Dietary sodium intake and prediction of cardiovascular events.

BACKGROUND/OBJECTIVES: The association of dietary sodium and cardiovascular disease (CVD), as well as the reduction of sodium intake in the prevention of CVD, has been under debate. To study whether sodium consumption has a role as a risk factor for fatal and non-fatal CVD. SUBJECTS/METHODS: A well-defined population-based cohort of 1045 subjects collected between 1991 and 1993 (mean age 51.4 years) was used with approximately 19 years' follow-up. At the baseline, 716 subjects filled in a 1-week food follow-up diary, which was used to calculate the daily sodium intake (mg/1000 kcal). RESULTS: The baseline sodium intake correlated significantly with age (rs=0.117, P=0.002), BMI (rs=0.216, P=0.000), waist circumference (rs=0.268, P=0.000), smoking (rs=0.144, P=0.000), alcohol consumption (rs=0.111, P=0.003), systolic blood pressure (rs=0.106, P=0.005) and low-density lipoprotein (LDL) cholesterol (rs=0.081, P=0.033). Those who had cardiovascular events in the follow-up consumed more sodium at the baseline (mean 2010.4 mg/1000 kcal/day, s.d. 435.2, n=101) compared with the subjects without events (mean 1849.9 mg/1000 kcal/day, s.d. 361.2, n=589; t-test; P=0.001). The incidence of cardiovascular events was greater in the highest quartile (22.1%) than in the lower quartiles (first 11.0%, second 9.9% and third 15.6%; X(2); P=0.005). Cox regression analysis showed that sodium intake as a continuous variable predicts CVD events (P=0.031) independently when age, sex, smoking, alcohol consumption, systolic blood pressure, LDL cholesterol and waist circumference were added as covariates. This predictive role is seen especially in the group of subjects on hypertensive medication (P=0.001). CONCLUSIONS: Dietary sodium intake is a significant independent predictor of cardiovascular events in the study population.

High plasma ghrelin protects from coronary heart disease and Leu72Leu polymorphism of ghrelin gene from cancer in healthy adults during the 19 years follow-up study.

The aim of our investigation was to find out if ghrelin concentrations or polymorphisms predict the future risk for cardiovascular diseases and cancer in a population-based cohort initiated in 1991 (491 hypertensive and 513 control subjects). Total mortality and hospital events were followed up for 19 years. Fasting total ghrelin concentrations were determined and Arg51Gln, Leu72Met and -501 A > C polymorphisms identified. Cox regression analysis was performed. The mean value in the control cohort was 674 pg/ml whereas in the hypertensive cohort it was 661 pg/ml. The associations found suggest that in the controls the highest ghrelin quartile protected from CHD (coronary heart disease). The results were significant without or with adjustments for age, sex, smoking, systolic blood pressure and LDL cholesterol, BMI, type 2 diabetes or QUICK index. C/C variant of the promoter associated with the prevention of IHD (ischemic heart disease) in the hypertensive group (p<0.05). The controls with the Leu72Leu genotype had less cancer (p<0.05). In conclusion, high plasma ghrelin concentration was related to protection from CHD and Leu72Leu genotype to prevention of cancer in healthy adults during the 19 years follow-up. C/C promoter protects from IHD in the hypertensive subjects.

Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis.

BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by ß-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful.

Ghrelin and its promoter variant associated with cardiac hypertrophy.

The roles of ghrelin, a peptide hormone that has a role in regulating food intake and energy homeostasis, in the cardiovascular system have not yet been unambiguously established. We evaluated the association between plasma ghrelin concentrations and -501A>C single-nucleotide polymorphism (SNP) in the ghrelin gene 5' flanking area and echocardiographic measurements in 1037 middle-aged subjects. Left ventricular mass index (LVMI) was calculated according to Devereux's method. The ambulatory blood pressure (BP) was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Results suggested that plasma ghrelin was not related to mean ambulatory BP values. However, the highest plasma ghrelin tertile was associated with increased intraventricular septum (P=0.043) and posterior ventricular wall (P=0.002) thicknesses as well as left ventricular mass (P=0.05). After adjustment for age, sex, body mass index and systolic BP, the association persisted between ghrelin tertiles and intraventricular septum (P=0.05) and posterior ventricular wall (P=0.001) thicknesses. The SNP -501A>C polymorphism was associated with LVMI after adjustments for age, sex and systolic BP. In conclusion, ghrelin and its promoter variant are associated with cardiac hypertrophy indexes independent of BP. Positive correlation between ghrelin levels and increased wall thickness parameters may reflect compensatory up-regulation of ghrelin concentrations or direct effects of ghrelin on myocardium. The effects of the SNP seem not to be mediated through its effects on ghrelin plasma levels.

Pentraxin 3 (PTX3) is associated with cardiovascular risk factors: the Health 2000 Survey.

Pentraxin 3 (PTX3) is a novel candidate immunoinflammatory marker that has been reported to be associated with cardiometabolic risk factors and to predict adverse outcomes in individuals with cardiovascular disease (CVD). Despite being a member of the same pentraxin protein family as C-reactive protein (CRP), PTX3 probably reflects different aspects of CVD pathogenesis. In this study, we assessed plasma PTX3 correlates and determinants in the Health 2000 Survey population, which comprised n = 403 insulin-resistant subjects, n = 845 hypercholesterolaemic subjects and n = 311 hypertensive subjects, all aged between 46 and 76 years. In insulin-resistant subjects the PTX3 concentration was found to correlate directly with age, pulse pressure and indoleamine 2,3-dioxygenase (IDO) enzyme activity and inversely with total and low-density lipoprotein (LDL) cholesterol. In hypercholesterolaemic subjects, the PTX3 concentration correlated directly with HDL cholesterol, systolic blood pressure and pulse pressure, whereas in hypertensive subjects, the PTX3 concentration correlated directly with systolic blood pressure, pulse pressure and IDO activity. No correlation was observed between the concentrations of PTX3 and CRP, adiposity indicators or indicators of subclinical atherosclerosis in any of the subject groups. PTX3 concentration variations were attributed to variations in LDL cholesterol and IDO activity in insulin-resistant subjects and to pulse pressure in hypercholesterolaemic and hypertensive subjects. These results indicate that, in individuals at high risk of CVD, the PTX3 concentration is associated with cardiovascular risk factors but not with subclinical atherosclerosis.

Associations between interleukin-1 (IL-1) gene variations or IL-1 receptor antagonist levels and the development of type 2 diabetes.

OBJECTIVES: To examine whether interleukin-1 receptor antagonist (IL-1Ra) is a predictor for clinically incident diabetes in subjects with metabolic syndrome (MetS) and whether its predictive power is independent of C-reactive protein (CRP), an established marker of inflammation. We further examined whether genetic variants at the interleukin-1 (IL-1) locus would predict clinically incident diabetes. DESIGN: Two observational prospective cohort studies. SETTING: Two separate cohorts, Health 2000 and FINRISK 1997, followed up for an average of 7.1 and 10.8 years, respectively. SUBJECTS: Random population samples consisting of 5511 subjects aged 30-74 years in Health 2000 and 7374 subjects aged 25-74 years in FINRISK 1997. RESULTS: During follow-up, 141 cases of clinically incident diabetes were observed amongst subjects with MetS at baseline in Health 2000 and 248 cases in FINRISK 97. After adjustment for multiple traditional risk factors of diabetes, including age and body mass index, IL-1Ra was a significant (P < 0.01) predictor of incident diabetes amongst men in both cohorts and amongst women in FINRISK 1997. Further adjustment for CRP reduced the hazard ratios only slightly. Genetic analyses produced nominally significant associations for three single-nucleotide polymorphisms: rs3213448 in IL-1 receptor antagonist (IL1RN), rs1143634 in IL-1 beta (IL1B) and rs1800587 in IL-1 alpha (IL1A). The two latter variants had an interaction with gender (P = 0.023 and 0.002, respectively) suggesting the presence of gender-specific associations with the risk of clinically incident diabetes. CONCLUSIONS: IL-1Ra predicted the progression of MetS to clinically incident diabetes independently of CRP and other risk factors. Genetic variation in the IL-1 locus may have gender-specific associations with the risk of type 2 diabetes.

Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study.

AIMS/HYPOTHESIS: Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. METHODS: Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. RESULTS: During fenofibrate run-in, plasma creatinine increased by 10.0 µmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 µmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min(-1) 1.73 m(-2) annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min(-1) 1.73 m(-2), p = 0.065) than on placebo (6.9 ml min(-1) 1.73 m(-2), p < 0.001), sparing 5.0 ml min(-1) 1.73 m(-2) (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥ 0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% [95% CI 9-18]; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). CONCLUSIONS/INTERPRETATION: Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. TRIAL REGISTRATION: ISRCTN64783481.

Serum ghrelin and the prediction of the development of impaired glucose regulation and Type 2 diabetes in middle-aged subjects.

BACKGROUND: Ghrelin is a peptide hormone which has been shown to associate with obesity, hypertension and Type 2 diabetes (T2DM) in cross-sectional studies. AIM: To study whether total ghrelin levels have predictive value for the incidence of impaired glucose regulation (IGR) or T2DM. SUBJECTS AND METHODS: The subjects of this prospective follow-up study (no.=201) belonged to a population-based cohort collected in Northern Finland. Oral glucose tolerance tests (OGTT) and measurements of fasting serum total ghrelin, lipids, blood pressure and body mass index were performed at the beginning and at the end of the study. The mean follow-up time was 5.1 yr. The subjects had normal glucose tolerance (NGT) at the beginning of the study. RESULTS: T2DM developed in 6 (3%), impaired fasting glucose (IFG) in 6 (3%) and impaired glucose tolerance (IGT) in 35 (17.4%) subjects. The baseline ghrelin concentrations did not differ between the two studied groups: median fasting serum total ghrelin concentration was 733 pg/ml (25th-75th percentiles: 571-961 pg/ml) among those who maintained NGT, and 661 pg/ml (25th-75th percentiles: 527- 878 pg/ml) among those who developed IGR (IFG and/or IGT) or T2DM (p=0.421). The baseline ghrelin concentrations did not explain the changes in the 0-h or 2-h blood glucose concentrations in regression models. CONCLUSIONS: Our findings suggest that fasting serum total ghrelin levels measured at one time point might not have predictive value for the development of abnormalities in glucose tolerance.

Glomerular filtration rate is related to dipping pattern in ambulatory blood pressure monitoring--a cross-sectional population-based study.

A non-dipping pattern in ambulatory blood pressure monitoring (ABPM) increases the risk of cardiovascular disease. The association between renal function and the dipping pattern has not been studied in a random middle-aged population. This is a cross-sectional population-based study of 226 males and 234 females aged 40 to 62 years. Renal function was assessed with estimated glomerular filtration rate (eGFR). Non-dipping status was defined as a reduction of <10% between the daytime and the nighttime systolic BP. Non-dippers represented 18.7% of the study population. Their mean eGFR was 79.1 (s.d. 15.7) ml min(-1) per 1.73 m(2) as compared with a mean eGFR of 84.1 (s.d. 16.2) ml min(-1) per 1.73 m(2) in dippers (P=0.005); this difference remained significant after adjustments. Subjects in the lowest and in the middle eGFR tertiles had an independently increased risk of non-dipping in comparison with those in the highest eGFR tertile (odd ratios (OR), 2.34 (95% confidence interval (CI), 1.18 to 4.63) and OR, 2.01 (95% CI, 1.06 to 3.83), respectively). This study showed that even a minor deterioration in renal function is associated with increased risk of non-dipping pattern in ABPM in a random middle-aged population.

Plasma adiponectin concentration is associated with ambulatory daytime systolic blood pressure but not with the dipping status.

The objective of this study was to analyse the relationship between the ambulatory blood pressure (ABP) measurement and plasma adiponectin levels in a population-based cohort. Non-hypertensive, non-diabetics from the Oulu Project Elucidating Risk of Atherosclerosis cohort aged 40-60 years with ABP measurement available in 226 men and 236 women were analysed. ABP was recorded using the fully automatic SpaceLabs 90207 oscillometric unit. Plasma adiponectin concentrations were assayed using the enzyme-linked immunosorbent assay method. Without adjustment the highest plasma adiponectin tertile was associated with the lowest ABP and office BP measurements (P from 0.025 to P<0.001, respectively). Only the association of plasma adiponectin concentration with systolic ABP was independent of other conventional risk factors (age, body mass index (BMI), waist, gender, insulin sensitivity index, smoking and alcohol consumption) for hypertension (P=0.017). No association was observed between systolic dipping pattern and adiponectin level. The plasma high adiponectin concentration is independently associated with low daytime systolic ABP value. The mechanisms may include effects on endothelial function and the sympathetic nervous system.

Early atherosclerosis and IgG2 to bacteria are associated with FcgammaRIIa genotype in non-smokers.

BACKGROUND: Involvement of low density lipoprotein (LDL) immune complexes (ICs) in atherogenesis has been proposed. Human FcgammaRIIa receptor (CD32) plays a crucial role in the phagocytosis of IgG(2) ICs and a functional point mutation 131His/Arg diminishes IgG(2) binding to the receptor. STUDY DESIGN: We examined FcgammaRIIa-131His/Arg polymorphism, IgG(2) antibody titres to oxidized low-density lipoprotein (OxLDL) and Streptococcus pneumoniae cell wall polysaccharide (CWPS) and subclinical atherosclerosis in a large cohort of Finnish subjects (n = 1041). RESULTS: Non-smoking subjects with homozygous 131His/His genotype had more premature atherosclerosis (P = 0.004) and higher IgG(2) to bacterial CWPS (P = 0.002) compared with other genotypes. Smoking subjects had significantly higher intima-media thickness (IMT) than that of non-smokers (P < 0.001) and genotype-dependent associations were indistinct. There was no association between FcgammaRIIa genotype and antibody titres to OxLDL. CONCLUSIONS: Our data demonstrate that FcgammaRIIa 131His/Arg polymorphism is associated with subclinical atherosclerosis in non-smoking subjects. Furthermore, FcgammaRIIa genotype is associated with IgG(2) titres to bacterial CWPS, but not to OxLDL. These data propose possible involvement of FcgammaRIIa receptor in atherogenesis.

Pre-eclampsia is a risk factor of carotid artery atherosclerosis.

BACKGROUND: A history of pre-eclampsia has been shown to be associated with an increased risk of subsequent coronary artery disease. The intima-media thickness of carotid arteries and the detection of plaques are useful measures as regards preclinical atherosclerosis. The aim of this study was to examine whether women with a history of pre-eclampsia more often show signs of atherosclerosis compared with 2 control groups. METHODS: We used data from a large Finnish cross-sectional health examination survey. We had women with previous pre-eclampsia (n = 35) or pregnancy-induced hypertension (n = 61) and 2 control groups. Laboratory tests and physical examination were performed. Information on reproductive and medical history was obtained at the home interview. Carotid atherosclerosis was assessed by ultrasonography. RESULTS: The women with previous pre-eclampsia had significantly (p = 0.008) more atherosclerotic plaques than the healthy parous controls. The intima-media thickness in the women with previous pre-eclampsia also tended to be higher than in the other groups, although the differences did not reach statistical significance. In logistic regression analysis, advanced age (OR: 1.08; 95% CI: 1.04-1.13; p < 0.001) and pre-eclampsia (OR: 3.63; 95% CI: 1.50-8.79; p = 0.004) were independent risk factors as regards plaque, and in linear regression analysis advanced age (estimate: 0.012; 95% CI: 0.010-0.014; p < 0.001), HDL cholesterol (estimate: -0.049; 95% CI: -0.088 to -0.010; p = 0.013), systolic blood pressure, BMI (estimate: 0.005; 95% CI: 0.000-0.009; p = 0.043) and high-sensitivity C-reactive protein (estimate: -0.003; 95% CI: -0.007 to -0.000; p = 0.048) were independent risk factors with respect to intima-media thickness. CONCLUSIONS: Our data suggest that pre-eclampsia is an independent risk factor as regards developing plaque later in life.

Leptin and lipid metabolism in chronic kidney failure.

OBJECTIVE: In the general population, leptin has been associated with atherosclerosis and has been shown to interfere with lipoprotein profiles. Patients with chronic renal failure are at increased risk of cardiovascular disease and display alterations in both lipoprotein and leptin levels. The aim of this study was to investigate the relationship between leptin and the lipoprotein profile in non-dialyzed patients with chronic kidney disease (CKD). MATERIAL AND METHODS: Leptin and lipid and lipoprotein concentrations were studied in 73 CKD patients and in 68 healthy controls in a cross-sectional case-control design. RESULTS: The mean leptin levels were increased in the CKD patients (24.0 (SD 37.1) ng/mL) compared to those in controls (9.0 (SD 8.5) ng/mL) (p = 0.008). Also, the ratio between leptin levels and body mass index (leptin/BMI) was increased in CKD patients (mean 0.80 (SD 1.03)) compared to that in controls (0.31 (SD 0.24)) (p = 0.001). In linear regression analysis, leptin independently predicted total cholesterol and triglycerides in CKD patients (p = 0.010 and p = 0.001, respectively) and ratio between total and HDL cholesterol (Chol/HDL) in controls (p = 0.024). Furthermore, in CKD patients, the leptin/BMI predicted the variation in total cholesterol and triglycerides (p = 0.010 and p = 0.002, respectively). CONCLUSIONS: Leptin concentrations and leptin/BMI were elevated in CKD patients compared to those in controls. Leptin levels in both study groups, and leptin/BMI in the CKD group, were associated with atherogenic lipid profiles, which may contribute to the elevated cardiovascular risk that has been linked to hyperleptinaemia.

ApoE phenotype is associated with inflammatory markers in middle-aged subjects.

OBJECTIVES: Apolipoprotein (apo) E phenotype has been associated with inflammation markers. The determinants of these associations and the relationship between novel inflammation marker, resistin, and apoE phenotype are studied here. METHODS AND RESULTS: Middle-aged subjects of the population- based cohort (n = 526) of the OPERA- study were studied. Intima-media thickness (IMT) was measured with carotid ultrasound. The results suggest that, apoE phenotype was a significant independent predictive factor for resistin (p < 0.01) and hsCRP (p < 0.01) levels. The association of ApoE phenotype with hsCRP was seen among the subjects with the normal renal function (p = 0.005). ApoE4 was associated (p < 0.01) with the lowest hsCRP in the lowest IMT quartile while it's relation with the highest resistin levels was evident in the highest IMT quartile. CONCLUSIONS: ApoE phenotype is an independent determinant of plasma resistin and hsCRP levels. The extent of atherosclerosis and renal function seem to modify the effects of apoE phenotype on inflammatory parameters.

Indoleamine 2,3-dioxygenase activity associates with cardiovascular risk factors: the Health 2000 study.

Indoleamine 2,3-dioxygenase (IDO) is an important immunomodulator suppressing the activation of T lymphocytes, and its level in blood is increased in several autoimmune and inflammatory diseases. We have previously shown that this activity associates with several signs and risk factors of atherosclerosis in 24 to 39-year-old females. Now we repeat this analysis in an older population (n = 921, age range 46-76 years), i.e. in a population with more advanced atherosclerosis. IDO activity had a significant positive correlation in both sexes with carotid artery intima/media thickness (IMT), an early marker of atherosclerosis. In females, a significant negative correlation with HDL cholesterol and a positive correlation with triglycerides levels was observed. The association with IMT did not remain significant after adjustment with classical risk factors of atherosclerosis. It is thus concluded that IDO is a sensitive marker of atherosclerosis--or the inflammatory response associated with it--but does not have an independent role in the pathogenesis of this disease.

Risk of dementia associated with the ApoE epsilon4 allele and falls causing head injury without explicit traumatic brain injury.

OBJECTIVES: Severe head injury (HI) and the apolipoprotein E (ApoE) epsilon4 allele are risk factors for dementia. The corresponding effect of falls causing HI without explicit traumatic brain injury (TBI) in association with the ApoE epsilon4 is not known. MATERIALS AND METHODS: Altogether 134 persons aged 70 years or older constituted a retrospective population sample, who scored > or =26 in the MiniMental State Examination (MMSE) test at baseline and were clinically examined for dementia 9 years afterward. Fall-related HI causing superficial laceration or bruises or wounds that require suturing were prospectively recorded during the 9-year follow-up. We used Cox regression with age at the diagnosis of dementia as a dependent variable. RESULTS: Twenty-eight (21%) subjects had falls causing HI without explicit TBI, the ApoE epsilon4 allele was seen in 44 (33%), and clinical dementia was diagnosed in 25 (19%). Adjusted for the baseline MMSE score, sex and educational status, the hazard ratio for subsequent dementia in subjects having falls with HI without explicit TBI and the ApoE epsilon4 allele as compared with those who do not possess these characteristics was 2.70 (95% confidence interval, 1.02-7.16). CONCLUSIONS: According to the results of this small retrospective study, falls with HI without explicit TBI in connection with the ApoE epsilon4 allele is associated with subsequent dementia among older adults.

Leu7Pro polymorphism of PreproNPY associated with an increased risk for type II diabetes in middle-aged subjects.

OBJECTIVES: Neuropeptide Y (NPY) plays a central in energy homeostasis and potentially in the development of obesity-related comorbidities, like type II diabetes. As the PreproNPY Leu7Pro polymorphism probably changes the intracellular processing of the synthesized preproNPY peptide, we assessed the hypothesis that PreproNPY Leu7Pro polymorphism is a risk factor for type II diabetes, impaired glucose tolerance and hypertension. DESIGN: Blood pressure recordings and oral glucose tolerance test were performed in the hypertensive (n=515) and control cohorts (n=525) of our well-defined Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study. The prevalence of type II diabetes was 9% (n=93). The genotypes, insulin and glucose metabolism indexes and plasma ghrelin of the subjects were determined. RESULTS: Pro7 allele frequencies were 5.9, 5.3 and 11.3% in the total cohort, in subjects without and with type II diabetes, respectively. The PreproNPY Pro7 carrier status was a significant risk factor for type II diabetes, and the effect remained significant after adjustment for age, sex, waist circumference and study group (odds ratio=3.02, confidence interval: 1.67-5.44 and P<0.001). Pro7 carriers were more insulin resistant and showed lower ghrelin levels compared to non-carriers. CONCLUSIONS: The PreproNPY Pro7 allele is associated with an increased risk for type II diabetes. The risk seems to be associated with a higher insulin resistance among Pro7 carriers whereas low ghrelin concentrations in Pro7 carriers are possibly a consequence of high insulin levels.

Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study.

OBJECTIVE: Abdominal obesity, insulin resistance and compensatory hyperinsulinaemia play a central role in the pathogenesis of the polycystic ovary syndrome (PCOS). Abdominal adipose tissue is a source of adipokines, such as adiponectin and resistin, both of which may be involved in the development of insulin resistance and chronic inflammation in PCOS. Ghrelin, an important regulatory peptide of food intake, may also play a role in metabolic disturbances related to PCOS. The aim of this study was to examine the effects of 4 months of treatment with the insulin sensitizer rosiglitazone on plasma adiponectin, resistin and ghrelin levels in overweight women with PCOS. DESIGN: A randomised placebo-controlled study. METHODS: Thirty overweight/obese women with PCOS (body mass index>25 kg/m(2), mean age 29.1+/- 1.2 (S.E.M.) years) were randomly allocated to either rosiglitazone (Avandia, 4 mg twice a day) or placebo treatment. Plasma levels of adiponectin, resistin and ghrelin and their correlation to serum levels of insulin, C-peptide and steroid hormones, and insulin sensitivity (euglycaemic hyperinsulinaemic clamp) were assessed. RESULTS: Adiponectin and ghrelin levels correlated significantly with most metabolic markers of insulin resistance and with serum levels of DHEA and 17-hydroxyprogesterone. Plasma levels of adiponectin increased from 9.26+/-0.90 (S.E.M.) to 22.22+/-3.66 microg/ml (P<0.001) and those of resistin decreased from 12.57+/-1.63 to 9.21+/-0.53 ng/ml (P=0.009) at 4 months of treatment, but plasma ghrelin levels did not change. CONCLUSIONS: Rosiglitazone had beneficial effects on serum levels of adiponectin and resistin, suggesting that these adipocytokines may contribute to the improvement in insulin sensitivity observed during the treatment.

Association of metabolic syndrome with Alzheimer disease: a population-based study.

OBJECTIVE: To assess the association of metabolic syndrome (MetS) with Alzheimer disease (AD). METHODS: The authors derived subjects from a population-based study of 980 randomly selected elderly subjects. After exclusion of all non-Alzheimer dementia cases, the final study population included 959 subjects (337 men and 622 women) aged 69 to 78 years. The presence of MetS was defined according to the National Cholesterol Education Program (Adult Treatment Panel III) criteria, and the diagnosis of AD was based on the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Of the study subjects, 418 (43.6%) had MetS. Probable or possible AD was diagnosed in 45 subjects (4.7%). AD was more frequently detected in subjects with MetS than in subjects without MetS (7.2 vs 2.8%; p < 0.001). The prevalence of AD was higher in women with MetS vs women without the syndrome (8.3 vs 1.9%; p < 0.001), but in men with MetS, the prevalence of AD was not increased (3.8 vs 3.9%; p = 0.994). In univariate logistic regression analysis, MetS was significantly associated with AD (odds ratio [OR] 2.71; 95% CI 1.44 to 5.10). In multivariate logistic regression analysis including also apolipoprotein E4 phenotype, education, age, and total cholesterol, MetS was significantly associated with AD (OR 2.46; 95% CI 1.27 to 4.78). If only nondiabetic subjects were included in the multivariate analysis, MetS was still significantly associated with AD (OR 3.26; 95% CI 1.45 to 7.27). CONCLUSION: Metabolic syndrome is associated with Alzheimer disease in elderly subjects.

Plasma ghrelin concentrations are positively associated with carotid artery atherosclerosis in males.

BACKGROUND: Ghrelin, a peptide hormone from stomach, stimulates food intake and decreases fat utilization. Ghrelin binds to growth hormone secretagogue receptor (GHSR). GHSR density has been shown to be upregulated in atherosclerotic lesions, but the relationship between ghrelin concentration and atherosclerosis has not yet been studied. We, therefore, characterized the association between ghrelin concentration and carotid artery intima-media thickness (IMT) in a population-based cohort of 1024 middle-aged (40-60 years) men and women. METHODS: Intima-media thickness and the number of atherosclerotic plaques were determined ultrasonographically. Fasting plasma ghrelin concentrations were analysed using RIA-kit (PhoenixPeptide). RESULTS: There was a positive association between mean IMT and ghrelin concentration in the analysis of males before and after adjustments for the traditional risk factors of atherosclerosis [age, systolic blood pressure, LDL cholesterol, body mass index (BMI), and smoking (ancova, P = 0.004 and P = 0.007, respectively)]. However, no such association was found in females (P = 0.985 and P = 0.915). There was no correlation between ghrelin and CRP concentrations or ghrelin and smoking. CONCLUSION: Ghrelin concentrations and carotid artery atherosclerosis are positively associated in males even after adjustment for the commonly recognized risk factors of atherosclerosis. Experimental and prospective studies are warranted to elucidate the role of ghrelin in atherosclerosis.