Low serum adiponectin levels in childhood and adolescence predict increased intima-media thickness in adulthood. The Cardiovascular Risk in Young Finns Study.

INTRODUCTION: Low adiponectin levels may predict the development of atherosclerosis. We examined the association of childhood adiponectin with preclinical carotid atherosclerosis that is defined as plaque and/or high (≥95th percentile) intima-media thickness (IMT) at the carotid bifurcation in adulthood. METHODS: The Cardiovascular Risk in Young Finns Study is a cohort study on cardiovascular risk factors. We used risk factor data from the baseline study (1980) and ultrasound findings from the follow-ups (2001 and 2007). The study population included 1708 participants, aged 3-18 years at baseline. RESULTS: In multivariate analysis, childhood adiponectin was inversely associated with preclinical carotid atherosclerosis: odds ratio 0.68, 95% confidence interval (CI) 0.53-0.86, p = .001, for 1-SD increase in childhood adiponectin after adjusting for childhood non-high-density lipoprotein cholesterol, body mass index, and blood pressure. When examining the incremental predictive ability, we observed that compared to an approach utilizing only conventional risk factors, the model additionally including adiponectin levels improved c-statistics area under curve from 0.733 (95% Cl 0.694-0.771) to 0.748 (95% Cl 0.710-0.786), p = .02. CONCLUSIONS: Childhood adiponectin levels improve the prediction of carotid atherosclerosis in adulthood over conventional risk factors. This supports the idea that low adiponectin levels may have a role in the development of preclinical atherosclerosis. Key messages Childhood adiponectin levels improve the prediction of increased carotid intima-media thickness in adulthood over conventional cardiovascular risk factors. These results suggest that adiponectin levels measured in childhood may have a role in the atherosclerotic process.

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

AIMS: Hypofibrinolysis 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. METHODS: We 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. RESULTS: In 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). CONCLUSION: PAI-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.

Associations between serum uric acid and markers of subclinical atherosclerosis in young adults. The cardiovascular risk in Young Finns study.

BACKGROUND AND METHODS: Serum uric acid (SUA) is a suggested biomarker for established coronary artery disease, but the role of SUA in early phases of atherosclerosis is controversial. The relations of SUA with vascular markers of subclinical atherosclerosis, including carotid artery intima-media thickness (cIMT), carotid plaque, carotid distensibility (Cdist) and brachial flow-mediated dilatation (FMD) were examined in 1985 young adults aged 30-45 years. In addition to ordinary regression, we used Mendelian randomization techniques to infer causal associations. RESULTS: In women, the independent multivariate correlates of SUA included BMI, creatinine, alcohol use, triglycerides, glucose and adiponectin (inverse association) (Model R(2) = 0.30). In men, the correlates were BMI, creatinine, triglycerides, C-reactive protein, alcohol use, total cholesterol and adiponectin (inverse) (Model R(2) = 0.33). BMI alone explained most of the variation of SUA levels both in women and men (Partial R(2) âˆ¼ 0.2). When SUA was modeled as an explanatory variable for vascular markers, it directly associated with cIMT and inversely with Cdist in age- and sex-adjusted analysis. After further adjustments for BMI or glomerular filtration rate, these relations were reduced to non-significance. No associations were found between SUA and FMD or the presence of a carotid plaque. Mendelian randomization analyses using known genetic variants for BMI and SUA confirmed that BMI is causally linked to SUA and that BMI is a significant confounder in the association between SUA and cIMT. CONCLUSION: SUA is associated with cardiovascular risk markers in young adults, especially BMI, but we found no evidence that SUA would have an independent role in the pathophysiology of early atherosclerosis.

Association of liver enzymes with metabolic syndrome and carotid atherosclerosis in young adults. The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: We examined whether metabolic syndrome (MetS) predicts increased alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) levels in young adults, whether spontaneous recovery from MetS has a favorable effect on liver enzyme activities, and whether these enzymes contribute to the atherogenicity of MetS (assessed by carotid intima-media thickness (IMT)). METHODS: The study included 1,553 subjects (base-line age 31.5 ± 5.0 years). ALT and GGT were measured in 2007. MetS was diagnosed by the new Joint Interim Societies definition. RESULTS: ALT and GGT levels were higher in subjects with MetS compared to those without in 2007. The association was independent of alcohol intake and BMI. In multivariable models adjusted for base-line age, LDL cholesterol, CRP, alcohol intake, and adiponectin, MetS in 2001 predicted increased ALT (ß ± SEM = 0.320 ± 0.062, P < 0.0001 in men; 0.134 ± 0.059, P = 0.02 in women) and GGT (ß ± SEM = 0.222 ± 0.067, P < 0.0001 in men; 0.236 ± 0.060, P < 0.0001 in women) levels after 6 years. Subjects with MetS only at base-line (2001) had lower ALT levels after 6 years compared to subjects with persistent and incident MetS. No statistically significant interaction for MetS*ALT (P = 0.81) or MetS*GGT (P = 0.92) on IMT was observed. CONCLUSION: In young adults MetS may induce liver enzyme changes that indicate increased risk of non-alcoholic fatty liver disease, but we found no evidence that increased enzyme levels would amplify the atherogenicity of MetS.

Cross-sectional associations between physical activity and selected coronary heart disease risk factors in young adults. The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Physical activity (PA) may reduce the risk of coronary heart disease (CHD) by inducing beneficial changes in several risk factors. We studied the associations between PA and a range of risk markers of CHD in young adults. METHODS AND RESULTS: We measured serum lipoproteins, oxidized LDL, adipokines, inflammatory markers, metabolic markers, and arginine metabolites in 2,268 individuals (age 24-39 y). Participants were asked frequency, duration, and intensity of PA in leisure time. In addition, commuting to work was assessed. In both sexes, PA was inversely associated with waist circumference (all P < 0.0001). After controlling for sex, age, and waist circumference, PA was directly associated with HDL-cholesterol and apolipoprotein A1, and inversely with heart rate, smoking, oxidized LDL, apolipoprotein B, insulin, glucose, C-reactive protein, leptin, L-arginine, and phospholipase A2 activity (all P < 0.05). CONCLUSION: These population-based data are consistent with the idea that the beneficial effects of PA on CHD risk are mediated by favorable influences on several risk factors, as judged by independent relations to markers of lipoprotein metabolism, glucose metabolism, and inflammation. These associations reflect beneficial effects on cardiovascular health in both sexes and may offer mechanistic insights for the inverse association between PA and CHD.

A longitudinal analysis on associations of adiponectin levels with metabolic syndrome and carotid artery intima-media thickness. The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Adipose-tissue derived adiponectin has gained a lot of interest as a marker of metabolic syndrome (MetS) and cardiovascular risk. The objective of this study was to assess whether adiponectin levels in young adults predict the incidence of MetS after 6-year follow-up. To gain insight on the interrelations between MetS, adiponectin and cardiovascular risk, we also examined the associations of adiponectin and carotid atherosclerosis according to MetS status. METHODS: This analysis was part of a population-based, longitudinal cohort study conducted among 1693 Cardiovascular Risk in Young Finns Study individuals (age 31.9 ± 4.9 years in 2001) participating in follow-ups in 2001 and 2007. RESULTS: In a multivariable model adjusted for age, sex, MetS components, LDL-cholesterol, CRP, insulin, leptin, smoking and family history of coronary disease, 1-unit increase in baseline adiponectin levels was associated with reduced odds (odds ratio [OR]=0.94, 95% CI 0.89-0.99, P=0.04) of incident MetS. Of the MetS components, adiponectin levels were inversely associated with the incidence of hyperglycemia in multivariable analyses (OR=0.94 (0.90-0.99), P=0.04). When studying the adiponectin×MetS interaction on IMT, we observed a significant interaction when examining IMT in 2001 (r=-0.11 (MetS(-)) vs. r=-0.17 (MetS(+)), P for interaction 0.047) and IMT in 2007 (r=-0.12 (MetS(-)) vs. r=-0.21 (MetS(+)), P for interaction 0.005), suggesting the inverse association between adiponectin and IMT is stronger among those with MetS. CONCLUSIONS: Among young adults, high adiponectin levels were associated with decreased incidence of MetS. Moreover, our data suggest that individuals with MetS are more vulnerable to the proatherogenic effects of low adiponectin levels.

Adiponectin is related with carotid artery intima-media thickness and brachial flow-mediated dilatation in young adults--the Cardiovascular Risk in Young Finns Study.

AIMS: Adiponectin may be involved in the pathogenesis of atherosclerosis. We investigated the relation of adiponectin on early functional and structural markers of subclinical atherosclerosis in a large population-based cohort of young men and women. METHODS AND RESULTS: We measured serum adiponectin using radioimmunoassay in 2,147 young adults (ages 24-39 years) participating in the Cardiovascular Risk in Young Finns Study. The subjects had ultrasound data on carotid intima-media thickness (IMT), carotid artery elasticity (n = 2,139) and brachial flow-mediated dilatation (FMD) (n = 1,996). In univariate analysis, adiponectin was inversely associated with IMT (r = -0.16, P < 0.0001) and directly with FMD (r = 0.12, P < 0.0001) and carotid elasticity (r = 0.20, P < 0.0001). The associations for IMT and FMD remained significant in multivariable models adjusted for age, sex, obesity indices, serum lipids, blood pressure, leptin, glucose, and C-reactive protein: IMT (ß = -0.018 ± 0.005, P = 0.0002) and FMD (ß = 0.72 ± 0.25, P = 0.004). The relation between adiponectin and carotid elasticity attenuated to non-significant after adjusting for waist circumference and systolic blood pressure. CONCLUSION: In young healthy adults, low serum adiponectin concentration is independently related with increased carotid IMT and attenuated brachial FMD, supporting the role of adiponectin in the pathogenesis of early atherosclerosis.

Non-alcoholic and alcoholic fatty liver disease - two diseases of affluence associated with the metabolic syndrome and type 2 diabetes: the FIN-D2D survey.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is known to be associated with the metabolic syndrome (MetS) and abnormal glucose tolerance. Whether alcoholic fatty liver disease (AFLD) is associated with similar metabolic abnormalities has not been examined in a population-based study. We aimed at assessing the prevalences of NAFLD and AFLD, and to examine to what extent these conditions are associated with MetS and abnormal glucose tolerance. METHODS: The cohort included 2766 Finnish subjects (45-74 years) from the population-based FIN-D2D survey. Features of insulin resistance, components of the MetS, glucose tolerance status by oral glucose tolerance test, serum liver enzyme concentrations, and daily alcohol consumption were assessed. RESULTS: Subjects with NAFLD and AFLD were equally obese and had similar fasting and insulin concentrations. The prevalences of NAFLD and AFLD were 21% (95% CI: 19%-22%) and 7% (95% CI: 6%-8%). The MetS was slightly more prevalent in AFLD (73%) than in NAFLD (70%, p = 0.028), and type 2 diabetes was similarly prevalent in NAFLD and AFLD (24-25%). The MetS and type 2 diabetes were more prevalent in subjects with NAFLD or AFLD compared to subjects with normal LFTs (53% and 14%, p < 0.0001 for both). DISCUSSION AND CONCLUSION: In Finnish middle-aged population, the prevalence of NAFLD is 3-fold higher than that of AFLD. The prevalences of MetS and type 2 diabetes are, however, significantly increased in both NAFLD and AFLD compared to subjects with normal LFTs. Subjects with AFLD are thus similarly metabolically unhealthy as subjects with NAFLD.

High prevalence of obesity, central obesity and abnormal glucose tolerance in the middle-aged Finnish population.

BACKGROUND: There is a worldwide increase in the prevalence of obesity and disturbances in glucose metabolism. The aim of this study was to assess the current prevalence of obesity, central obesity and abnormal glucose tolerance in Finnish population, and to investigate the associations between body mass index (BMI), waist circumference and abnormal glucose tolerance. METHODS: A cross-sectional population-based survey was conducted in Finland during October 2004 and January 2005. A total of 4500 randomly selected individuals aged 45-74 years were invited to a health examination that included an oral glucose tolerance test. The participation rate was 62% in men and 67% in women. RESULTS: The prevalence of obesity was 23.5% (95% Confidence Interval (CI) 21.1-25.9) in men, and 28.0% (95% CI 25.5-30.5) in women. The overall prevalence of abnormal glucose tolerance (including type 2 diabetes, impaired glucose tolerance, or impaired fasting glucose) was 42.0% (95% CI 39.2-44.8) in men and 33.4% (95% CI 30.9-36.0) in women. The prevalence of previously unknown, screen-detected type 2 diabetes was 9.3% (95% CI 7.7-11.0) in men and 7.3% (95% CI 5.9-8.7) in women. Central obesity was associated with abnormal glucose tolerance within each of the three BMI categories normal (< 25 kg/m2), overweight (25-29 kg/m2), and obese (>or= 30 kg/m2). CONCLUSION: In a population-based random sample of Finnish population, prevalences of obesity, central obesity and abnormal glucose tolerance were found to be high. A remarkably high number of previously undetected cases of type 2 diabetes was detected. Waist circumference is a predictor of abnormal glucose tolerance in all categories of obesity.

The association between obesity and the prevalence of low back pain in young adults: the Cardiovascular Risk in Young Finns Study.

Both low back pain (LBP) and obesity are common public health problems, yet their relation remains controversial. The aim of this study was to investigate the associations between weight-related factors and the prevalence of LBP in young adults in Finland. Participants in the ongoing Cardiovascular Risk in Young Finns Study aged 24-39 years were included (N = 2,575). In 2001, 31.2% of men and 39.5% of women reported LBP with recovery within a month or recurrent or continuous pain during the preceding 12 months. For women only, those with higher body mass index, waist circumference, hip circumference, waist-to-hip ratio, serum leptin level, and C-reactive protein level showed an increased prevalence of LBP. With all weight-related factors in the model, only waist circumference was related to LBP in women. For women, the odds ratios of LBP were 1.2 (95% confidence interval: 0.8, 1.8) for a waist circumference of 80-87.9 cm and 1.8 (95% confidence interval: 1.0, 3.2) for a waist circumference of > or =88 cm compared with a waist circumference of <80 cm. This association was independent of C-reactive protein, leptin, and adiponectin levels. The authors' findings in a relatively young population suggest that abdominal obesity may increase the risk of LBP in women.

Cross-sectional evaluation of the Finnish Diabetes Risk Score: a tool to identify undetected type 2 diabetes, abnormal glucose tolerance and metabolic syndrome.

The aim of this study was to assess the performance of the Finnish Diabetes Risk Score as a screening tool for undetected type 2 diabetes (T2D), abnormal glucose tolerance (AGT) and metabolic syndrome in the general population. In a cross-sectional, population-based survey, a total of 4,622 subjects aged 45-74 years were invited to a health examination that included an oral glucose tolerance test. Full data with risk score estimate and glucose tolerance status were available for 2,966 subjects without a prior history of diabetes. The risk score was associated with the presence of previously undiagnosed T2D, AGT, metabolic syndrome and cardiovascular risk factors. The area under the receiver operating curve for the prevalence of undiagnosed diabetes was 0.72 in men and 0.73 in women. The sensitivity using a cutoff risk score of 11 to identify undiagnosed diabetes was 66% in men and 70% in women; the corresponding false-positive rates were 31% and 39%, respectively. The area under the receiver operating curve for detecting the metabolic syndrome was 0.72 in men and 0.75 in women. The Finnish Diabetes Risk Score can be used as a self-administered test to screen subjects at high risk for T2D. It can also be used in the general population and clinical practice to identify undetected T2D, AGT and the metabolic syndrome.