Katharina Lau

Cohort Profile: The Study of Health in Pomerania

Henry Volzke, y Dietrich Alte,1y Carsten Oliver Schmidt, Dorte Radke, Roberto Lorbeer, Nele Friedrich, Nicole Aumann, Katharina Lau, Michael Piontek, Gabriele Born, Christoph Havemann, Till Ittermann, Sabine Schipf, Robin Haring, Sebastian E Baumeister, Henri Wallaschofski, Matthias Nauck, Stephanie Frick, Andreas Arnold, Michael Junger, Julia Mayerle, Matthias Kraft, Markus M Lerch, Marcus Dorr, Thorsten Reffelmann, Klaus Empen, Stephan B Felix, Anne Obst, Beate Koch, Sven Glaser, Ralf Ewert, Ingo Fietze, Thomas Penzel, Martina Doren, Wolfgang Rathmann, Johannes Haerting, Mario Hannemann, Jurgen Ropcke, Ulf Schminke, Clemens Jurgens, Frank Tost, Rainer Rettig, Jan A Kors, Saskia Ungerer, Katrin Hegenscheid, Jens-Peter Kuhn, Julia Kuhn, Norbert Hosten, Ralf Puls, Jorg Henke, Oliver Gloger, Alexander Teumer, Georg Homuth, Uwe Volker, Christian Schwahn, Birte Holtfreter, Ines Polzer, Thomas Kohlmann, Hans J Grabe, Dieter Rosskopf, Heyo K Kroemer, Thomas Kocher, Reiner Biffar,17,y Ulrich John20y and Wolfgang Hoffmann1y

Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in caucasians.

A recent genome‐wide study revealed an association between variation in the PNPLA3 gene and liver fat content. In addition, the PNPLA3 single‐nucleotide polymorphism rs738409 (M148I) was reported to be associated with advanced alcoholic liver disease in alcohol‐dependent individuals of Mestizo descent. We therefore evaluated the impact of rs738409 on the manifestation of alcoholic liver disease in two independent German cohorts. Genotype and allele frequencies of rs738409 (M148I) were determined in 1,043 alcoholic patients with or without alcoholic liver injury and in 376 at‐risk drinkers from a population‐based cohort. Relative to alcoholic patients without liver damage (n = 439), rs738409 genotype GG was strongly overrepresented in patients with alcoholic liver cirrhosis (n = 210; OR 2.79; Pgenotype = 1.2 × 10−5; Pallelic = 1.6 × 10−6) and in alcoholic patients without cirrhosis but with elevated alanine aminotransferase levels (n = 219; OR 2.33; Pgenotype = 0.0085; Pallelic = 0.0042). The latter, biochemically defined association was confirmed in an independent population‐based cohort of at‐risk drinkers with a median alcohol intake of 300 g/week (OR 4.75; Pgenotype = 0.040; Pallelic = 0.022), and for aspartate aminotransferase (AST) levels. Frequencies of allele PNPLA3 rs738409(G) in individuals with steatosis and normal alanine aminotransferase (ALT) and AST levels were lower than in alcoholics without steatosis and normal ALT/AST (Pcombined = 0.03). The population attributable risk of cirrhosis in alcoholic carriers of allele PNPLA3 rs738409(G) was estimated at 26.6%. Conclusion: Genotype PNPLA3 rs738409(GG) is associated with alcoholic liver cirrhosis and elevated aminotransferase levels in alcoholic Caucasians. (HEPATOLOGY 2011)

Low total testosterone is associated with increased risk of incident type 2 diabetes mellitus in men: results from the Study of Health in Pomerania (SHIP)

Objective. There is increasing evidence suggesting that low total testosterone concentration is associated with incident type 2 diabetes mellitus (T2DM) in men. The aim of this study was to evaluate the association between total testosterone and incident T2DM in a large population-based cohort. Methods. Of 2117 men at baseline, 1589 were followed up 5 years later. Low total testosterone concentration at baseline determined by <10th percentile (10-year age-strata) were used as a risk factor for incident T2DM at follow-up. To evaluate for potential non-response bias, drop out weights were used in sensitivity analysis. Results. From 1339 men eligible for analyses, 68 (5.1%) developed T2DM. Men with low total testosterone concentration had an increased risk of developing T2DM (odds ratio [OR] 3.4, 95% CI 1.9–6.1), even after adjustment for age, waist circumference and smoking, OR 3.0; (95% CI 1.6–5.7). Recalculated weighted models revealed almost identical estimates indicating no relevant non-response bias. Discussion. Our prospective findings suggest that low total testosterone concentration is associated with incident T2DM in men and might represent a biomarker that might causally be involved in the risk of T2DM. This underlines the importance of measuring total testosterone in men as the predominant male sex hormone.

The association between fatty liver disease and blood pressure in a population-based prospective longitudinal study.

Objective The aim of the present study was to investigate the association of fatty liver disease (FLD) with blood pressure (BP) and hypertension in a general population sample with prospective 5-year follow-up examinations. Design and methods We used data from the Study of Health in Pomerania, conducted in the northeastern part of Germany. The study population comprised 3191 individuals aged 20–79 years. FLD was defined as the presence of a hyperechogenic pattern of the liver and increased serum alanine transferase (ALT) levels. Results Multivariable analyses revealed that FLD was associated with increased DBP and hypertension at baseline and with increased SBP and hypertension at follow-up. In individuals with FLD, the chance of hypertension at baseline and follow-up was three-fold higher [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.3–6.2 and OR 3.1; 95% CI 1.7–5.8, respectively] compared to individuals without FLD. In the subgroup of individuals not receiving antihypertensive medication, FLD was associated with all BP-related variables at baseline and follow-up. Analyses further suggest that these associations were independent of alcohol consumption and further confounders. Conclusion FLD defined by liver hyperechogenity and increased ALT levels is associated with progression of BP over time and incident hypertension. In individuals with FLD, BP should be checked regularly and interventions addressing behavioural risk factors for FLD and hypertension should be initiated if necessary. Ultrasound should be implemented as a method to detect FLD in individuals with increased ALT levels in routine medical care.

Association between alcohol consumption and carotid intima–media thickness in a healthy population: data of the STRATEGY study (Stress, Atherosclerosis and ECG Study)

Background/Objectives:Epidemiological evidence suggests a protective effect of moderate alcohol consumption on cardiovascular events. However, studies assessing the association between alcohol intake and intima–media thickness (IMT) as a marker of subclinical atherosclerosis have provided inconsistent results. The aim of this analysis of the Stress Atherosclerosis and ECG Study (STRATEGY study) was to investigate the relation between alcohol intake and IMT in a selectively healthy population.Subjects/Methods:In a cross-sectional study, laboratory values, anthropometric data, nutrition habits and physical activity were assessed in 106 men and 107 women, evenly distributed between 30 and 70 years. Carotid IMT was determined by B-mode ultrasonography according to the standardized protocol of the Study of Health in Pomerania.Results:In men, a significant positive correlation between daily alcohol consumption and IMT was observed (P<0.0001), whereas in women the positive correlation was not significant. The type of beverage consumed did not affect this finding. The mean IMT was significantly higher in men with an alcohol intake above the upper limit of 20 g/day than in men with an alcohol intake <20 g/day (P<0.001). According to a stepwise linear regression model adjusted for age, conventional risk factors, nutrition and physical activity, the IMT increases by 0.0253 mm per 21.4 g/day intake of alcohol in men (P<0.05).Conclusions:The STRATEGY study revealed a positive association between alcohol consumption and carotid IMT in healthy men aged 30–70 years. This relationship remained significant after adjustment for nutrition, physical activity, anthropometry and conventional cardiovascular risk factors.

The association between fatty liver disease and blood pressure in a population-based cohort study.

I n our recently published paper in the Journal of Hypertension [1] we investigated the cross-sectional and longitudinal association of fatty liver disease (FLD) with blood pressure (BP) and hypertension in a general population cohort. Furthermore, we analyzed the specific contribution of alcohol consumption to this association. We drew four main conclusions: first, FLD as evidenced by liver hyperechogenicity and increased serum alanine aminotransferase (ALT) levels is associated with BP-related variables and hypertension at baseline. Second, FLD predicts the progression of BP and the development of hypertension after 5 years. Third, alcohol consumption has a minor contribution to the association of FLD with BP-related variables and hypertension. Fourth, the findings emphasize the necessity to implement liver

Reported Beverage Consumed and Alcohol-Related Diseases among Male Hospital Inpatients with Problem Drinking

AIMS The aim of this study was to examine if problem drinkers have varying risks of having alcohol-related diseases according to their reported beverage consumed. METHODS In a cross-sectional study all consecutive inpatients aged 18- 64 years from four general hospitals of one catchment area were systematically screened for alcohol use. A total of 1011 men with problem drinking were used for this study. Routine treatment diagnoses for all participants were provided by hospital physicians and were classified into three categories according to their alcohol-attributable fractions (AAF; AAF = 0; AAF < 1; AAF = 1). RESULTS According to their reported beverage consumed, 53.0% of the participants were identified as exclusively beer drinkers, 14.1% exclusively spirits drinkers, 26.0% mixed beer and spirits drinkers and 6.9% individuals drinking wine exclusively or in combination with one or two other beverages (mixed wine drinkers). Compared to spirits drinkers and controlling for possible confounders (i.e. alcohol-associated characteristics, demographic variables), multinomial regressions revealed that beer drinkers, mixed beer and spirits drinkers, and mixed wine drinkers had lower odds of having diseases with AAF = 1 than spirits drinkers (e.g. for AAF = 1: beer versus spirits drinkers: OR = 0.42, CI: 0.25-0.72). Beer drinkers and mixed wine drinkers also had lower odds of having diseases with AAF < 1 than spirits drinkers (e.g. mixed wine versus spirits drinkers: OR = 0.36, CI: 0.18-0.72). CONCLUSIONS These data suggest an association between the reported beverage consumed and alcohol-related diseases. Among hospitalized problem drinkers, spirits drinkers had the greatest risk of having diseases with AAF < 1 and with AAF = 1.