scholarly journals Bayesian variable selection with a pleiotropic loss function in Mendelian randomization

2019 ◽  
Author(s):  
Apostolos Gkatzionis ◽  
Stephen Burgess ◽  
David V Conti ◽  
Paul J Newcombe
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Variable Selection ◽  
Diastolic Blood Pressure ◽  
Loss Function ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Bayesian Variable Selection

AbstractMendelian randomization is the use of genetic variants as instruments to assess the existence of a causal relationship between a risk factor and an outcome. A Mendelian randomization analysis requires a set of genetic variants that are strongly associated with the risk factor and only associated with the outcome through their effect on the risk factor. We describe a novel variable selection algorithm for Mendelian randomization that can identify sets of genetic variants which are suitable in both these respects. Our algorithm is applicable in the context of two-sample summary-data Mendelian randomization and employs a recently proposed theoretical extension of the traditional Bayesian statistics framework, including a loss function to penalize genetic variants that exhibit pleiotropic effects. The algorithm offers robust inference through the use of model averaging, as we illustrate by running it on a range of simulation scenarios and comparing it against established pleiotropy-robust Mendelian randomization methods. In a real data application, we study the effect of systolic and diastolic blood pressure on the risk of suffering from coronary heart disease. Based on a recent large-scale GWAS for blood pressure, we use 395 genetic variants for systolic and 391 variants for diastolic blood pressure. Both traits are shown to have significant risk-increasing effects on coronary heart disease risk.

Abstract 031: Diastolic Blood Pressure, Coronary Artery Calcium, and Cardiac Outcomes in the Multi-ethnic Study of Atherosclerosis

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
John W McEvoy ◽  
Faisal Rahman ◽  
Mahmoud Al Rifai ◽  
Michael Blaha ◽  
Khurram Nasir ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Artery ◽  
Confidence Interval ◽  
Diastolic Blood Pressure ◽  
Coronary Artery Calcium ◽  
J Curve ◽  
Increased Risk ◽  
All Cause Mortality

Diastolic blood pressure (BP) has a J-curve relationship with coronary heart disease and death. Because this association is thought to reflect reduced coronary perfusion at low diastolic BP, our objective was to test whether the J-curve is most pronounced among persons with coronary artery calcium. Among 6,811 participants from the Multi-Ethnic Study of Atherosclerosis, we used Cox models to examine if diastolic BP category is associated with coronary heart disease events, stroke, and mortality. Analyses were conducted in the sample overall and after stratification by coronary artery calcium score. In multivariable-adjusted analyses, compared with diastolic BP of 80 to 89 mmHg (reference), persons with diastolic BP <60 mmHg had increased risk of coronary heart disease events (HR 1.69 [95% confidence interval 1.02-2.79]) and all-cause mortality (HR 1.48 [95% confidence interval 1.10-2.00]), but not stroke. After stratification, associations of diastolic BP <60 mmHg with events were present only among participants with coronary artery calcium >0. Diastolic BP <60 mmHg was not associated with events when coronary artery calcium was zero. We also found no interaction in the association between low diastolic BP and events based on race. In conclusion, diastolic blood pressure <60 mmHg was associated with increased risk of coronary heart disease events and all-cause mortality in the sample overall, but this association appeared strongest among individuals with elevated CAC; suggesting that added caution may be needed when pursuing intensive BP treatment targets among persons with subclinical atherosclerosis.

scholarly journals High Blood Pressure and Cardiovascular Disease

Hypertension ◽  
2020 ◽  
Vol 75 (2) ◽  
pp. 285-292 ◽  
Author(s):  
Flávio D. Fuchs ◽  
Paul K. Whelton
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Cohort Studies ◽  
High Blood Pressure ◽  
Population Distribution ◽  
Meta Analysis ◽  
Age Related

Fragmented investigation has masked the overall picture for causes of cardiovascular disease (CVD). Among the risk factors for CVD, high blood pressure (BP) is associated with the strongest evidence for causation and it has a high prevalence of exposure. Biologically, normal levels of BP are considerably lower than what has typically been characterized as normal in research and clinical practice. We propose that CVD is primarily caused by a right-sided shift in the population distribution of BP. Our view that BP is the predominant risk factor for CVD is based on conceptual postulates that have been tested in observational investigations and clinical trials. Large cohort studies have demonstrated that high BP is an important risk factor for heart failure, atrial fibrillation, chronic kidney disease, heart valve diseases, aortic syndromes, and dementia, in addition to coronary heart disease and stroke. In multivariate modeling, the presumed attributable risk of high BP for stroke and coronary heart disease has increased steadily with progressive use of lower values for normal BP. Meta-analysis of BP-lowering randomized controlled trials has demonstrated a benefit which is almost identical to that predicted from BP risk relationships in cohort studies. Prevention of age-related increases in BP would, in large part, reduce the vascular consequences usually attributed to aging, and together with intensive treatment of established hypertension would eliminate a large proportion of the population burden of BP-related CVD.

Systolic versus diastolic blood pressure and risk of coronary heart disease

1971 ◽  
Vol 27 (4) ◽  
pp. 335-346 ◽  
Author(s):  
William B. Kannel ◽  
Tavia Gordon ◽  
Melvin J. Schwartz
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Diastolic Blood Pressure

scholarly journals MR-Clust: Clustering of genetic variants in Mendelian randomization with similar causal estimates

2019 ◽  
Author(s):  
Christopher N Foley ◽  
Paul D W Kirk ◽  
Stephen Burgess
Keyword(s):  
Blood Pressure ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Causal Effect ◽  
Coronary Artery Disease Risk ◽  
Artery Disease

AbstractMotivationMendelian randomization is an epidemiological technique that uses genetic variants as instrumental variables to estimate the causal effect of a risk factor on an outcome. We consider a scenario in which causal estimates based on each variant in turn differ more strongly than expected by chance alone, but the variants can be divided into distinct clusters, such that all variants in the cluster have similar causal estimates. This scenario is likely to occur when there are several distinct causal mechanisms by which a risk factor influences an outcome with different magnitudes of causal effect. We have developed an algorithm MR-Clust that finds such clusters of variants, and so can identify variants that reflect distinct causal mechanisms. Two features of our clustering algorithm are that it accounts for uncertainty in the causal estimates, and it includes ‘null’ and ‘junk’ clusters, to provide protection against the detection of spurious clusters.ResultsOur algorithm correctly detected the number of clusters in a simulation analysis, outperforming the popular Mclust method. In an applied example considering the effect of blood pressure on coronary artery disease risk, the method detected four clusters of genetic variants. A hypothesis-free search suggested that variants in the cluster with a negative effect of blood pressure on coronary artery disease risk were more strongly related to trunk fat percentage and other adiposity measures than variants not in this cluster.Availability and ImplementationMR-Clust can be downloaded from https://github.com/cnfoley/[email protected] or [email protected] InformationSupplementary Material is included in the submission.

scholarly journals Relationship Between Blood Pressure and Incident Cardiovascular Disease

Hypertension ◽  
2021 ◽  
Author(s):  
Rainer Malik ◽  
Marios K. Georgakis ◽  
Marijana Vujkovic ◽  
Scott M. Damrauer ◽  
Paul Elliott ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Diastolic Blood Pressure ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Hazard Ratio ◽  
European Ancestry ◽  
Artery Disease

Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a history of CVD or antihypertensive medication use. There was no evidence favoring nonlinear relationships of genetically proxied systolic and diastolic blood pressure with the cardiovascular outcomes over linear relationships. For every 10-mm Hg increase in genetically proxied systolic blood pressure, risk of incident CVD increased by 49% (hazard ratio, 1.49 [95% CI, 1.38–1.61]), with similar estimates obtained for coronary artery disease (hazard ratio, 1.50 [95% CI, 1.38–1.63]) and stroke (hazard ratio, 1.44 [95% CI, 1.22–1.70]). Genetically proxied blood pressure had a similar relationship with CVD in men and women. These findings provide evidence to support that even for individuals who do not have elevated blood pressure, public health interventions achieving persistent blood pressure reduction will be of considerable benefit in the primary prevention of CVD.

Abstract P448: Exploring Socioeconomic Inequalities In Coronary Heart Disease Prevention

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
R Ahmed ◽  
Martin O'Flaherty ◽  
N Hawkins ◽  
J Lucy ◽  
Simon Capewell
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
Primary Prevention ◽  
Systolic Blood Pressure ◽  
Population Based ◽  
Policy Model ◽  
English Population ◽  
Asymptomatic Individuals

Background: Between 2000 and 2007, coronary heart disease (CHD) mortality rates in England plummeted by one third. An important part of this substantial CHD mortality decline was achieved through reductions in major cardiovascular risk factors (primary prevention). However, the relative contributions from medications and from population-wide changes remains unclear, particularly the effects on health inequalities. Methods: Using a previously validated policy model, the fall in CHD mortality in England was analysed. The contributions from risk factor declines in asymptomatic individuals through medications and through population-wide changes were quantified. Data were stratified using the Index of Multiple Deprivation (IMD). Model outputs were quantified as deaths prevented or postponed (DPPs). Results: Between 2000 and 2007, approximately 21,900 fewer CHD deaths were attributable to risk factor declines in systolic blood pressure and cholesterol in the English population. Some 7,100 of these 21,900 fewer deaths (DPPs) were attributed to medications (32%) and approximately 14,800 DPPs were attributed to secular changes in asymptomatic individuals (68%). Substantial declines in systolic blood pressure were responsible for approximately 14,300 fewer deaths. This comprised approximately 12,500 DPPs attributable to population-wide changes and some 1,800 DPPs attributable to hypertension medications. The hypertension medications resulted in approximately 350 fewer deaths in the most affluent quintile compared with 270 DPP in the most deprived. In contrast, the population-wide (secular) falls in blood pressure resulted in approximately 2400 fewer deaths in the most deprived quintile compared with only 1900 DPPs in the most affluent. Cholesterol falls resulted in approximately 7,700 fewer deaths. This comprised some 5,300 fewer deaths attributable to statin medications and approximately 2,400 fewer deaths attributable to population-wide changes (mostly diet). Statin medications prevented more deaths in the most affluent quintile (1050 DPPs) compared with the most deprived (770 DPPs). Population-wide changes in cholesterol prevented substantially more deaths in the most deprived quintile (820 DPPs) compared with the most affluent (260 DPPs). Conclusions: Population-based declines in blood pressure and cholesterol resulted in much greater reductions in CHD deaths than did primary prevention medications. Mortality falls were greatest in the most deprived quintiles, mainly reflecting their bigger initial burden of disease. Future CHD prevention policies should prioritise healthier diets ahead of medications.

PREVALENCE OF HYPERTENSION AND TREATMENT OUTCOME IN TERTIARY CARE

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Dr. Rajendra Prasad Gupta ◽  
Dr. Satish Chandra Arya
Keyword(s):  
Blood Pressure ◽  
Coronary Heart Disease ◽  
Risk Factor ◽  
Heart Disease ◽  
High Blood Pressure ◽  
Resistant Hypertension ◽  
Tertiary Care ◽  
Hypertensive Crisis ◽  
Normal Weight ◽  
Age Group

INTRODUCTION: High blood pressure (BP) is ranked as the third most important risk factor for attributable burden of disease in south Asia. Raised blood pressure is a major risk factor for chronic heart disease, stroke, and coronary heart disease. WHO rates hypertension as one of the most important causes of premature death worldwide[i].  In India 57% of all stroke deaths and 24% of all coronary heart disease (CHD) deaths are due to hypertension. Other than coronary heart disease and stroke, complications include peripheral vascular disease, heart failure, renal impairment, retinal hemorrhage, and visual impairment. MATERIAL AND METHODS: Study population was adult patients who had been receiving anti-hypertensive treatment at hospital for at least 6 months. Interviews were conducted with all the participants and the questionnaires were filled. Demographic and anthropometric data were obtained for the patient who includes height and weight, BMI (Body Mass Index), personal medical history was obtained, and diagnosis of hypertension and other co-morbid conditions were recorded. RESULTS: A total of 200 patients were included in this study were observed and traced up to 6 month period of the study. 200 patients were included in the study of which 117 (58.50%) were male and 83 (41.50%) were female. Mean age of male patients was 52 ± 18.29 while in female it was 53 ± 17.88. We have divided our patients into four groups in <20 years only one male patient (0.85%) was having hypertension. In 20 – 39 years age group 16 (13.67%) male and 8 (9.63%) female were observed. In 40 to 59 age group 47 (35.04%) male and 31 (37.35%) female were observed. In >60 age group there were 53(45.30%) male and 44 (53.01%) female were observed. Maximum number of cases were observed in the >60 age group in both the sexes. 46 male (39.32%) and 35(42.17%) female had history of hypertension with Less than 5 years. while 71 (60.68%) male and 48 (57.83%) female had hypertension for more than five years. Out of 117 male 13 (11.11%) were normal weight, 85 (72.65%) were overweight and 19 (16.24%) were obese. In female 4 (4.82%) were normal weight, 69 (85.13%) were overweight and 10 (12.50%) were obese. Hypertension was most prevalent in overweight group in both the sexes. Diabetes was observed in 71 (60.68%) male and 56 (67.47%) female. 46 (39.32%) male and 27(32.53%) of female had myocardial infarction.   Before start of the study 68 (58.12%) had controlled blood pressure, 42 (35.90%) had uncontrolled BP, Hypertensive crisis was seen in 5 (4.27%) patients and Resistant hypertension was seen in 2 (1.71%) cases. After study period 58 (49.57%) had controlled blood pressure, 22 (18.80%) had uncontrolled BP, Hypertensive crisis was seen in 2 (1.71%) patients and Resistant hypertension was seen in 1 (0.85%) case. CONCLUSION:  Chronic uncontrolled high blood pressure which can be reduced by proper management, counselling and lifestyle modification. Prevalence of hypertension in males was slightly higher than female counterparts .Control of hypertension was more in female patients. Also patient assessment should be improved in order to increase the identification and management of hypertension KEYWORDS: Hypertension, Diabetes, coronary heart disease (CHD), management.

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