scholarly journals Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease

Heart ◽  
2019 ◽  
Vol 105 (13) ◽  
pp. 975-981 ◽  
Author(s):  
Ralph Kwame Akyea ◽  
Joe Kai ◽  
Nadeem Qureshi ◽  
Barbara Iyen ◽  
Stephen F Weng
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Competing Risks ◽  
Density Lipoprotein ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
National Guidelines ◽  
Increased Risk ◽  
Future Risk

ObjectiveTo assess low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of cardiovascular disease (CVD).MethodsProspective cohort study of 165 411 primary care patients, from the UK Clinical Practice Research Datalink, who were free of CVD before statin initiation, and had at least one pre-treatment LDL-C within 12 months before, and one post-treatment LDL-C within 24 months after, statin initiation. Based on current national guidelines, <40% reduction in baseline LDL-C within 24 months was classified as a sub-optimal statin response. Cox proportional regression and competing-risks survival regression models were used to determine adjusted hazard ratios (HRs) and sub-HRs for incident CVD outcomes for LDL-C response to statins.Results84 609 (51.2%) patients had a sub-optimal LDL-C response to initiated statin therapy within 24 months. During 1 077 299 person-years of follow-up (median follow-up 6.2 years), there were 22 798 CVD events (12 142 in sub-optimal responders and 10 656 in optimal responders). In sub-optimal responders, compared with optimal responders, the HR for incident CVD was 1.17 (95% CI 1.13 to 1.20) and 1.22 (95% CI 1.19 to 1.25) after adjusting for age and baseline untreated LDL-C. Considering competing risks resulted in lower but similar sub-HRs for both unadjusted (1.13, 95% CI 1.10 to 1.16) and adjusted (1.19, 95% CI 1.16 to 1.23) cumulative incidence function of CVD.ConclusionsOptimal lowering of LDL-C is not achieved within 2 years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future CVD.

scholarly journals Impact of changes to national guidelines on hypertension related workload

2020 ◽  
pp. bjgp21X714281
Author(s):  
Sarah Lay-Flurrie ◽  
James Sheppard ◽  
Richard J Stevens ◽  
Christian Mallen ◽  
Carl Heneghan ◽  
...  
Keyword(s):  
Interrupted Time Series ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Interrupted Time Series Analysis ◽  
National Guidelines ◽  
Nice Guidelines ◽  
Face To Face ◽  
General Practices ◽  
The Impact

Background: In 2011, National Institute for Health and Care Excellence (NICE) guidelines recommended the routine use of out-of-office blood pressure (BP) monitoring for the diagnosis of hypertension. These changes were predicted to reduce unnecessary treatment costs and workload associated with misdiagnosis. Aim: To assess the impact of guideline change on rates of hypertension-related consultation in general practice. Design and Setting: Cohort study in adults registered with English general practices contributing to the Clinical Practice Research Datalink between 1/4/2006 and 31/3/2017. Method: The primary outcome was the rate of face-to-face, telephone and visit consultations related to hypertension with a GP or nurse. Age and sex standardized rates were analysed using interrupted time-series analysis. Results: In 3,937,191 adults (median follow-up = 4.2 years) there were 12,253,836 hypertension related consultations. The rate of hypertension related consultation was 71.0 per 100 person-years (95% CI 67.8 to 74.2) in April 2006, which remained flat prior to 2011. The introduction of the NICE hypertension guideline in 2011 was associated with a change in yearly trend (change in trend = -3.60 per 100 person-years, 95% CI -5.12 to -2.09). The rate of consultation subsequently decreased to 59.2 per 100 person-years (95% CI 56.5 to 61.8) in March 2017. These changes occurred around the time of diagnosis and persisted when accounting for wider trends in all consultations. Conclusion: Hypertension-related workload has declined in the last decade, in association with guideline changes. This is due to changes in workload at the time of diagnosis, rather than reductions in misdiagnosis.

scholarly journals P203 Oral glucocorticoid use is associated with hypertension in patients with RA

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Ruth E Costello ◽  
Meghna Jani ◽  
Belay B Yimer ◽  
William G Dixon
Keyword(s):  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Incident Hypertension ◽  
Increased Risk ◽  
Risk Attribution ◽  
Predominantly Female ◽  
Oral Glucocorticoids

Abstract Background Oral glucocorticoids (GC) are frequently prescribed to patients with rheumatoid arthritis (RA), however GC use is associated with several potential side effects. Hypertension is cited as a possible side effect, but few studies have specifically investigated GC-associated hypertension in patients with RA with conflicting results. The aim of this study was to determine whether GCs were associated with an increased risk of incident hypertension in a cohort of patients with RA. Methods A retrospective cohort of patients with incident RA and no hypertension at RA diagnosis were identified from UK primary care electronic health records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use and dose, categorised as: no use, &gt;0-4.9 mg/day, 5-7.4 mg/day, 7.5-14.9 mg/day, ≥15mg/day. A 3-month risk attribution model was used where patients continued to remain at risk for 3 months after the end of prescriptions. Hypertension was identified if a patient had either: 1) 2 consecutive systolic blood pressure (BP) measurements &gt;140mmHg within a year, 2) 2 consecutive diastolic BP measurements &gt;90mmHg within a year or 3) antihypertensive prescriptions on at least two occasions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards (PH) regression models were fitted to determine if there was an association between GC use and hypertension. Results There were 17,760 patients with incident RA and no hypertension. The cohort had a mean age of 56.3 ± 12.7 years and were predominantly female (68%). 7,421 (42%) were prescribed GCs during follow-up. There were 6,243 cases of incident hypertension. The Cox PH model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio: 1.17 (95% CI 1.10 to 1.24)). When categorised by dose, only doses above 7.5mg were significantly associated with hypertension (Table 1). Conclusion In this large cohort of patients with RA and without hypertension, recent GC use was associated with incident hypertension. Doses ≥7.5mg were associated with hypertension while the association with lower doses was inconclusive. Clinicians need to consider cardiovascular risk when prescribing GCs and ensure BP is regularly monitored. Disclosures R.E. Costello None. M. Jani None. B.B. Yimer None. W.G. Dixon None.

scholarly journals Low Density Lipoprotein Cholesterol Is Associated With Increased Risk of Cardiovascular Disease in Participants Over 70 Years Old: A Prospective Cohort Study

2021 ◽  
Author(s):  
xin Su ◽  
Deqiang Zheng ◽  
Meiping Wang ◽  
Yingting Zuo ◽  
Jing Wen ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Heart Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Unmeasured Confounding ◽  
Increased Risk

Abstract BackgroundPrevious studies, in which the data were collected about half a century ago, suggested that elevated low density lipoprotein cholesterol (LDL-C) is not associated with increased risk of cardiovascular disease (CVD) in patients over 70 years old. However, what is the relationship between LDL-C and CVD risk in a contemporary population aged over 70 years has not been well examined in China.MethodsThe China Health and Retirement Longitudinal Study (CHARLS) is an ongoing nationally representative study. In this analysis, participants of CHARLS who did not taking statins and did not have heart disease and stroke at 2011 were include and were followed up to 2018. The outcome of this analysis was occurrence of CVD at follow up, which include heart disease and stroke. Cox regression was used to assess the harmful effect of LDL-C on CVD occurrence. We calculated e-values to quantify the effect of unmeasured confounding on our results.ResultsOf the 9,631 participants, 15.2% (N=1,463) were aged over 70 years and 52.5% (N=5,060) were female. During the 7 years follow-up, 1,437 participants had a first CVD attack. Risk of CVD occurrence increased 8% with each 10 mg/mL elevation in LDL-C in whole participants (adjusted HR, 1.08; 95% CI, 1.06-1.10) and age groups of ≥70 years, 60-69years and <60 years. Similar results were observed in subgroup analyses, in which participants were stratified by sex, hypertension, diabetes and chronic kidney disease. According to the restricted cubic spline, we noted a U-shaped relationship between LDL-C and risk of CVD occurrence in group over 70 years old, however, we further found that in the left side of U-shape curve, LDL-C was not associated with occurrence of CVD and its attribution to CVD occurrence was only 2.1%, which indicated that lower level of LDL-C could not increase the risk of CVD occurrence as it was demonstrated by a U-shape association. E-value analysis suggested robustness to unmeasured confounding.ConclusionsIn contemporary society of China, elevated the level of LDL-C also increased the risk of CVD in participants over 70 years old as in the relatively younger participants. These results should strengthen guideline recommendations for the use of lipid lowering therapies in those elderly.

scholarly journals Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Bishnu M. Singh ◽  
Hari K. Lamichhane ◽  
Sanjay S. Srivatsa ◽  
Prabhat Adhikari ◽  
Bikash J. Kshetri ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Events ◽  
Statin Therapy ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Cochrane Library ◽  
Atherosclerotic Cardiovascular Disease ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
High Range

AbstractObjectiveThe objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods: We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results: Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR=0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR=0.78, 95% CI: 0.63 to 0.96), major coronary events (RR=0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR=0.71, 95% CI: 0.62 to 0.82), revascularizations (RR=0.65, 95% CI: 0.57 to 0.74), angina (RR=0.76, 95% CI: 0.63 to 0.92) and hospitalization for cardiovascular causes (RR=0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion: Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C near-optimal to the borderline high range without prior atherosclerotic cardiovascular disease.

scholarly journals Infectious Disease Burden and the Risk of Alzheimer’s Disease: A Population-Based Study

2021 ◽  
pp. 1-10
Author(s):  
Antonios Douros ◽  
Christina Santella ◽  
Sophie Dell’Aniello ◽  
Laurent Azoulay ◽  
Christel Renoux ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Burden ◽  
Population Based ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Cumulative Number ◽  
Increased Risk

Background: Previous studies suggested a link between various infectious pathogens and the development of Alzheimer’s disease (AD), posing the question whether infectious disease could present a novel modifiable risk factor. Objective: To assess whether infectious disease burden due to clinically apparent infections is associated with an increased risk of AD. Methods: We conducted a population-based nested case-control study using the United Kingdom Clinical Practice Research Datalink. We included all dementia-free subjects ≥50 years of age enrolling in the database between January 1988 and December 2017. Each case of AD identified during follow-up was matched with up to 40 controls. Conditional logistic regression estimated adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of AD associated with ≥1 infection diagnosed >  2 years before the index date compared with no infection during the study period. We further stratified by time since first infection and cumulative number of infections. Results: The cohort included overall 4,262,092 individuals (mean age at cohort entry 60.4 years; 52% female). During a median follow-up of 10.5 years, 40,455 cases of AD were matched to 1,610,502 controls. Compared with having no burden of infectious disease, having a burden of infectious disease was associated with an increase in the risk of AD (OR, 1.05; 95% CI, 1.02 to 1.08). The risk increased with longer time since first infection, peaking after 12–30 years (OR, 1.11; 95% CI, 1.05–1.17). The risk did not increase with cumulative number of infections. Conclusion: The overall risk of AD associated with infectious disease burden was small but increased gradually with longer time since first infection.

Assessing the relationship between serum potassium variability and the risk of hyperkalaemia and adverse clinical outcomes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P McEwan ◽  
K Badora ◽  
D Sugrue ◽  
G James ◽  
M Hurst ◽  
...  
Keyword(s):  
Serum Potassium ◽  
Index Date ◽  
Adverse Outcomes ◽  
Practice Research ◽  
Major Adverse Cardiovascular Events ◽  
Clinical Practice Research Datalink ◽  
Funding Source ◽  
Private Company ◽  
Increased Risk

Abstract Background Serum potassium (SK+) is a vital electrolyte, which level is maintained by adjusting renal K+ excretion. Variability in SK+ has been linked to increased risk of mortality and other adverse clinical events in patients in intensive care and/or receiving haemodialysis, prompting a similar investigation in cardiovascular patients. Purpose To examine the effect of SK+ variability on all-cause mortality (ACM) and the incidence of major adverse cardiovascular events (MACE), comprising arrhythmia, [subsequent records of] HF, myocardial infarction, or stroke, in patients with heart failure (HF) or resistant hypertension (RHTN). Methods Patients aged ≥18 years with HF or RHTN were identified from the UK Clinical Practice Research Datalink (CPRD, primary care data) and linked Hospital Episode Statistics (HES, secondary care data). HF and RHTN were defined through READ codes recorded during the study period (2008-June 2018) or the five-year look-back period (2003–2007). Index date was set to 1st January 2008 or initial diagnosis; whichever occurred later. Mean SK+ and variability of measurements (quantified as standard deviation [SD] and each patient categorised as low or highly variable based on the median SD of the cohort), and crude incidence rates of ACM and MACE were estimated over a follow-up period from index date to event or end of follow-up (death, loss to follow-up or end of study, whichever was earlier). Results The eligible population included 317,135 RHTN patients and 84,210 HF patients with a mean follow-up of 6.37 (SD 3.06) and 5.01 (SD 3.20) years, respectively. In both cohorts, higher mean SK+ ≥5.0 mmol/L was associated with increased rates of ACM and MACE relative to a mean SK+ of 3.5–5 mmol/L (Table 1). High SK+ variability was associated with increased incidence of adverse outcomes, with rates consistently higher in the high SK+ variability group compared to low-variability patients with the same diagnosis and mean SK+ category (Table 1); all comparisons were statistically significant except for ACM in HF patients with mean SK+ ≥5 mmol/L. Conclusion Independently of mean SK+, increased variability in SK+ levels was associated with an increased rate of mortality and MACE in patients with RHTN or HF. Careful SK+ monitoring and management to maintain SK+ concentrations may improve the outcomes of patients with RHTN and HF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Familial hypercholesterolemia and response to statin therapy according to LDLR genetic background

2005 ◽  
Vol 43 (8) ◽  
Author(s):  
Despoina M. Choumerianou ◽  
George V. Z. Dedoussis
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Receptor Gene ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Increased Risk ◽  
Density Lipoprotein Receptor

AbstractFamilial hypercholesterolemia is an autosomal dominant disease defined at the molecular level mainly by the presence of mutations in the low-density lipoprotein receptor gene and is characterized by elevated low-density lipoprotein cholesterol, tendon xanthomas and increased risk of early cardiovascular disease. The type of mutation in the low-density lipoprotein receptor gene has been associated with different phenotype expression and response to statins. Several studies have been undertaken to assess the efficacy of statins and evaluate the influence of mutations on the response to treatment with statins. Not all patients respond to statin therapy with a reduction in cardiovascular disease. In this review paper, we will discuss the results available to date that correlate the low-density lipoprotein receptor genotype to the response to statins, and the interest in developing diagnostic systems which will allow identification of patients at increased risk of adverse drug reactions or patients in which a therapeutic effect is lacking.

scholarly journals Role of Statins in the Primary Prevention of Atherosclerotic Cardiovascular Disease and Mortality in the Population with Mean Cholesterol in the Near-Optimal to Borderline High Range: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bishnu M. Singh ◽  
Hari K. Lamichhane ◽  
Sanjay S. Srivatsa ◽  
Prabhat Adhikari ◽  
Bikash J. Kshetri ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Adverse Events ◽  
Statin Therapy ◽  
Meta Analysis ◽  
Density Lipoprotein ◽  
Cochrane Library ◽  
Atherosclerotic Cardiovascular Disease ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
High Range

Objective. The objective of this meta-analysis was to analyze the benefits and harms of treating the population with statins in those having mean low-density lipoprotein cholesterol (LDL-C) in the near-optimal (100 to 129 mg/dl) to borderline high (130 to 159 mg/dl) range and free of cardiovascular disease (CVD). Methods. We searched PubMed, PubMed Central, Cochrane Library, and Google Scholar databases for randomized controlled trials (RCTs) published between 1994 and July 2020. We included RCTs with greater than 90% of participants free of CVD. Two reviewers independently screened the articles using the Covidence software, assessed the methodological quality using the risk of bias 2 tool, and analyzed the data using the RevMan 5.4 software. Results. Eleven trials were included. Statin therapy was associated with a decreased risk of myocardial infarction (RR = 0.56, 95% CI: 0.47 to 0.67), major cerebrovascular events (RR = 0.78, 95% CI: 0.63 to 0.96), major coronary events (RR = 0.67, 95% CI: 0.57 to 0.80), composite cardiovascular outcome (RR = 0.71, 95% CI: 0.62 to 0.82), revascularizations (RR = 0.65, 95% CI: 0.57 to 0.74), angina (RR = 0.76, 95% CI: 0.63 to 0.92), and hospitalization for cardiovascular causes (RR = 0.74, 95% CI: 0.64 to 0.86). There was no benefit associated with statin therapy for cardiovascular mortality and coronary heart disease mortality. All-cause mortality benefit with statin therapy was seen in the population with diabetes and increased risk of CVD. Statin therapy was associated with no significant increased risk of myalgia, creatine kinase elevation, rhabdomyolysis, myopathy, incidence of any cancer, incidence of diabetes, withdrawal of the drug due to adverse events, serious adverse events, fatal cancer, and liver enzyme abnormalities. Conclusion. Statin therapy was associated with a reduced risk of cardiovascular disease and procedures without increased risk of harm in populations with mean LDL-C in the near-optimal to the borderline high range and without prior atherosclerotic cardiovascular disease.

Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Disease

2020 ◽  
Vol 26 (43) ◽  
pp. 5617-5627
Author(s):  
Mirjana Stojković ◽  
Miloš Žarković
Keyword(s):  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiac Electrophysiology ◽  
Vascular System ◽  
Density Lipoprotein ◽  
Thyroid Stimulating Hormone ◽  
Normal Limits ◽  
Developing Heart ◽  
Treatment Indications ◽  
Increased Risk

The prevalence of subclinical hypothyroidism (SH) is 3-10%. The prevalence of subclinical hyperthyroidism (SHr) is 0.7-9.7%. Thyroid hormones affect cardiac electrophysiology, contractility, and vasculature. SH is associated with an increased risk of coronary heart disease (CHD), especially in subjects under 65. SHr seems to be associated with a slightly increased risk of CHD and an increase in CHD-related mortality. Both SH and SHr carry an increased risk of developing heart failure (HF), especially in those under 65. Both SH and SHr are associated with worse prognoses in patients with existing HF. SH is probably not associated with atrial fibrillation (AF). SHr, low normal thyroid-stimulating hormone (TSH) and high normal free thyroxine (FT4) are all associated with the increased risk of AF. An association between endothelial dysfunction and SH seems to exist. Data regarding the influence of SHr on the peripheral vascular system are conflicting. SH is a risk factor for stroke in subjects under 65. SHr does not increase the risk of stroke. Both SH and SHr have an unfavourable effect on cardiovascular disease (CVD) and all-cause mortality. There is a U-shaped curve of mortality in relation to TSH concentrations. A major factor that modifies the relation between subclinical thyroid disease (SCTD) and mortality is age. SH increases blood pressure (BP). SHr has no significant effect on BP. Lipids are increased in patients with SH. In SHr, high-density lipoprotein cholesterol and lipoprotein( a) are increased. SCTD should be treated when TSH is over 10 mU/l or under 0.1 mU/l. Treatment indications are less clear when TSH is between normal limits and 0.1 or 10 mU/L. The current state of knowledge supports the understanding of SCTD’s role as a risk factor for CVD development. Age is a significant confounding factor, probably due to age-associated changes in the TSH reference levels.

scholarly journals Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women

2021 ◽  
pp. jech-2020-214358
Author(s):  
Pekka Martikainen ◽  
Kaarina Korhonen ◽  
Aline Jelenkovic ◽  
Hannu Lahtinen ◽  
Aki Havulinna ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Risk Score ◽  
Density Lipoprotein ◽  
Population Based ◽  
Polygenic Risk Score ◽  
Genome Wide ◽  
Increased Risk ◽  
Region Of Residence

BackgroundGenetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events.MethodsThe data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers.ResultsAllowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education.ConclusionsPRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

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