Association between socioeconomic position and cystatin C in the Heinz Nixdorf Recall Study.

Social inequalities in health and disease are well studied. Less information is available on inequalities in biomarker levels indicating subclinical stages of disease such as cystatin C, an early diagnostic marker of renal dysfunction and predictor for cardiovascular disease. We evaluated the relationship between cystatin C, socioeconomic position (SEP) and established cardiovascular risk factors in a population-based study. In 4475 men and women aged 45-75 years participating in the baseline examination of the Heinz Nixdorf Recall Study cystatin C was measured from serum samples with a nephelometric assay. SEP was assessed by education and household income. Linear regression models were used to analyse the association between SEP and cystatin C as well as the impact of cardiovascular risk factors (i.e., body mass index, blood pressure, blood glucose, diabetes mellitus, blood lipids, C-reactive protein, smoking) on this association. After adjustment for age and sex cystatin C decreased by 0.019 mg/l (95% confidence interval (CI) - 0.030 to - 0.008) per five years of education. While using a categorical education variable cystatin C presented 0.039 mg/l (95% CI 0.017-0.061) higher in men and women in the lowest educational category (≤ 10 years of education) compared to the highest category (≥ 18 years). Concerning income, cystatin C decreased by 0.014 mg/l (95% CI - 0.021 to - 0.006) per 1000 € after adjustment for age and sex. For men and women in the lowest income quartile cystatin C was 0.024 mg/l (95% CI 0.009-0.038) higher compared to the highest income quartile. After adjusting for established cardiovascular risk factors the observed associations were substantially diminished. Social inequalities seem to play a role in subclinical stages of renal dysfunction, which are also related to development of cardiovascular disease. Adjustment for traditional cardiovascular risk factors showed that these risk factors largely explain the association between SEP and cystatin C.

Socioeconomic position is associated with N-terminal pro-brain natriuretic peptide (NT-proBNP)-Results of the population-based Heinz Nixdorf Recall study.

OBJECTIVES: N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. METHODS: Baseline data of 4598 participants aged 45-75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. RESULTS: With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. CONCLUSIONS: In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

A genetic sum score of effect alleles associated with serum lipid concentrations interacts with educational attainment.

High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) levels are influenced by both genes and the environment. The aim was to investigate whether education and income as indicators of socioeconomic position (SEP) interact with lipid-increasing genetic effect allele scores (GES) in a population-based cohort. Using baseline data of 4516 study participants, age- and sex-adjusted linear regression models were fitted to investigate associations between GES and lipids stratified by SEP as well as including GES×SEP interaction terms. In the highest education group compared to the lowest stronger effects per GES standard deviation were observed for HDL-C (2.96 mg/dl [95%-CI: 2.19, 3.83] vs. 2.45 mg/dl [95%-CI: 1.12, 3.72]), LDL-C (6.57 mg/dl [95%-CI: 4.73, 8.37] vs. 2.66 mg/dl [95%-CI: -0.50, 5.76]) and TC (8.06 mg/dl [95%-CI: 6.14, 9.98] vs. 4.37 mg/dl [95%-CI: 0.94, 7.80]). Using the highest education group as reference, interaction terms showed indication of GES by low education interaction for LDL-C (ßGES×Education: -3.87; 95%-CI: -7.47, -0.32), which was slightly attenuated after controlling for GESLDL-C×Diabetes interaction (ßGES×Education: -3.42; 95%-CI: -6.98, 0.18). The present study showed stronger genetic effects on LDL-C in higher SEP groups and gave indication for a GESLDL-C×Education interaction, demonstrating the relevance of SEP for the expression of genetic health risks.

Interaction of Alzheimer's Disease-Associated Genetic Risk with Indicators of Socioeconomic Position on Mild Cognitive Impairment in the Heinz Nixdorf Recall Study.

BACKGROUND: The apolipoprotein E (APOE) ɛ4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI. OBJECTIVE: To investigate whether APOEɛ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort. METHODS: Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOEɛ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex. RESULTS: Indication for interaction on the additive scale was found between APOEɛ4 and low education on MCI (RERI: 0.52 [95% confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOEɛ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed. CONCLUSION: Results indicate that low education may have an impact on APOEɛ4 expression on MCI, especially among women.

A genetic sum score of risk alleles associated with body mass index interacts with socioeconomic position in the Heinz Nixdorf Recall Study.

Body mass index (BMI) is influenced by genetic, behavioral and environmental factors, while interactions between genetic and socioeconomic factors have been suggested. Aim of the study was to investigate whether socioeconomic position (SEP) interacts with a BMI-related genetic sum score (GRSBMI) to affect BMI in a population-based cohort. SEP-related health behaviors and a GRS associated with educational attainment (GRSEdu) were included in the analysis to explore potential interactions underlying the GRSBMIxSEP effect. Baseline information on SEP indicators (education, income), BMI, smoking, physical activity, alcohol consumption and genetic risk factors were available for 4,493 participants of the Heinz Nixdorf Recall Study. Interaction analysis was based on linear regression as well as on stratified analyses. In SEP-stratified analyses, the highest genetic effects were observed in the lowest educational group with a 0.24 kg/m2 higher BMI (95%CI: 0.16; 0.31) and in the lowest income quartile with a 0.14 kg/m2 higher BMI (95%CI: 0.09; 0.18) per additional risk allele. Indication for a GRSBMIxSEP interaction was observed for education (ßGRSbmixeducation = -0.02 [95%CI:-0.03; -0.01]) and income (ßGRSbmixincome = -0.05 [95%CI: -0.08; -0.02]). When adjusting for interactions with the GRSEdu and SEP-related health behaviors, effect size estimates of the GRSBMIxSEP interaction remained virtually unchanged. Results gave indication for an interaction of BMI-related genetic risk factors with SEP indicators, showing substantially stronger genetic effects in low SEP groups. This supports the hypothesis that expression of genetic risks is higher in socioeconomically disadvantaged environments. No indication was observed that the GRSBMIxSEP interaction was affected by other SEP-related factors included in the analysis.

Socioeconomic Status Interacts with the Genetic Effect of a Chromosome 9p21.3 Common Variant to Influence Coronary Artery Calcification and Incident Coronary Events in the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary Calcium, and Lifestyle).

BACKGROUND: Genetic variants of a locus within the chromosome 9p21.3 region are consistently associated with coronary artery disease and coronary artery calcification (CAC). The aim of this study was to examine whether a 9p21.3 common variant interacts with socioeconomic status (SES) to influence CAC and incident coronary events in a population-based cohort. METHODS AND RESULTS: 9p21.3 single nucleotide polymorphism rs2891168 was genotyped in 4116 participants of the Heinz Nixdorf Recall study. SES indicators (education and income) and CAC were assessed at baseline. Incident coronary events were ascertained over a median follow-up of 9.3 years. Multiple regression models were fitted to estimate genetic effects on loge(CAC+1) and incident coronary events. Genetic effects were highest in the lower income tertile with a 53.1% (95% confidence interval, 30.6%-79.6%; P=1.8×10 -7) increase in CAC and a hazard ratio of 1.44 (95% confidence interval, 1.01-2.07; P=0.049) for incident coronary events per additional risk allele. After including genotype×SES interaction terms in the regression models, genotype×income interactions were observed for CAC (exp[ßg×income]=0.85 [95% confidence interval, 0.74-0.98; Pg×income=0.02] per 1000€/mo increase and additional risk allele) and for incident coronary events (hazard ratiog×income=0.69 [95% confidence interval, 0.48-0.98; Pg×income=0.04] per 1000€/mo increase and additional risk allele). No interaction was observed using education as SES indicator. CONCLUSIONS: A 9p21.3 common variant seems to interact with SES to influence CAC and incident coronary events in a population-based cohort. This supports the hypothesis that better material, psychosocial, and lifestyle conditions enable higher SES groups to reduce the expression of their genetic susceptibility to coronary artery disease.