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Background: We studied the association between participation in the longitudinal follow-up study and cardiometabolic disorders in two longitudinal studies which started prospectively in the antenatal period: the Northern Finland Cohort 1966 (NFBC1966) and the Northern Finland Birth Cohort 1986 (NFBC1986). Both birth cohorts have been followed up since birth with multiple follow-ups including questionnaires, and clinical examinations., Methods: The NFBC studies were compared to comparison cohorts of individuals who were born in the same area as the study cohorts, but in different years. The data for the comparison cohort were obtained from registers. The cumulative incidence rates of hospital-treated cardiometabolic disorders were calculated for study and comparison cohorts covering the age of 7-50 years in NFBC1966 and the age of 0-29 years in NFBC1986. Cardiometabolic-related causes of death were analysed in NFBC1966 and the comparison cohort from the age of 0-50 years. The analysed cardiometabolic disorders were diabetes mellitus, coronary artery disease, hyperlipidaemia, obesity, hypertension, and cerebrovascular disorders. The risk ratio (RR) with 95% confidence intervals (CI) was calculated by sex., Results: In NFBC1966, no differences in cumulative incidences of cardiometabolic disorders or cardiometabolic-related deaths compared to the comparison cohort were found. Male members of NFBC1986 had decreased risk of obesity (RR: 0.45, 95% CI: 0.27-0.75) and any cardiometabolic disorders (RR: 0.75, 95% CI: 0.59-0.95) compared to the comparison cohort., Conclusions: The results suggest that participation in the NFBC1986 may have a weak positive health effect among men. Agreement to follow-up studies focusing on diet, substance use, and physical activity, may slightly decrease the incident risk of cardiometabolic disorders in the study population.KEY MESSAGESEven mild interventions, such as follow-up studies in the prospective follow-up studies, might affect participants' behaviour and consequently the incidence of cardiometabolic disordersThe fact that follow-up itself might affect the study population in terms of risk factors, has to be taken into account when estimating the representativeness of the followed population.

Background: Obesity and metabolic syndrome (MetS) are known to expose to atrial fibrillation (AF), cardiovascular diseases (CVD) and mortality. Metabolically healthy obesity refers to obesity without MetS. This study aimed to investigate how obesity and MetS modify the risk of CVD, AF and mortality in very long-time follow-up., Methods: Finnish middle-aged subjects ( n  = 1045) were grouped into four subgroups according to the presence of obesity and MetS. CVD events and AF were followed for 24 years and total mortality for 30 years. Moreover, 600 available patients had a follow-up visit for metabolic examinations after approximately 22 years., Results: One-hundred and sixty-two (30%) subjects without obesity or MetS died during the follow-up. Ninety-two (17%) of the patients in this group had a CVD event and 58 (11%) were diagnosed with AF. As compared to them, obese subjects without MetS had similar metabolic fate and mortality (mortality 26 (38%), p  = .143; CVD event 12 (18%), p  = .858 and AF 7 (10%), p  = .912, respectively), whereas subjects with obesity and MetS had greater mortality (102 (49%), p  < .001), more CVD (71 (34%), p  < .001) and AF (49 (23%), p  < .001). Non-obese individuals with MetS had greater rates of mortality (96 (44%), p  < .001) and CVD (80 (37%), p  < .001), but not of AF (26 (12%), p  = .606). Of the 40 subjects with obesity but without MetS at baseline and available for the follow-up visit, 15 (38%) were metabolically healthy at the follow-up visit., Conclusions: In the present long-term follow-up study, the presence of MetS, but not obesity only, implies a greater risk of mortality and CVD. The risk of AF is increased only in subjects with both obesity and MetS. However, obesity without MetS tends to progress eventually to obesity with MetS. Key messagesThe presence of metabolic syndrome (MetS), but not obesity only, entails a greater risk of mortality and cardiovascular diseases.The risk of atrial fibrillation is increased only in subjects with both obesity and MetS.Obesity without MetS tends to progress eventually to obesity with MetS.

Background: To estimate the ability of fasting, 1-h, and 2-h post-load glucose to predict cardiovascular outcomes., Methods: We examined a population-based study consisting of 977 middle-aged subjects who underwent an oral glucose tolerance test with glucose values measured at 0, 60, and 120 min. Participants were followed up to 24 years, and cardiovascular outcomes were collected from national registers. Predictive abilities of fasting, 1-h, and 2-h glucose were evaluated alone and in the prediction models with traditional cardiovascular risk factors using Cox proportional hazard models, the likelihood-ratio test, Harrell's concordance index and integrated discrimination improvement., Results: Cardiovascular endpoint occurred in 222 (22.7%) participants during a median follow-up of 19.8 years. In the prognostic models, 1-h glucose (HR 1.67, 95%CI 1.10-2.53), but not fasting or 2-h glucose, predicted cardiovascular events statistically significantly. In addition, when adding glucose parameters into the model including traditional cardiovascular risk factors, only 1-h glucose improved the predictive ability (LR-test p =.046). Finally, 1-h glucose found slightly over 50% more cardiovascular endpoints that were not recognized by fasting or 2-h glucose levels., Conclusions: Our findings support the earlier ones suggesting that 1-h glucose would be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h glucose.KEY MESSAGESIn addition to conventional CV risk factors,1-h but not fasting or 2-h post-load glucoses seems to be an independent predictor of cardiovascular events and seems to improve the predictive ability of the traditional cardiovascular risk model.Elevated 1-hpost-load glucose finds a large number (slightly over 50%)of cardiovascular endpoints that were not recognized by fasting or 2-h post-load glucose levels.One-hour glucose seems to be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h post-load glucose.

Aims: To evaluate risk factors for major adverse cardiac event (MACE) after the first acute coronary syndrome (ACS) and to examine the prevalence of risk factors in post-ACS patients., Methods: We used Finnish population-based myocardial infarction register, FINAMI, data from years 1993-2011 to identify survivors of first ACS ( n  = 12686), who were then followed up for recurrent events and all-cause mortality for three years. Finnish FINRISK risk factor surveys were used to determine the prevalence of risk factors (smoking, hyperlipidaemia, diabetes and blood pressure) in post-ACS patients ( n  = 199)., Results: Of the first ACS survivors, 48.4% had MACE within three years of their primary event, 17.0% were fatal. Diabetes (p = 4.4 × 10 -7 ), heart failure (HF) during the first ACS attack hospitalization (p = 6.8 × 10 -15 ), higher Charlson index (p = 1.56 × 10 -19 ) and older age ( p  = .026) were associated with elevated risk for MACE in the three-year follow-up, and revascularization ( p  = .0036) was associated with reduced risk. Risk factor analyses showed that 23% of ACS survivors continued smoking and cholesterol levels were still high (>5mmol/l) in 24% although 86% of the patients were taking lipid lowering medication., Conclusion: Diabetes, higher Charlson index and HF are the most important risk factors of MACE after the first ACS. Cardiovascular risk factor levels were still high among survivors of first ACS.

Background: Prediabetes has proven to have many unfavourable impacts on the cardiovascular system. Methods: The OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study included 1045 middle-aged subjects followed from the years 1990-1993 to 2014. The focus was on peptide hormones. Results: Plasma resistin levels were higher among prediabetics ( p  = .001), particularly impaired glucose tolerance (IGT) ( p  < .001), but not impaired fasting glucose (IFG) patients than among normal glucose tolerance (NGT) or diabetes groups. Diabetics showed lower resistin levels than IGT subjects ( p  < .001). IGT or diabetes groups showed lower adiponectin and higher leptin levels compared to the NGT group ( p  < .001). The IFG group had the highest blood pressure and left ventricular mass index, even higher than the diabetic group. Diabetics had the highest, prediabetics (IFG + IGT) intermediate and NGT the lowest risk for CVD events during follow-up ( p  < .001). Among prediabetics, high plasma ghrelin was an independent predictor of CVD events ( p  < .05) in the Cox regression analysis although it did not significantly improve either classification or discrimination of the patients. Conclusions: Among glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics. Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.KEY MESSAGEAmong glucose tolerance groups, patients with IGT had the highest resistin, but equally high leptin and low adiponectin levels as diabetics.Among prediabetics, ghrelin seems to predict independently cardiovascular events in the long term.

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes an enormous burden to human health and health-care systems all over the world. A great proportion of this burden results from increased risk of cardiovascular diseases. Atrial fibrillation (AF) is the most common chronic heart arrhythmia globally and it increases the risk of embolic stroke and heart failure. Recent studies have explored the association between NAFLD and AF with somewhat conflicting results. However, ultrasound-verified prospective studies concur that NAFLD is associated with the incidence of AF. According to epidemiological evidence, the greater the prevalence of NALFD in a population, the stronger the association with AF incidence and prevalence. Specifically, diabetic individuals with NAFLD are at the greatest risk of AF. Additionally, the risk of AF may concentrate most in individuals with advanced NAFLD, particularly those with liver fibrosis. The possible mechanistic factors between NAFLD and AF, particularly obesity and systemic inflammation, are diverse and form a complex interplaying network. However, further studies are needed to elucidate whether NAFLD has a causative role in the development of AF. The purpose of this article is to review and discuss the epidemiologic evidence and possible mechanistic links between these two conditions. KEY MESSAGES Although epidemiologic studies have provided conflicting results on the association of NAFLD and AF, prospective studies with ultrasound-verified NAFLD concur that NAFLD is associated with about 2-fold greater incidence of AF among general population and about 6-fold greater incidence among subjects with type 2 diabetes. The risk of AF among individuals with NAFLD is increased by other cardiovascular risk factors, especially type 2 diabetes and advanced age. The possible mechanistic links between NALFD and AF are diverse, with obesity and systemic inflammation having a significant role, but further studies are needed until NAFLD can be established as a causal factor in the incidence of AF.

Aim: To examine trends in incidence and 28-day case fatality of myocardial infarction (MI) in persons aged 75-99 years in four areas of Finland., Methods and Results: The Finnish Acute Myocardial Infarction (FINAMI) register is a population-based MI register study, which during 1995-2012 recorded 30561 suspected acute coronary syndromes in persons aged ≥75 years. Of them, 16229 fulfilled the American Heart Association criteria for a definite, probable or possible MI or coronary death. This age-group contributed 56.8% of all MIs of which 62.7% occurred in women. The incidence of MI decreased by -3.3%/year (95% CI -4.2; -2.4) in women aged 75-84 years, and by -1.2%/year (-1.9; -0.5) in women aged 85-99 years, but among men in these age-groups, only a non-significant reduction occurred. The 28-day case fatality of MI was high. In the age-group 75-84 years, it decreased non-significantly by -1.6%/year in men, and significantly by -2.4%/year (-3.9; -0.8) in women. In the age-group 85-99 years, the decrease was more remarkable: -5.1%/year (-7.8; -2.3) and -3.9%/year (-5.5; -2.2), respectively., Conclusions: In Finland, more than half of MIs occur in the age-group 75-99 years, and most of them in women. The incidence of MI decreased significantly in elderly women but non-significantly in elderly men. The 28-day case fatality decreased especially in the age-group 85-99 years. Key Messages In Finland, more than one half of all myocardial infarctions (MIs) occur in the age-group of 75 years or older. Furthermore, 62.7% of MIs among elderly patients occur among women, although 58.0% of the elderly population are women. The incidence of MI decreased significantly in elderly women but not in elderly men. The 28-day case fatality in elderly patients was high but decreased significantly during the study period 1995-2012. This study provides population-based data on treatment strategies and trends in incidence, event rate, mortality and case fatality of MI in elderly individuals. Elderly patients with acute coronary syndromes still present a remarkable burden to the healthcare system in Finland as well as in many other developed countries. Especially considering the modern trend of reducing hospital resources and shifting patient care to outpatient clinics, the epidemiology of MI in elderly patients remains an important issue for the future planning of the healthcare system.

Introduction: Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients., Methods: Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke., Results: In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031)., Conclusions: High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.

Objective and Methods: The impact of the rs9939609 FTO variant on cardiovascular events was investigated in the 19-year follow-up of subjects recruited to the OPERA study., Results: A total of 212 cardiovascular disease (CVD) and 152 coronary heart disease (CHD) events or deaths occurred during follow-up. The logistic regression analysis revealed that among the AA genotype the incidence of CHD (OR 1.905; 95% CI 1.250-2.903, p = 0.001) and CVD (OR 1.849; 1.265-2.702, p = 0.003) events or death was significantly higher when adjusted for age, sex, and study group. After further adjustment with BMI, smoking status, systolic blood pressure, and low-density lipoprotein cholesterol, the higher incidence of CHD and CVD events or death among subjects with the AA genotype remained significant (OR 1.895; p = 0.002 and p = 0.004, respectively). In Cox regression analysis, the AA genotype displayed a higher rate of CVD and CHD death when the model was adjusted for sex, age, and study group (p = 0.006 and p = 0.046). FTO rs9939609 AA genotype improved the C-index of the final predictive model from 0.709 to 0.715. In reclassification analyses, the integrated discrimination index was significant 0.011 (p = 0.010)., Conclusion: The AA genotype of FTO rs9939609 seems to be associated with a higher risk of CVD, and this phenomenon seems to be independent of the traditional risk factors for atherosclerosis.

Aim: Obesity and type 2 diabetes (T2D) associate with increased oxidative stress. Malondialdehyde acetaldehyde (MAA) adducts have been suggested to be one of the antigenic epitopes in MDA-LDL responsible for the antibody recognition. Our aim was to investigate the associations between plasma IgA antibodies to MAA-LDL, inflammatory markers, adipokines, obesity, and T2D., Methods: IgA to MAA-LDL were measured in a subsample (n = 1507) of the Finnish Health 2000 survey. The associations between antibody levels, obesity, TNF-α, IL-6, high-sensitivity (hs) CRP, resistin, adiponectin, fasting plasma (fp) glucose, fp-insulin, glycosylated hemoglobin (Hb-A1C), and T2D were investigated., Results: IgA to MAA-LDL associated positively with fasting plasma insulin. IgA to MAA-LDL were higher among subjects with T2D (P < 0.001) compared to subjects with normal glucose metabolism. IgA to MAA-LDL associated with obesity, but was not independently (P = 0.002, not significant after correction for multiple tests) associated with T2D in logistic regression analysis. IgA to MAA-LDL, obesity, and TNF-α all associated with markers of glucose metabolism., Conclusions: T2D subjects had increased IgA to MAA-LDL compared to subjects with normal glucose metabolism. The data suggest that the associations between IgA to MAA-LDL and markers of glucose metabolism were independent of TNF-α but dependent on components of the metabolic syndrome.

Objective and Methods: The correlation between total testosterone levels, exercise capacity, and metabolic and echocardiographic parameters was studied in 1097 male subjects with coronary artery disease (CAD) and different stages of glucose tolerance., Results: Testosterone level was the lowest among diabetics as compared to prediabetics or controls (P < 0.001). Total and abdominal adiposity were the highest in the subjects with the lowest testosterone. Independent of adiposity, fasting glucose, insulin, and leptin were higher (P < 0.03 to < 0.001) among diabetic and control groups in the lowest, and HbA1c values (P < 0.001) higher among diabetics in the lowest, than in the highest testosterone tertile. Controls and prediabetic subjects with the lowest testosterone levels had the lowest HDL-cholesterol levels, and controls also the highest triglycerides. An association between low testosterone level and low maximal exercise capacity was observed in diabetics (P < 0.001) and controls (P < 0.03). Independent of adiposity and metabolic parameters, low testosterone levels were associated with the highest septal wall thickness (P < 0.03) among diabetics., Conclusion: A negative correlation between low testosterone and dysmetabolic features was observed. Independent of metabolic status, low plasma testosterone seems to be an indicator of impaired maximal exercise capacity and cardiac hypertrophy among CAD patients with type II diabetes.

Aims: We investigated the association between daily sodium intake and each individual component of the metabolic syndrome (MS) as well as the metabolic cluster per se and clarified which of the combinations of MS features is particularly associated with sodium intake., Methods: A total of 716 subjects from our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort were selected to fill in a food follow-up diary for a 1-week period. The MS was determined using the International Diabetes Federation (IDF) criteria., Results: Subjects with the MS used more sodium (P < 0.001), less carbohydrate (P < 0.001), less fibre (P = 0.031), and more alcohol (P < 0.001) than those without the MS. High sodium intake was strongly related to elevated BMI (P = 0.003), waist (P < 0.001), and higher fasting blood glucose (P < 0.001). The subjects with the highest sodium intake suffered more often from type 2 diabetes (P = 0.007). Sodium intake was highest in the group where all the MS criteria were present (P < 0.001). High sodium intake was a statistically significant predictor of the MS in logistic regression analysis (P = 0.009). The highest sodium intake was observed in the IDF criteria combination waist + glucose + blood pressure., Conclusions: These findings suggest that a reduction in sodium intake may be especially beneficial in the treatment of individuals with the MS.

Background: A low adiponectin level is associated with high blood pressure which, in turn, often results in left ventricular hypertrophy. We evaluated the association between plasma adiponectin concentrations and echocardiographic measurements, including left ventricular mass index (LVMI), in 933 middle-aged subjects consisting of 453 hypertensives and 480 controls., Methods: Plasma adiponectin concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) method. One experienced cardiologist performed echocardiographic examinations, and LVMI was calculated according to Devereux's method., Results: Low plasma adiponectin levels were independently associated with increased intraventricular septum thickness, posterior ventricular wall thickness, and left ventricular mass index (P<0.001) in the whole cohort. In the subgroup analysis, the association between these echocardiographic parameters and adiponectin concentrations was observed only in the hypertensive cohort although fractional shortening revealed an association with adiponectin levels also in the control cohort (P=0.021). Findings remained significant after adjustment for the major risk factors for LVMI, such as age, sex, smoking, and systolic blood pressure., Conclusions: This study in a large population sample detected an association between low plasma adiponectin concentration and LVMI, a marker of left ventricular hypertrophy. This association may be one of the factors that could explain the reported increased cardiovascular risk in subjects with low adiponectin levels.

Background: High leptin and low ghrelin are associated with the metabolic syndrome (MS)., Aims and Methods: Ghrelin, leptin (RIA kits), and insulin-like growth factor I (IGF-I) (ELISA kit) concentrations of the population-based cohort of 1045 subjects and their interactions with metabolic parameters were analysed. Intima-media thickness (IMT) was measured with carotid ultrasound., Results: The interaction between leptin and ghrelin on the MS was significant (P = 0.011). An additive effect of high leptin and low ghrelin on metabolic disturbances was observed: low ghrelin concentration (adjusted for age and sex) (P < 0.001) was associated with the MS and type 2 diabetes in the highest but not in the lower leptin quartiles. In the highest leptin quartile, ghrelin concentrations decreased linearly when the number of International Diabetes Federation MS criteria met (P < 0.01) increased. Ghrelin-leptin relation was independently associated with carotid IMT (P < 0.005). The independent positive association (P < 0.01) between the plasma ghrelin quartile and the carotid IMT was evident in the lowest IGF-I quartile., Conclusions: Low ghrelin is associated with MS and type 2 diabetes in the presence of insulin and leptin resistance. Ghrelin-leptin relation is associated with early atherosclerosis. The interaction between IGF-I and ghrelin modifies the association of ghrelin with early atherosclerosis.

Background: Low ghrelin concentration has been associated with several features of metabolic syndrome (MS), but the relationship between ghrelin concentration and MS as a cluster of metabolic aberrations has not yet been studied., Aims of the Study: To analyse whether ghrelin concentration is associated with MS., Research Design and Methods: Fasting plasma ghrelin concentrations of the population-based cohort of 1037 middle-aged men and women were analysed using a commercial radioimmunoassay kit (Phoenix Peptide). MS was determined using the new International Diabetes Federation criteria., Results: The prevalence of MS was 37.2%. The ghrelin concentrations were decreased in subjects with MS (635 pg/mL) compared to those without MS (687 pg/mL) (P=0.001). Ghrelin levels decreased with an increase in the number of metabolic abnormalities. Low ghrelin was a statistically significant predictor of MS in logistic regression analysis (P=0.005) so that the subjects in the 1st ghrelin quartile were at higher risk of having MS compared to the subjects in the 4th quartile (OR=1.82, 95% CI: 1.27-2.60, P=0.001). This association remained statistically significant after adjustment for age and sex (OR=1.76, 95% CI: 1.24-2.55, P=0.002)., Conclusions: Metabolic syndrome is associated with low ghrelin levels suggesting a relationship of ghrelin in the metabolic disturbances of MS.

Aims/hypothesis: Adiponectin is an adipocytokine with lowered blood levels in obesity and Type 2 diabetes mellitus. We sought to define the specific effects of different alleles of the gene encoding adiponectin., Methods: We studied the associations of adiponectin gene sequence variations with body fat distribution and insulin indices in 503 White and 276 Black subjects of the HERITAGE Family Study cohort and subjects from a Finnish population., Results: The His111 allele frequency of the Tyr111 His polymorphism in Finnish Type 2 diabetic subjects (n=254) was higher (5.1%) than in control subjects (n=270) (2.6%; P = 0.033). In the HERITAGE cohort, the His111 allele was associated with a lower insulin sensitivity index (P = 0.018) and a higher acute insulin response to glucose (P = 0.0098) in Whites. Other variants showed associations with adiposity and plasma lipid values only in Blacks. Among Blacks, the IVS2+G62T variant was associated with body fat (P = 0.002) and total cholesterol values (P = 0.005), and the Gly15Gly variant with cholesterol (P = 0.009) and triglyceride (P = 0.05) levels. The haplotype derived from these two polymorphisms was associated with total body fat, while the IVS2+G62T and Tyr111His-haplotype was associated with body fat and disposition index., Conclusions: The carriers of the His111 allele may have a higher risk of developing Type 2 diabetes mellitus. Racial differences were found between Blacks and Whites in body composition and lipids according to ACDC genotypes. Sequence variants in the adiponectin gene appear to be associated with diabetes and diabetes-related phenotypes.

Background: Alterations in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF-I levels., Aims: To investigate whether IGF-I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery., Methods: Fasting plasma IGF-I concentrations (n=1008) were measured in a large population-based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method., Results: Low IGF-I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C-reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF-I concentrations were positively associated with the mean IMT of women (ss=0.127, P=0.009) whereas the association in men was weaker and negative (ss=-0.088, P=0.034). The 1169A allele was associated with low low-density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women., Conclusions: IGF-I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF-I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.

Aim: This research was designed to study the temporal changes in cardiovascular autonomic regulation, assessed by 24-hour heart rate (HR) variability, and the possible relation of changes in HR variability to cardiovascular risk factors and progression of coronary artery disease (CAD) among type II diabetic subjects., Method: In a single-center substudy of The Diabetes Atherosclerosis Intervention Study (DAIS), 53 patients assigned to fenofibrate (n = 26) or placebo (n = 27), underwent time and frequency domain and fractal analysis of HR variability, coronary risk variable analyses and quantitative coronary angiograms at baseline and after three years' follow-up., Results: Twenty-four hour standard deviation of sinus intervals (SDNN) decreased from 113 +/- 35 to 94 +/- 30 msec (P < 0.001) during the three year period. Low frequency power spectral component and short-term fractal scaling exponent also decreased (P < 0.001 and P < 0.05, respectively). The reduction of SDNN was weakly related to a change in the triglyceride level (r = -0.33, P < 0.05), glucose level (r = -0.28, P < 0.05) and total cholesterol concentration (r = -0.35, P < 0.01). Furthermore, the reduction of SDNN was related to a decrease in the minimum lumen and mean segment diameter of the coronary arteries (r = 0.36, P < 0.01, and r = 0.39, P < 0.01, respectively). This association was more marked in the placebo group (r = 0.50, P < 0.01 and r = 0.44, P < 0.05, respectively) than among the patients randomized to fenofibrate (not significant for both)., Conclusions: Cardiovascular autonomic regulation assessed by HR variability deteriorates rapidly in type II diabetic subjects with CAD during the time course. Impairment in HR variability is associated with changes in common coronary risk variables and with a progression of CAD.

The objective of this paper is to review the current evidence of a novel gastric hormone ghrelin. Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) that potently stimulates growth hormone (GH) release. The discovery of ghrelin opens up a new regulatory system for the GH secretion. Surprisingly, recent studies in rodents suggest that peripherally or centrally administrated ghrelin, independent of GH, decreases fat oxidation and increases food intake and adiposity. In addition, plasma ghrelin levels are lower in obese human subjects. Ghrelin might participate in meal initiation and may signal to the hypothalamus when an increase in the metabolic efficiency is needed. However, the role of ghrelin in the regulation of body weight in humans is unknown. Whether ghrelin's somatotrophic effect surpasses its adipogenic effect in the prolonged administration determines its effect on energy balance. New interesting implications for ghrelin have recently been suggested. For instance, ghrelin's cardiovascular effects might have clinical relevance. Furthermore, ghrelin might be involved in the growth of some neoplasms. In conclusion, ghrelin, a new somatotrophic, orexigenic and adipogenic peptide hormone, links the regulatory systems for growth and energy balance.

The objective of this paper is to review the current evidence in support of genetic factors underlying the clustering of components of the metabolic syndrome in obese individuals. It has become clear that individual features of the metabolic syndrome are partially determined by familial factors some of which are unique to a given component and others that are shared among several features. A few candidate genes, encoding proteins of glucose, insulin and lipid metabolism, lipolytic cascade, fatty acid intestinal absorption, glucocorticoid metabolism, haemostasis and blood pressure, have been associated with a clustering of metabolic abnormalities, although the functional significance of these associations remains to be established. Furthermore, genetic polymorphisms, such as those detected at several lipoprotein metabolism loci, can modulate the relationships between different components of the metabolic syndrome. An overfeeding study conducted on identical twins has demonstrated that genetic factors play an important role in the responsiveness to changing energy balance conditions. Leptin receptor, beta2 adrenergic receptor and glucocorticoid receptor gene polymorphisms have been associated with an augmented clustering of metabolic abnormalities in response to overfeeding. Gene-gene interaction effects between markers of the alpha2A, beta2 and beta3 adrenergic receptor genes on components of the metabolic syndrome have been described. Genetic factors also seem to modify the responsiveness of metabolic syndrome features to endurance training. A growing understanding of the genetic architecture of the metabolic syndrome may help in the prevention of this condition. The reduction of excess body fat, the most common clinical feature among the cluster of metabolic abnormalities, should be the focus of the prevention and treatment of the metabolic syndrome.