure. No association was found between arterial distensibility and variables that are not part of the insulin resistance syndrome: total cholesterol, LDL-cholesterol and apolipoprotein B. Conclusion/interpretation. The results of this study show that variables of the insulin resistance syndrome are associated with decreased arterial distensibility of the common carotid artery in healthy non-diabetic subjects. [Diabetologia (2000) 43: 665–672] Received: 17 November 1999 and in revised form: 24 January 2000     

Risk factors for vascular disease and dementia.

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.     

Insulin treatment and cardiovascular disease; friend or foe? A point of view

BACKGROUND: Several observational studies have shown that higher insulin levels are associated with an increased risk of cardiovascular disease. If higher endogenous insulin levels are causally related to cardiovascular disease, one might expect an increased risk of cardiovascular disease in patients treated with insulin, as this results in high circulating insulin levels. Such risk elevation might counteract the benefits of tight glucose control. Our objective was to explore the relationship between insulin therapy and cardiovascular disease in Type 1 and Type 2 diabetes mellitus using information from available literature. SUMMARY OF COMMENT: Several experimental studies in animals and humans support the presence of a harmful effect of insulin on the vascular endothelium. In prospective follow-up studies increased insulin dosage was associated with increased risks of cardiovascular disease, although confounding by indication could not be excluded. Randomized controlled trials in diabetic patients, comparing conventional with intensive glucose-lowering treatment, although showing a reduction in microvascular disease, showed no significant difference in the incidence of cardiovascular disease. The results with respect to exposure to insulin are, however, difficult to interpret due to insufficient information on exposure to insulin levels as well as confounding by glycaemic control and body mass index. In addition, these studies were not designed to address the question whether higher insulin use relates to increased cardiovascular risk. CONCLUSION: Published research provides conflicting evidence as to whether exposure to high levels of exogenous insulin in diabetes mellitus affects the risk of cardiovascular disease. The currently available studies have a number of serious methodological restraints that limit accurate interpretation and conclusions in this area.     

Alveolar soft part sarcoma of the pituitary gland with secondary involvement of the right cerebral ventricle

An alveolar soft part sarcoma localised in the pituitary gland extended into the suprasellar region. Three years after surgical removal there was a recurrency in the occipital horn of the right cerebral ventricle. This type of tumour predominantly occurs in the limbs and has never been reported in the pituitary region.     

Progressive multifocal leukoencephalopathy: immunofluorescent demonstration of simian virus 40 antigen in CSF cells and response to cytarabine therapy

We report an instance of progressive multifocal leukoencephalopathy in which cytarabine administration was successful as demonstrated by clinical course and follow-up computerized tomography studies. In this case, simian virus 40 (SV40) antigen was demonstrated in CSF cells by the indirect immunofluorescence technique.