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The Apolipoprotein E (APOE) gene polymorphism (rs429358 and rs7412) shows a well-established association with lipid profiles, but its effect on cardiovascular disease is still conflicting. Therefore, we examined the association of different APOE alleles with common carotid artery intima-media thickness (CCA-IMT), carotid plaques, incident myocardial infarction (MI) and stroke. We analyzed data from 3327 participants aged 20–79 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 14.5 years. Linear, logistic, and Cox-regression models were used to assess the associations of the APOE polymorphism with CCA-IMT, carotid plaques, incident MI and stroke, respectively. In our study, the APOE E2 allele was associated with lower CCA-IMT at baseline compared to E3 homozygotes (β: − 0.02 [95% CI − 0.04, − 0.004]). Over the follow-up, 244 MI events and 218 stroke events were observed. APOE E2 and E4 allele were not associated with incident MI (E2 HR: 1.06 [95% CI 0.68, 1.66]; E4 HR: 1.03 [95% CI 0.73, 1.45]) and incident stroke (E2 HR: 0.79 [95% CI 0.48, 1.30]; E4 HR: 0.96 [95% CI 0.66, 1.38]) in any of the models adjusting for potential confounders. However, the positive association between CCA-IMT and incident MI was more pronounced in E2 carriers than E3 homozygotes. Thus, our study suggests that while APOE E2 allele may predispose individuals to lower CCA-IMT, E2 carriers may be more prone to MI than E3 homozygotes as the CCA-IMT increases. APOE E4 allele had no effect on CCA-IMT, plaques, MI or stroke. [ABSTRACT FROM AUTHOR]

Background: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus. Methods: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression. Results: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029). Conclusions: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding. [ABSTRACT FROM AUTHOR]

Background Hepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample. Methods We analyzed data from 3090 women and men, aged 20–81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software. Results The prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF. Conclusions Our findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF. [ABSTRACT FROM AUTHOR]

Aims: To examine the association of different APOE alleles with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) as well as the influence of high-sensitive C-reactive protein (hs-CRP) on these associations.Methods: We analyzed data from 3917 participants aged 20-81 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 10.8 years. Linear and logistic mixed models were performed to test the association of APOE alleles with T2DM and MetS.Results: We observed 393 T2DM and 1411 MetS events at baseline, and 576 T2DM and 1342 MetS events over the follow-up. The E4 carriers had a lower odds of developing T2DM (OR: 0.47 [0.24, 0.94]) than E3 homozygotes even after adjustment for potential confounders. The E2 carriers showed no associations. The inverse association between E4 alleles and T2DM moderately attenuated after adjustment for hs-CRP levels. The lower odds of developing T2DM in E4 carriers was more pronounced in participants without obesity, hypertension or MetS. However, both E2 and E4 carriers had higher odds of developing MetS (E2 OR: 1.45 [1.03, 2.03]; E4 OR: 1.56 [1.17, 2.09]) than E3 homozygotes.Conclusions: While the presence of APOE E4 allele might increase the chance of MetS through its major action on lipids, E4 allele might offer a protection towards T2DM through its influence on inflammation. [ABSTRACT FROM AUTHOR]

Background: The aim of our study was to investigate associations of spleen volume with blood count markers and lipid profile in the general population. Materials & methods: Cross-sectional data from 1,106 individuals aged 30-90 years from the population- based Study of Health in Pomerania (SHIP-START-2) were analyzed. Blood count markers included red blood cell (RBC) counts, hemoglobin, platelet count, and white blood cell (WBC) counts. Lipid profile included total-cholesterol, high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) as well as triglycerides. Linear regression models adjusted for age, sex, body height, and weight were used to associate standardized spleen volume with blood counts and lipid profile markers. Results: Spleen volume was positively associated with RBC (β = 0.05; 95% confidence interval [CI] = 0.03 to 0.08) and hemoglobin (β = 0.05; 95% CI = 0.01 to 0.09) but inversely with platelet count (β = -16.3; 95% CI = -20.5 to -12.1) and WBC (β = -0.25; 95% CI = -0.37 to -0.14). Furthermore, spleen volume showed inverse associations with total cholesterol (β = -0.17; 95% CI = -0.24 to -0.09), HDL-C (β = -0.08; 95% CI = -0.10 to -0.05), and LDL-C (β = -0.12; 95% CI = -0.17 to -0.06). There was no significant association of spleen volume with triglycerides. Conclusion: Our study showed that the spleen volume is associated with markers of the blood count and lipid profile in the general population. [ABSTRACT FROM AUTHOR]

Abstract: Background: The effects of smoking on central aortic pressures and the age-related increase in left ventricular mass (LVM) are largely unknown. We studied the relationship between smoking, arterial distensibility, central aortic pressures and left ventricular mass in two population-based studies. Methods: Data was obtained from two German population-based studies (KORA and SHIP, participants' ages 25–84years). We identified 114 normotensive current smokers and 185 normotensive all-time non-smokers in KORA as well as 400 and 588 such individuals in SHIP. Echocardiographic LVM was obtained at baseline (T0) and follow-up after ten years (T1) in KORA and at follow-up (T1) in SHIP. Additionally, pulse-wave analysis-based central aortic pressure and augmentation index (AIx) were measured at T1 in KORA. Results: Cross-sectional analysis, using KORA T0 and SHIP T1, revealed in both studies a higher covariate-adjusted LVM and left ventricular mass index (LVMI) in smokers as compared with non-smokers. Moreover, in the KORA T1 examination, the smokers demonstrated a more pronounced increase, relative to baseline, of LVM (+13.5%) and LVMI (+13.4%) compared to non-smokers (+8.59% and +8.65%; p=0.036 and 0.042, respectively). Additionally, at KORA T1 smokers had a higher central systolic blood pressure and higher AIx than non-smokers (p=0.012 and p=0.001, respectively). Conclusions: The difference in central aortic pressure due to enhanced and more prolonged wave reflection may explain our finding of a further pronounced increase in left ventricular wall thickness and mass over time in smokers. [Copyright &y& Elsevier]

Objectives: We studied the relationship between changes in body composition and changes in blood pressure levels. Background: The mechanisms underlying the frequently observed progression from pre-hypertension to hypertension are poorly understood. Methods: We examined 1,145 subjects from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. First, we studied individuals pre-hypertensive at baseline who, during 10 years of follow-up, either had normalized blood pressure (PreNorm, n = 48), persistently had pre-hypertension (PrePre, n = 134), or showed progression to hypertension (PreHyp, n = 183). In parallel, we studied predictors for changes in blood pressure category in individuals hypertensive at baseline (n = 429). Results: After 10 years, the PreHyp group was characterized by a marked increase in body weight (+5.71% [95% confidence interval (CI): 4.60% to 6.83%]) that was largely the result of an increase in fat mass (+17.8% [95% CI: 14.5% to 21.0%]). In the PrePre group, both the increases in body weight (+1.95% [95% CI: 0.68% to 3.22%]) and fat mass (+8.09% [95% CI: 4.42% to 11.7%]) were significantly less pronounced than in the PreHyp group (p < 0.001 for both). The PreNorm group showed no significant change in body weight (−1.55% [95% CI: −3.70% to 0.61%]) and fat mass (+0.20% [95% CI: −6.13% to 6.52%], p < 0.05 for both, vs. the PrePre group). Conclusions: After 10 years of follow-up, hypertension developed in 50.1% of individuals with pre-hypertension and only 6.76% went from hypertensive to pre-hypertensive blood pressure levels. An increase in body weight and fat mass was a risk factor for the development of sustained hypertension, whereas a decrease was predictive of a decrease in blood pressure. [Copyright &y& Elsevier]

Objectives: This prospective study evaluated the association of obesity and hypertension with left atrial (LA) volume over 10 years. Background: Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population. Methods: Participants (1,212 men and women, age 25 to 74 years) originated from a sex- and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA ≥35.7 and ≥33.7 ml/m in men and women, respectively. Results: At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up. Conclusions: In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level. [Copyright &y& Elsevier]

We investigated the associations of low handgrip strength (HGS, i.e., a marker of muscular fitness) with liver fat content (LFC) and serum liver enzymes in a population‐based setting. We used data from 2700 participants (51.7% women), aged 21–90 years, from two independent cohorts of the population‐based Study of Health in Pomerania (SHIP‐START‐2 and SHIP‐TREND‐0). Cross‐sectional, multivariable adjusted regression models were performed to examine the associations of HGS with LFC, measured by magnetic resonance imaging and serum liver enzymes. We found significant inverse associations of HGS with both LFC and serum liver enzymes. Specifically, a 10‐kg lower HGS was associated with a 0.59% (95% confidence interval [CI]: 0.24–0.94; p = 0.001) higher LFC, a 0.051 µkatal/L (95% CI: 0.005–0.097; p = 0.031) higher gamma‐glutamyltransferase (GGT) concentration and a 0.010 µkatal/L (95% CI: 0.001–0.020; p = 0.023) higher aspartate aminotransferase (AST) concentration. The adjusted odds‐ratio for prevalent hepatic steatosis (defined by a MRI‐PDFF ≥5.1%) per 10‐kg lower HGS was 1.21 (95% CI: 1.04–1.40; p = 0.014). When considering only obese individuals, those with low HGS had a 1.58% (95% CI: 0.18–2.98; p = 0.027) higher mean LFC and higher chance of prevalent hepatic steatosis (adjusted OR 1.74, 95% CI: 1.15–2.62; p = 0.009) compared to individuals with high HGS. We found similar associations in individuals with overweight, but not in those with normal weight. Lower HGS was strongly associated with both higher LFC and higher serum GGT and AST concentrations. Future studies might clarify whether these findings reflect adverse effects of a sedentary lifestyle or aging on the liver. Highlights: We used magnetic resonance imaging, the most accurate and sensitive noninvasive diagnostic tool for determination of hepatic steatosisLower handgrip strength was strongly associated with both higher liver fat content and higher serum GGT and AST concentrationsEspecially overweight and obese individuals with low handgrip strength had a significant higher risk of prevalent hepatic steatosis [ABSTRACT FROM AUTHOR]

Background and Aims: Non‐alcoholic fatty liver disease (NAFLD) is associated with increased risk for cardiovascular disease. Our study investigates the contribution of NAFLD to changes in cardiac structure and function in a general population. Methods: One thousand ninety‐six adults (49.3% female) from the Study of Health in Pomerania underwent magnetic resonance imaging including cardiac and liver imaging. The presence of NAFLD by proton density fat fraction was related to left cardiac structure and function. Results were adjusted for clinical confounders using multivariable linear regression model. Results: The prevalence for NAFLD was 35.9%. In adjusted multivariable linear regression models, NAFLD was positively associated with higher left ventricular mass index (β = 0.95; 95% confidence interval (CI): 0.45; 1.45), left ventricular concentricity (β = 0.043; 95% CI: 0.031; 0.056), left ventricular end‐diastolic wall thickness (β = 0.29; 95% CI: 0.20; 0.38), left atrial end‐diastolic volume index (β = 0.67; 95% CI: 0.01; 1.32) and inversely associated with left ventricular end‐diastolic volume index (β = −0.78; 95% CI: −1.51; −0.05). When stratified by sex, we only found significant positive associations of NAFLD with left ventricular mass index, left atrial end‐diastolic volume index, left ventricular cardiac output and an inverse association with global longitudinal strain in women. In contrast, men had an inverse association with left ventricular end‐diastolic volume index and left ventricular stroke volume. Higher liver fat content was stronger associated with higher left ventricular mass index, left ventricular concentricity and left ventricular end‐diastolic wall thickness. Conclusion: NAFLD is associated with cardiac remodelling in the general population showing sex specific patterns in cardiac structure and function. [ABSTRACT FROM AUTHOR]

Adipokines and cardiorespiratory fitness (CRF) are associated with the (patho)physiology of cardiometabolic diseases. Whether CRF and adipokines are related is unclear. We investigated associations of CRF with leptin, adiponectin, chemerin, resistin and vaspin. Data from the population-based Study of Health in Pomerania was used (n=1,479; median age 49 years; 51% women). Cardiopulmonary exercise testing was used to measure CRF. Circulating adipokine concentrations were measured by enzyme-linked immunosorbent assay. The association between CRF and adipokines was assessed using multivariable sex-specific quantile regression models. Higher maximum oxygen uptake was significantly associated with lower leptin (men:−0.11 ng/ml; 95%-confidence interval [CI]:−0.18 to−0.03 ng/ml; p<0.005; women:−0.17 ng/ml; 95%-CI:−0.33 to−0.02 ng/ml; p<0.05) and chemerin (men:−0.26 ng/ml; 95%-CI:−0.52 to−0.01 ng/ml; p<0.05; women:−0.41 ng/ml; 95%-CI:−0.82 to−0.01 ng/ml; p<0.05) as well as higher adiponectin concentrations (men: 0.06 µg/ml; 95%-CI: 0.02 to 0.11 µg/ml; p<0.05; women: 0.03 µg/ml; 95%-CI:−0.05 to 0.10 µg/ml; p=0.48). We found that CRF was inversely associated with leptin and chemerin in both sexes and positively associated with adiponectin only in men. [ABSTRACT FROM AUTHOR]

Background: Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes. Methods: Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models. Results: In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m2.7 (1.80 to 0.57; p < 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m2.7/ml (0.06 to 0.17; p < 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p < 0.001) higher left ventricular concentricity. Conclusions: Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart. [ABSTRACT FROM AUTHOR]

Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (β per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p < 0.001); diastolic blood pressure: 2.29 (p < 0.001) in HCHS). Systolic blood pressure correlated with declining diastolic function (β per SD for E/e′: 0.29, p < 0.001 in HCHS) and diastolic blood pressure with declining systolic function (β per SD for LVEF, in %: − 0.15; p = 0.041 in HCHS) in all cohorts. Pending further validation, our results from three independent German population samples suggest differential effects of systolic versus diastolic blood pressure on left ventricular structure and function. [ABSTRACT FROM AUTHOR]

Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (β per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p < 0.001); diastolic blood pressure: 2.29 (p < 0.001) in HCHS). Systolic blood pressure correlated with declining diastolic function (β per SD for E/e′: 0.29, p < 0.001 in HCHS) and diastolic blood pressure with declining systolic function (β per SD for LVEF, in %: − 0.15; p = 0.041 in HCHS) in all cohorts. Pending further validation, our results from three independent German population samples suggest differential effects of systolic versus diastolic blood pressure on left ventricular structure and function. [ABSTRACT FROM AUTHOR]

Purpose: The aim is to investigate the associations of the mother's socioeconomic and lifestyle factors and life satisfaction with the delivery of a small for gestational age (SGA) infant. Methods: Data from 4598 participants of the population-based birth cohort study Survey of Neonates in Pomerania (SniP) including comprehensive information on pregnancies, mothers, and their offspring in Western Pomerania, Germany were used in this study. The associations were analyzed using linear and logistic regression models. Results: After logistic regression analysis adjusted for height of the mother, women who delivered SGA infants, had lower education (p < 0.01) and smoked more frequently during pregnancy (p < 0.01) compared with mothers of adequate for gestational age (AGA) neonates. A mother with less than 10 years of education and one who continued smoking during pregnancy had an odds ratio (OR) of 2.23 [95% confidence interval (CI) = 1.44 to 3.46] and 2.68 (95% CI = 2.06–3.49) of having an SGA infant, respectively. There was no association between the employment of the mother (p = 0.28), the monthly income (p = 0.09), the family status (p = 0.80), the number of friendships outside the household that the mother would not wish to relinquish (p = 0.47), the number of people that she could rely on in case of an emergency (p = 0.75), or alcohol consumption prior to (p = 0.14) or during the pregnancy (p = 0.99) with SGA. Finally, women who delivered SGA infants were more frequently dissatisfied with their employment (p = 0.03) and financial status (p < 0.01). Conclusions: Women who delivered SGA infants had more associated socioeconomic and lifestyle risk factors and were more frequently dissatisfied with their life conditions than mothers of AGA neonates. [ABSTRACT FROM AUTHOR]

Background: We investigated the association between low cardiorespiratory fitness and liver fat content (LFC) in the general population. Materials and Methods: We evaluated data from 2151 adults (51.1% women) from two population‐based cohorts of the Study of Health in Pomerania (SHIP‐2 and SHIP‐TREND‐0). We analysed the cross‐sectional associations of peak oxygen uptake (VO2peak) with LFC, assessed by magnetic resonance imaging proton density fat fraction, as well as serum gamma‐glutamyltransferase (GGT) and aminotransferase concentrations by multivariable regression models. Results: We observed significant inverse associations of VO2peak with LFC and serum GGT, but not with serum aminotransferase levels. Specifically, a 1 L/min lower VO2peak was associated with a 1.09% (95% confidence interval [CI]: 0.45‐1.73; P =.002) higher LFC and a 0.18 μkatal/L (95% CI: 0.09‐0.26; P <.001) higher GGT levels. The adjusted odds ratio (OR) for the risk of prevalent hepatic steatosis (HS) by a 1 L/min decrease in VO2peak was 1.61 (95% CI: 1.22‐2.13; P =.001). Compared to subjects with high VO2peak, obese and overweight individuals with low VO2peak had 1.78% (95% CI: 0.32‐3.25; P =.017) and 0.94% (95% CI: 0.15‐1.74; P =.021) higher mean LFC, respectively. Compared to those with high VO2peak, low VO2peak was independently associated with a higher risk of prevalent HS in the obese (adjusted‐OR 2.29, 95% CI=1.48‐3.56; P <.001) and overweight (adjusted OR 1.57, 95% CI=1.16‐2.14; P =.04) groups. Conclusions: Lower VO2peak was significantly associated with greater LFC and higher serum GGT levels in a population‐based cohort of adult individuals. Our results suggest that low VO2peak might be a risk factor for HS. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate the association of hepatic steatosis derived from quantitative ultrasound and magnetic resonance imaging (MRI) with prediabetes in a large population-based study conducted in Northeast Germany. Hepatic steatosis was assessed through transabdominal ultrasound and quantitative MRI. For analysis we included 1622 subjects with MRI who participated in an oral glucose tolerance test and reported no known type 2 diabetes mellitus (T2DM). We classified participants as proposed by the American Diabetes Association: isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT), and undiagnosed T2DM. Regression models were adjusted for age, sex body mass index and alcohol consumption. We observed positive associations of hepatic steatosis with glycated hemoglobin, fasting glucose and insulin, 2-h glucose and insulin, as well as homeostasis model assessment-insulin resistance index. Similarly, individuals having hepatic steatosis as defined by MRI had a higher relative risk ratio (RR) to be in the prediabetes groups i-IFG (RR = 1.6; 95% confidence interval (CI) 1.2; 2.2), i-IGT (RR = 3.3, 95% CI 2.0; 5.6) and IFG + IGT (RR = 2.5, 95% CI 1.6; 3.9) or to have undiagnosed T2DM (RR = 4.8, 95% CI 2.6; 9.0). All associations were attenuated when defining hepatic steatosis by ultrasound. Hepatic steatosis is associated with prediabetes and undiagnosed T2DM in the general population. Quantitative liver MRI revealed stronger associations with prediabetes and undiagnosed T2DM compared to ultrasound, which indicates the higher sensitivity and specificity of MRI to determine hepatic steatosis. [ABSTRACT FROM AUTHOR]

A simple equation established by Cordova & Cordova (LDL-COR) was developed to provide an improved estimation of LDL-cholesterol in a large Brazilian laboratory database. We evaluated this new equation in a general population cohort in Pomerania, north-eastern Germany (SHIP Study) compared to other existing formulas (Anandaraja, Teerakanchana, Chen, Hattori, Martin, Friedewald and Ahmadi), and its power in the prediction of death by atherosclerosis related events as the primary outcome. Analysis was conducted on a cohort of 4075 individuals considering age, gender, use of lipid lowering therapy and associated co-morbidities such as diabetes, hepatic, kidney and thyroid disease. LDL-COR values had a lower standard deviation compared to the previously published equations: 0.92 versus 1.02, 1.02, 1.03, 1.04, 1.09, 1.10 and 1.74 mmol/L, respectively. All of the factors known to affect the results obtained by the Friedewald's equation (LDL-FW), except fibrate use, were associated with the difference between LDL-COR and LDL-FW (p < .01), with TSH being borderline (p = .06). LDL-COR determined a higher hazard ratio (1.23 versus 1.12, 1.19, 1.21, 1.19, 1.21 and 1.19) for cardiovascular disease related mortality, incident stroke or myocardial infarction compared to the other evaluated formulas, except for Ahmadi's (1.24), and the same adjusted predictive power considering all confounding factors. The proposed simple equation was demonstrated to be suitable for a more precise LDL-c estimation in the studied population. Since LDL-c is a parameter frequently requested by medical laboratories in clinical routine, and will probably remain so, precise methods for its estimation are needed when direct measurement is not available. [ABSTRACT FROM AUTHOR]

Aims: Compare performances of diabetes risk scores and glycated hemoglobin (HbA1c) to estimate the risk of incident type 2 diabetes mellitus (T2DM) in Northeast Germany.Methods: We studied 2916 subjects (20 to 81years) from the Study of Health in Pomerania (SHIP) in a 5-year follow-up period. Diabetes risk scores included the Cooperative Health Research in the Region of Augsburg (KORA) base model, the Danish diabetes risk score and the Data from the Epidemiological Study on the Insulin Resistance syndrome (D.E.S.I.R) clinical risk score. We assessed the performance of each of the diabetes risk scores and the HbA1c for 5-year risk of T2DM by the area under the receiver-operating characteristic curve (AUC) and calibration plots.Results: In SHIP, the incidence of T2DM was 5.4% (n=157) in the 5-year follow-up period. Diabetes risk scores and HbA1c achieved AUCs ranging from 0.76 for the D.E.S.I.R. clinical risk score to 0.82 for the KORA base model. For diabetes risk scores, the discriminative ability was lower for the age group 55 to 74years. For HbA1c, the discriminative ability also decreased for the group 55 to 74years while it was stable in the age group 30 to 64years old.Conclusions: All diabetes risk scores and the HbA1c showed a good prediction for the risk of T2DM in SHIP. Which model or biomarker should be used is driven by its context of use, e.g. the practicability, implementation of interventions and availability of measurement. [ABSTRACT FROM AUTHOR]

Background: Hepatic steatosis confers an increased risk of metabolic and cardiovascular disease and higher health services use. Associations of the single nucleotide polymorphisms (SNP) PNPLA3 rs738409 and TM6SF2 rs58542926 with hepatic steatosis have recently been established. This study investigates the association between rs738409 and rs58542926 with health services utilization in a general population.Methods: Data of 3759 participants from Study of Health in Pomerania (SHIP), a population-based study in Germany, were obtained. The annual number of outpatient visits, hospitalization and length of hospital stay was regressed on rs738409 and rs58542926 and adjusted for socio-economic factors, lifestyle habits, clinical factors, and health status.Results: Minor allele homozygous subjects of rs738409 had an increased odds of hospitalization as compared to major allele homozygous subjects (odds ratio [OR] 1.51; 95% confidence interval [CI], 1.02 to 2.15). Heterozygous subjects did not differ from major allele homozygous subjects with respect to their odds of hospitalization. The three genotype groups of rs738409 were similar with respect to the number of outpatient visits and inpatient days. Minor allele homozygous and heterozygous subjects of rs58542926 had higher outpatient utilization (+53.04% and +67.56%, p < 0.05, respectively) and inpatient days than major allele homozygous subjects.Conclusions: After adjustment for several confounding factors, PNPLA3 rs738409 and TM6SF2 rs58542926 were associated with the number of outpatient visits, hospitalization, and inpatient days. Further studies are warranted to replicate our findings and to evaluate whether genetic data can be used to identify subjects with excess health services utilization. [ABSTRACT FROM AUTHOR]

Objective Periodontitis is considered to promote atherosclerosis and cardiovascular diseases through increased low-grade systemic inflammation. However, there is no information on the long-term impact of periodontitis on systemic inflammation from cohort studies. Thus, this study aims to assess the impact of periodontitis on systemic inflammation (fibrinogen and white blood cells (WBC)) in a population-based longitudinal survey in north-eastern Germany. Methods The study sample comprised 2622 subjects from the Study of Health in Pomerania with complete 5- and 11-year follow-ups. Periodontitis was assessed by probing depth and clinical attachment level. Multilevel regression analyses were applied to evaluate associations between periodontitis measures and i) fibrinogen/WBC count using 11-year follow-up data and ii) respective z-scores of fibrinogen/WBC count using 5- and 11-year follow-up data. We adjusted for common cardiovascular risk factors and stratified analyses by abdominal obesity (P for interaction <0.10). Results In lean subjects, beta-coefficients of mean probing depth were B = 0.13 (0.08-0.019; P < 0.001) for fibrinogen and B = 0.50 (0.37-0.64; P < 0.001) for WBC count using 11-year follow-up data only. For lean subjects, models using z-scores confirmed that increased mean probing depths were associated with increased fibrinogen z-scores (B = 0.14 (0.09-0.18; P < 0.001)) and increased WBC z-scores (B = 0.16 (0.11-0.20; P < 0.001)). Consistent results were found for mean clinical attachment levels. For abdominally obese subjects, relations between periodontitis measures and levels of inflammation markers were less pronounced or non-significant. Conclusion Modified by abdominal obesity, periodontitis affected systemic inflammation in a significant dose-dependent manner. Results contribute to the discussion on how periodontitis is linked to atherosclerosis and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Summary Objective Prolactin (PRL) is involved in immune regulation and may contribute to an atherogenic phenotype. Previous results on the association of PRL with inflammatory biomarkers have been conflicting and limited by small patient studies. Therefore, we used data from a large population-based sample to assess the cross-sectional associations between serum PRL concentration and high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6 (IL-6), and white blood cell (WBC) count. Design and Population From the population-based Study of Health in Pomerania (SHIP), a total of 3744 subjects were available for the present analyses. Methods and Measurements PRL and inflammatory biomarkers were measured. Linear and logistic regression models adjusted for age, sex, body-mass-index, total cholesterol and glucose were analysed. Results Multivariable linear regression models revealed a positive association of PRL with WBC. Multivariable logistic regression analyses showed a significant association of PRL with increased IL-6 in non-smokers [highest vs lowest quintile: odds ratio 1·69 (95% confidence interval 1·10-2·58), P = 0·02] and smokers [OR 2·06 (95%-CI 1·10-3·89), P = 0·02]. Similar results were found for WBC in non-smokers [highest vs lowest quintile: OR 2·09 (95%-CI 1·21-3·61), P = 0·01)] but not in smokers. Linear and logistic regression analyses revealed no significant associations of PRL with hsCRP or fibrinogen. Conclusions Serum PRL concentrations are associated with inflammatory biomarkers including IL-6 and WBC, but not hsCRP or fibrinogen. The suggested role of PRL in inflammation needs further investigation in future prospective studies. [ABSTRACT FROM AUTHOR]

Objectives: This prospective study evaluated the association of obesity and hypertension with left atrial (LA) volume over 10 years. Background: Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population. Methods: Participants (1,212 men and women, age 25 to 74 years) originated from a sex- and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA > or =35.7 and > or =33.7 ml/m in men and women, respectively. Results: At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up. Conclusions: In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level. [ABSTRACT FROM AUTHOR]

Aims: To assess the role of serum ferritin and transferrin with prevalent and incident type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) and whether these associations are independent of inflammatory markers and hepatic enzymes.Methods: We analyzed data from 3,232 participants aged 20-81 years of the population-based Study of Health in Pomerania (SHIP) from Northeast Germany with a median follow-up time of 10.6 years. Logistic and Cox regression analyses were performed.Results: Serum ferritin concentrations were associated with a higher prevalence of T2DM (total population OR: 1.16 [95% CI: 1.07, 1.26]; men OR: 1.18 [95% CI: 1.08, 1.30) and MetS (total population OR: 1.27 [95% CI: 1.16, 1.38]; men OR: 1.26 [95% CI: 1.15, 1.38]) in the total population and men independently of inflammatory markers and hepatic enzymes. In longitudinal analyses, baseline ferritin concentrations were associated with a higher risk of incident T2DM in women (HR: 1.38 [95% CI: 1.10, 1.71]), but not in men or in the total population and also with a higher risk of incident MetS (HR: 1.09 [95% CI: 1.01, 1.17]) in the total population. These longitudinal associations attenuated considerably after adjustment for hepatic enzymes but not inflammatory markers. Transferrin was not associated with any of the outcomes.Conclusions: Our results suggest a link between ferritin and T2DM and MetS, which might be partially explained by hepatic dysfunction. [ABSTRACT FROM AUTHOR]

Background: Previous studies found regional differences in the prevalence and incidence of type 2 diabetes between Northeast and South of Germany. The aim of this study was to investigate if regional variations are also present for macrovascular disease in people with type 2 diabetes and in the general population. A further aim was to investigate if traditional risk factors of macrovascular complications can explain these regional variations.Methods: Data of persons aged 30-79 from two regional population-based studies, SHIP-TREND (Northeast Germany, 2008-2012, n = 2539) and KORA-F4 (South Germany, 2006-2008, n = 2932), were analysed. Macrovascular disease was defined by self-reported previous myocardial infarction, stroke or coronary angiography. Multivariable logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for prevalence of macrovascular disease in persons with type 2 diabetes and in the general population.Results: The prevalence of macrovascular disease in persons with type 2 diabetes and in the general population was considerably higher in the Northeast (SHIP-TREND: 32.8 and 12.0%) than in the South of Germany (KORA-F4: 24.9 and 8.8%), respectively. The odds of macrovascular disease in persons with type 2 diabetes was 1.66 (95% CI: 1.11-2.49) in the Northeast in comparison to the South after adjustment for sex, age, body mass index, hypertension, hyperlipidemia and smoking. In the general population, SHIP-TREND participants also had a significantly increased odds of macrovascular disease compared to KORA-F4 participants (OR = 1.63, 95% CI: 1.33-2.00). After excluding coronary angiography (myocardial infarction or stroke only), the ORs for region decreased in all models, but the difference between SHIP-TREND and KORA-F4 participants was still significant in the age- and sex-adjusted model for the general population (OR = 1.34, 95% CI: 1.01-1.78).Conclusions: This study provides an indication for regional differences in macrovascular disease, which is not explained by traditional risk factors. Further examinations of other risk factors, such as regional deprivation or geographical variations in medical care services are needed. [ABSTRACT FROM AUTHOR]