Pharmacogenetic association of diabetes-associated genetic risk score with rapid progression of coronary artery calcification following treatment with HMG-CoA-reductase inhibitors -results of the Heinz Nixdorf Recall Study.
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SUBMITTER: Pechlivanis S
PROVIDER: S-EPMC8298241 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND: Atherosclerosis is the primary cause of coronary heart disease (CHD), preceding the onset of cardiovascular disease by decades in most cases. Here we examine the association between single nucleotide polymorphisms (SNPs) integrated on Metabochip and coronary artery calcification (CAC), a valid risk factor for CHD, in an unselected, population-based German cohort. METHODS: The Metabochip is a custom iSELECT array containing >195,000 SNPs that was designed to support large-scale follow-up of putative associations for metabolic and cardiovascular-associated traits. We used generalized linear regression models to explore the impact of Metabochip SNPs on quantitative CAC in 4,329 participants. RESULTS: The 9p21 variant, rs1537373, was most strongly associated (Beta=0.30; 95% confidence interval (CI)=0.21-0.39; p=4.05x10-11) with quantitative CAC. The second strongest association with CAC was with rs9349379 in the phosphatase and actin regulator 1 gene, PHACTR1, (Beta=0.30; 95% CI=0.22-0.40; p=4.67x10-11). Both SNPs remained nominally significant in dichotomized analyses for the presence of any CAC (odds ratiors1537373 (OR)=1.19; 95% CI=1.07-1.31; p=0.001 and ORrs9349379=1.26; 95% CI=1.14-1.40); p=1.5x10-5). Fine mapping of the 9p21 and PHACTR1 gene region revealed several other SNPs that were strongly associated with CAC. CONCLUSION: We demonstrate that SNPs near 9p21 and in PHACTR1 that have previously been shown to be associated with CHD are strongly associated with CAC in the Heinz Nixdorf Recall Study cohort. Our findings suggest that the 9p21 and 6q24 loci might be involved in cardiac outcome via promoting development of atherosclerosis in the coronary arteries.
| S-EPMC3583714 | biostudies-literature
Project description:Study objectivesSeveral studies have assessed the association between midday nap and cardiovascular outcomes and reported heterogenous results. Concern exists that confounding might have distorted these results and contributed to discrepancies among them. This study prospectively examines the association between midday nap habits and the occurrence of coronary artery disease in a non-Mediterranean population.ParticipantsThe baseline examination of 4,123 participants aged 45-75 years.MeasurementsMeasurements included interviews, physical examinations, laboratory tests, and electron beam computed tomography. We studied the influence of midday nap habits on risk of coronary artery disease. We adjusted for several potential confounders including measures of subclinical atherosclerosis-such as coronary calcium score and ankle brachial index-at baseline. Cardiac events during a median follow-up of 8.1 years were defined as nonfatal myocardial infarction and sudden cardiac death.ResultsOverall, 135 of 4,123 subjects (3.3%) either suffered from acute myocardial infarction (81 subjects) or died due to a sudden cardiac death (54 subjects) during follow-up. After adjustment for several confounders including measures of subclinical atherosclerosis, regular long (> 60 min) midday nap was associated with an increased hazard ratio of cardiac events (hazard ratio 2.12, 95% confidence interval 1.11-4.05).ConclusionsAs our detailed confounder analyses showed, confounding is not the sole explanation for this finding. Future research on midday naps should focus on biological mechanisms that may be responsible for increasing the risk of coronary artery disease among subjects taking regular long midday naps.
| S-EPMC3490363 | biostudies-literature
Project description:BACKGROUND:Atherosclerosis is the primary cause of coronary artery disease (CAD). Several observational studies have examined the association of traditional CAD risk factors with the progression of coronary artery calcification (CAC). In our study we investigated the effect of 11 different genetic risk scores associated with CAD and CAD risk factors on the progression of CAC. METHODS AND RESULTS:We included 3097 participants from the Heinz Nixdorf Recall study who had available CAC measurements at baseline (CACb) and at the 5-year follow-up (CAC5y). A weighted genetic risk score for CAD and each of the CAD-associated risk factors was constructed. Multiple regression analyses were applied to i) the difference between the observed log(CAC5y+1) (log(obs)) and expected log(CAC5y+1) (log(exp)) at the 5-year follow-up following the individual's log(CACb+1) percentile for the time between scans (log(obs)-log(exp)) and ii) the 5-year CAC progression, defined as 5*(log(CAC5y+1)-log(CACb+1))/time between the scans, adjusted for age, sex, and log(CACb+1) as well as for risk factors. The median percent deviation from the expected (CAC5y+1) and the 5-year progression of (CAC+1) in our study were 0 (first quartile: Q1; third quartile: Q3: -0.32; 0.48) and 45.4% (0%; 171.0%) respectively. In the age-, sex- and log(CACb+1)-adjusted model, the per-standard deviation (SD) increase in CAD genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (9.7% (95% confidence interval: 5.2%; 14.5%), p = 1.6x10-5) and the 5-year progression of CAC (7.1% (3.0%; 11.4%), p = 0.0005). The CAD genetic risk score explains an additional 0.6% of the observed phenotypic variance for "log(obs)-log(exp)" and 0.4% for 5-year progression of CAC. Additionally, the per-SD increase in the CAC genetic risk score was associated with the percent deviation from the expected (CAC5y+1) (6.2% (1.9%; 10.8%, p = 0.005)) explaining an additional 0.2% of the observed phenotypic variance. However, the per-SD increase in the CAC genetic risk score was not associated with the 5-year progression of CAC (4.4% (0.4%; 8.5%), p = 0.03) after multiple testing. Adjusting for risk factors did not change the results. None of the other genetic risk scores showed an association with the percent deviation from the expected (CAC5y+1) or with the 5-year progression of CAC. CONCLUSIONS:The association of the CAC genetic risk score and the CAD genetic risk score provides evidence that genetic determinants for CAC and CAD influence the progression of CAC.
| S-EPMC7205301 | biostudies-literature
Project description:AimsAir pollution and noise are potential risk factors for subclinical atherosclerosis. Longitudinal analyses, especially on the interplay of these environmental factors, are scarce and inconsistent. Hence we investigated long-term traffic-related exposure to air pollution and noise with the development and progression of thoracic aortic calcification, a marker of subclinical atherosclerosis.MethodsWe used baseline (2000-2003) and follow-up (2006-2008) data from the German Heinz Nixdorf Recall cohort study, including 4814 middle-aged adults. Residence-based air pollution (PM2.5 (aerodynamic diameter ≤ 2.5 µm), PM10, nitrogen dioxide and particle number), and noise was assessed with dispersion models. Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. The presence and extent of thoracic aortic calcification progression were analysed with multiple logistic and linear regression models, respectively, adjusting for age, sex, lifestyle variables, socioeconomic status and respective co-exposure.ResultsWe observed no association in the full study sample (n = 3155, mean age 59.1 (±7.6) years, 52.8% women). While an interquartile range in particle number and night-time noise yielded odds ratios of 1.20 (1.03, 1.40) and 1.21 (1.00, 1.46) for binary thoracic aortic calcification progression, and 0.02 (-0.01, 0.05) and 0.04 (0.00, 0.07) higher growth rates of thoracic aortic calcification in participants with baseline thoracic aortic calcification less than 10, negative findings were observed in those with baseline thoracic aortic calcification of 10 or greater. Results were similar for other pollutants and daytime noise.ConclusionOur study shows no overall associations. Subgroup analyses suggest independent associations of traffic-related air pollution and noise with the development and progression of subclinical atherosclerosis in participants with no or minor thoracic aortic calcification at baseline, in contrast to negative findings in those with advanced calcification.
| S-EPMC7272124 | biostudies-literature
Project description:BackgroundA Genetic risk score for coronary artery disease (CAD) improves the ability of predicting coronary heart disease (CHD). It is unclear whether i) the use of a CAD genetic risk score is superior to the measurement of coronary artery calcification (CAC) for CHD risk assessment and ii) the CHD risk assessment using a CAD genetic risk score differs between men and women.MethodsWe included 4041 participants (age-range: 45-76 years, 1919 men) of the Heinz Nixdorf Recall study without CHD or stroke at baseline. A standardized weighted CAD genetic risk score was constructed using 70 known genetic variants. The risk score was divided into quintiles (Q1-Q5). We specified low (Q1), intermediate (Q2-Q4) and high (Q5) genetic risk groups. Incident CHD was defined as fatal and non-fatal myocardial infarction, stroke and coronary death. The association between the genetic risk score and genetic risk groups with incident CHD was assessed using Cox models to estimate hazard ratios (HR) and 95%-confidence intervals (CI). The models were adjusted by age and sex (Model1), as well as by established CHD risk factors (RF) and CAC (Model2). The analyses were further stratified by sex and controlled for multiple testing.ResultsDuring a median follow-up time of 11.6 ± 3.7 years, 343 participants experienced CHD events (219 men). Per-standard deviation (SD) increase in the genetic risk score was associated with 18% increased risk for incident CHD (Model1: p = 0.002) which did not change after full adjustment (Model2: HR = 1.18 per-SD (p = 0.003)). In Model2 we observed a 60% increased CHD risk in the high (p = 0.009) compared to the low genetic risk group. Stratifying by sex, only men showed statistically significantly higher risk for CHD (Model2: HR = 1.23 per-SD (p = 0.004); intermediate: HR = 1.52 (p = 0.04) and high: HR = 1.88 (p = 0.008)) with no statistically significant risk observed in women.ConclusionOur results suggest that the CAD genetic risk score could be useful for CHD risk prediction, at least in men belonging to the higher genetic risk group, but it does not outbalance the value of CT-based quantification of CAC which works independently on both men and women and allows better risk stratification in both the genders.
| S-EPMC7487988 | biostudies-literature
Project description: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.
| S-EPMC8481271 | biostudies-literature
Project description:BackgroundThe association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events.ObjectiveTo compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcification (CAC).MethodsThe relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication.ResultsMean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19-2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87-1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91-1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87-1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort.ConclusionBaseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves.
| S-EPMC3724227 | biostudies-literature
Project description: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.
| S-EPMC6707579 | biostudies-literature
Project description:IntroductionPoor sleep is a risk factor for adverse health events. For health prevention, it may be helpful to know whether poor sleep or sleep disorders in individuals are associated with sleep problems in their partners or children.MethodsIn the MultiGeneration Study (MGS, conducted from 2013 to 2016), 1237 partners (aged 27 to 90 years) and 1660 adult children (aged 18 to 66 years) of index persons were recruited. Index persons are participants of the Heinz Nixdorf Recall Study, a population-based cohort study in the Ruhr area (study start 1999-2001, 4841 participants aged 45-75 years). We used two analysis populations: one with 1181 index persons whose partners were in MGS, and one with 1083 index persons with at least one adult child in MGS. Sleep characteristics were assessed using questionnaires (including the Pittsburgh Sleep Quality Index). The exposure was the presence of a sleep characteristic of the index subject.ResultsChildren showed the investigated sleep characteristics more often if these were also present in their parent (e.g., RR (relative risk) = 1.28 (95% CI: 1.06-1.55) for poor sleep quality). In partners, strong associations were observed for rising times and napping, but only weak associations for snoring, poor sleep quality and sleep disorders. Snoring of the bed partner is a risk factor for poor sleep (e.g., RR = 1.67 (0.91-3.07) for difficulties falling asleep).ConclusionAggregation is observed for many sleep characteristics in people living in partnerships as well as in parents and their adult children.
| S-EPMC8177478 | biostudies-literature
Project description:Male-pattern baldness (MPB) is characterized by a progressive hair loss from the frontal and vertex scalp that affects about 80% of men at the age of 80 years. Epidemiological studies show positive associations between MPB and coronary heart disease (CHD) and CHD related risk factors such as blood pressure (BP), diabetes mellitus (DM) or elevated blood lipid levels. The results however vary with regard to the pattern of hair loss (i.e. moderate, severe, frontal or vertex). Further, no study has investigated for a shared genetic determinant between MPB and CHD as well as CHD related risk factors. Using the longitudinal data from the population-based Heinz Nixdorf Recall study we aimed to systematically investigate the association between MPB and incident CHD and CHD risk factors on (i) an epidemiological (N = 1,673 males) and (ii) a genetic (N = 1,357 males) level. The prevalence of any baldness in our study population was 88% (mean age ± SD: 64±7.5 years). Compared to men with 'no baldness', in men with any kind of baldness a slightly increased risk for CHD (Hazard ratio [95% confidence interval (95%CI)] = 1.2 [0.8; 1.9]), a slightly higher extend of coronary artery calcification (CAC) (Beta [95%CI] = 0.2 [-0.1; 0.6]), a moderately increased risk for DM (prevalence ratio [95%CI] = 1.4 [0.9; 2.0]) and higher body mass index (BMI) (Beta [95%CI] = 0.6 [0.00003; 1.2]) seem to be indicated in the adjusted model. In contrast, the MPB genetic risk score did not show any association with CHD or CHD risk factors. Taken together, the results of our study suggest a weak association between MPB and a few CHD risk factors (CAC, DM and BMI) but do not point to MPB as a strong surrogate measure for CHD and CHD risk factors in general.
| S-EPMC6863534 | biostudies-literature