Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults

Aims/hypothesis

We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men.

Methods

We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17–18 years in middle-aged men.

Results

We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r?=?0.84–0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score.

Conclusions

The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.     

Plasminogen activator inhitor-1 associates with cardiovascular risk factors in healthy young adults in the Cardiovascular Risk in Young Finns Study

AimsHypofibrinolysis displayed by elevated serum plasminogen activator inhibitor 1 (PAI-1) level has been associated with cardiovascular disease (CVD) and its risk factors such as obesity and insulin resistance. However, no studies have examined associations between PAI-1 and CVD risk factors in healthy subjects. We examined associations between serum PAI-1, ultrasound markers of atherosclerosis and CVD risk factors and whether PAI-1 improves prediction of atherosclerosis over known risk factors in a cohort of asymptomatic adults.MethodsWe analyzed PAI-1 and CVD risk factors and assessed carotid intima-media thickness (cIMT), distensibility (CDist) and the presence of a carotid atherosclerotic plaque and flow-mediated dilation (FMD) ultrasonographically for 2202 adults (993 men and 1,209 women, aged 30–45 years) participating in the ongoing longitudinal cohort study, The Cardiovascular Risk in Young Finns Study. High cIMT was defined as >90th percentile and/or carotid plaque and low CDist and low FMD as <20th percentile.ResultsIn bivariate analyses, PAI-1 correlated directly with cIMT and the risk factors: blood pressure, BMI, waist and hip circumference, alcohol use, total and LDL-cholesterol, triglycerides, glomerular filtration rate, high-sensitivity CRP and glucose (all P < 0.005). PAI-1 was higher in men and increased with age. Inverse correlation was observed with CDist, HDL-cholesterol and adiponectin in both sexes, with testosterone and sex hormone binding globulin in men and with creatinine and oral contraceptive use in women (P < 0.005). Independent direct associations were observed between PAI-1 and waist circumference, serum triglycerides, insulin, alcohol use and age and inverse with serum creatinine, HDL-cholesterol and adiponectin. PAI-1 did not improve estimation of high cIMT, low CDist and low FMD over conventional risk factors (P for difference in area under curve ≥ 0.37).ConclusionPAI-1 was independently associated with several known CVD risk factors, especially obesity markers, in both men and women. However, addition of PAI-1 to known risk factors did not improve cross-sectional prediction of high cIMT, low CDist and low FMD suggesting that PAI-1 is not a clinically important biomarker in early atherosclerosis.     

Temporomandibular Disorders,Occlusion, and Neck Pain in Subjects with Facial Pain: A Case-Control Study

The etiology of facial pain is multifactorial. Based on the results of a questionnaire included in the study of the 1966 Northern Finland Birth Cohort, performed in 1997–98, we found an association of facial pain with subjective symptoms of temporomandibular disorders (TMD), neck pain and with occlusal factors reported by 5,696 subjects. The aim of the present study was to examine these associations clinically. In the year 2000, a new inquiry was sent to the following subjects living in Oulu: 1. all subjects who had reported facial pain in the former questionnaire (n=162) (case group); and 2. to a randomly selected group of nonpain controls (n=200), group matched for gender. Those who reported willingness to participate were invited to a clinical examination. Finally, the total number of subjects was 104, including 52 (10 men, 42 women) cases and 52 (10 men, 42 women) controls. Anamnestic data were collected, and clinical stomatognathic and musculoskeletal examinations were performed, both the clinicians and the subjects being unaware of the case-control status. Anamnestically, stress was the most often reported provoking factor for facial pain. Facial pain associated significantly with reported TMD symptoms and allergies. Based on clinical findings, most of the cases were classified in the myogenous subgroup of TMD. The risk for facial pain was six-fold in subjects with clinically assessed TMD, defined as moderate (Dill) or severe (Dilll) by Helkimo's clinical dysfunction index, almost six-fold in subjects with protrusion interferences and approximately three-fold in subjects with clinically assessed tenderness of distinct fibromyalgia (FM) points in the neck. According to the adjusted logistic regression analyses, TMD had the strongest influence on facial pain, followed by protrusion interferences, anamnestically reported allergies and “other headaches”. The present study shows that as well as being connected with TMD, facial pain is associated with pain and muscle tenderness in the neck area.     

Carotid artery intima-media thickness and elasticity in relation to glucose tolerance

The association between diabetes and subclinical atherosclerosis is well established. The effect of non-diabetic glucose intolerance on early atherosclerosis is not as straightforward, and the data regarding sex-related differences in this matter are limited. Therefore, our aim was to investigate these associations in men and women separately. We studied 1,304 Finnish men and women over 45?years of age who participated in the Finnish Health 2000 Survey. Ultrasonically determined carotid artery intima-media thickness and elasticity were used as markers of early atherosclerosis. Glucose tolerance was categorized according to the American Diabetes Association criteria for diabetes mellitus. Age-adjusted means for carotid artery intima-media thickness and elasticity indices were significantly (P?<?0.05) associated with glucose tolerance status in both sexes. There was a trend of increasing early atherosclerosis with the worsening of glucose tolerance in men and women. These associations were weakened in both sexes after further adjustments for other cardiovascular risk factors. In women, but not in men, significant (P?<?0.05) associations between glucose tolerance status and carotid artery elasticity were seen even after these further adjustments. Diabetes and non-diabetic glucose intolerance are associated with increased early carotid atherosclerosis compared with normal glucose tolerance in both sexes. Our results suggest that women with glucose intolerance may be in greater risk than men.     

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis

AIM: To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC).METHODS: In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS: Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression.CONCLUSION: The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.