scholarly journals Causal Associations of Urate With Cardiovascular Risk Factors: Two-Sample Mendelian Randomization

2021 ◽  
Vol 12 ◽  
Author(s):  
Thitiya Lukkunaprasit ◽  
Sasivimol Rattanasiri ◽  
Boonsong Ongphiphadhanakul ◽  
Gareth J. McKay ◽  
John Attia ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Instrumental Variables ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Effects ◽  
Sensitivity Analyses ◽  
Cardiac Risk Factor

BackgroundMendelian Randomization (MR) studies show conflicting causal associations of genetically predicted serum urate with cardiovascular risk factors (i.e., hypertension, diabetes, lipid profile, and kidney function). This study aimed to robustly investigate a causal relationship between urate and cardiovascular risk factors considering single nucleotide polymorphisms (SNPs) as instrumental variables using two-sample MR and various sensitivity analyses.MethodsData on SNP-urate associations were taken from the Global Urate Genetics Consortium and data on SNP-cardiovascular risk factor associations were taken from various consortia/UK Biobank. SNPs were selected by statistically and biologically driven approaches as instrumental variables. Various sensitivity analyses were performed using different MR methods including inverse variance weighted, MR-Egger, weighted median/mode, MR-PRESSO, and the contamination mixture method.ResultsThe statistically driven approach showed significant causal effects of urate on HDL-C and triglycerides using four of the six MR methods, i.e., every 1 mg/dl increase in genetically predicted urate was associated with 0.047 to 0.103 SD decrease in HDL-C and 0.034 to 0.207 SD increase in triglycerides. The biologically driven approach to selection of SNPs from ABCG2, SLC2A9, SLC17A1, SLC22A11, and SLC22A12 showed consistent causal effects of urate on HDL-C from all methods with 0.038 to 0.057 SD decrease in HDL-C per 1 mg/dl increase of urate, and no evidence of horizontal pleiotropy was detected.ConclusionOur study suggests a significant and robust causal effect of genetically predicted urate on HDL-C. This finding may explain a small proportion (7%) of the association between increased urate and cardiovascular disease but points to urate being a novel cardiac risk factor.

scholarly journals Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study

2018 ◽  
Vol 107 ◽  
pp. 74-86 ◽  
Author(s):  
Liang He ◽  
Irina Culminskaya ◽  
Yury Loika ◽  
Konstantin G. Arbeev ◽  
Olivia Bagley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Mendelian Randomization ◽  
Causal Effects ◽  
Time To Event ◽  
Age Related

scholarly journals Using the MR-Base platform to investigate risk factors and drug targets for thousands of phenotypes

2019 ◽  
Vol 4 ◽  
pp. 113 ◽  
Author(s):  
Venexia M Walker ◽  
Neil M Davies ◽  
Gibran Hemani ◽  
Jie Zheng ◽  
Philip C Haycock ◽  
...  
Keyword(s):  
Risk Factors ◽  
Web Application ◽  
Drug Targets ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
R Package ◽  
Sensitivity Analyses ◽  
Link Type ◽  
Study Results

Mendelian randomization (MR) estimates the causal effect of exposures on outcomes by exploiting genetic variation to address confounding and reverse causation. This method has a broad range of applications, including investigating risk factors and appraising potential targets for intervention. MR-Base has become established as a freely accessible, online platform, which combines a database of complete genome-wide association study results with an interface for performing Mendelian randomization and sensitivity analyses. This allows the user to explore millions of potentially causal associations. MR-Base is available as a web application or as an R package. The technical aspects of the tool have previously been documented in the literature. The present article is complementary to this as it focuses on the applied aspects. Specifically, we describe how MR-Base can be used in several ways, including to perform novel causal analyses, replicate results and enable transparency, amongst others. We also present three use cases, which demonstrate important applications of Mendelian randomization and highlight the benefits of using MR-Base for these types of analyses.

Abstract P011: Cardiovascular Risk Factors and Longevity

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Michelle C Odden ◽  
Andreea Rawlings ◽  
Alice Arnold ◽  
Mary Cushman ◽  
Mary Lou Biggs ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Systolic Blood Pressure ◽  
Cardiovascular Risk Factors ◽  
Old Age ◽  
Repeated Measures ◽  
Ldl Cholesterol ◽  
Low Cardiovascular Risk

Introduction: Cardiovascular disease is the leading cause of mortality in old age, yet there is limited research on the patterns of cardiovascular risk factors that predict survival to 90 years. Hypothesis: The patterns of cardiovascular risk factors that portend longevity will differ from those that confer low cardiovascular risk. Methods: We examined repeated measures of blood pressure, LDL-cholesterol, and BMI from age 67 and survival to 90 years in the Cardiovascular Health Study (CHS). CHS is a prospective study of 5,888 black and white adults in two waves (1989-90 and 1992-93) from Medicare eligibility lists in four counties in the U.S. We restricted to participants aged 67 to 75 years at baseline to control for birth cohort effects and examined repeated measures of cardiovascular risk factors throughout the late-life course. We fit logistic regression models to predict survival to age 90 using generalized estimating equations, and modeled the risk factors as linear, a linear spline, and clinically relevant categories. Models were adjusted for demographics and medication use, and we also examined whether the association of each risk factor with longevity varied by the age of risk factor measurement. Best fit models are presented. Results: Among 3,645 participants in the birth cohort, 1,160 (31.8%) survived to 90 by June 16 th , 2015. Higher systolic blood pressure in early old age was associated with reduced odds for longevity, but there was an interaction with age such that the association crossed the null at 80 years. (Table) Among those with LDL-cholesterol <130 mg/dL, higher LDL-cholesterol was associated with greater longevity; at levels above 130 mg/dL there was no association between LDL-cholesterol and longevity. BMI had a u-shaped association with longevity. Conclusions: In summary, the patterns of risk factors that predict longevity differ from that considered to predict low cardiovascular risk. The risk of high systolic blood pressure appears to depend on the age of blood pressure measurement.

P1532Asymptomatic structural heart disease in individuals without apparent cardiovascular risk factors An unnoticed potential precursor stage of heart failure. Results from the STAAB cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Morbach ◽  
G Gelbrich ◽  
T Tiffe ◽  
F Eichner ◽  
M Breunig ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Failure ◽  
Risk Factor ◽  
Cohort Study ◽  
Heart Disease ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Structural Heart Disease ◽  
Qtc Interval ◽  
Lv Ejection Fraction

Abstract Background and aim Prevention of heart failure (HF) relies on early identification and elimination of cardiovascular risk factors. ACC/AHA guidelines define consecutive asymptomatic precursor stages of HF, i.e. stage A (with risk factors for HF), and stage B (asymptomatic cardiac dysfunction). We aimed to identify frequency and characteristics of individuals at risk for HF, i.e. stage A and B, in the general population. Methods The prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study phenotyped a representative sample of 5000 residents (aged 30–79 y) of a medium sized German town, reporting no previous HF diagnosis. Echocardiography was highly quality-controlled. We applied these definitions: HF stage A: ≥1 risk factor for HF (hypertension, arteriosclerotic disease, diabetes mellitus, obesity, metabolic syndrome), but no structural heart disease (SHD); HF stage B: asymptomatic but SHD [reduced left ventricular (LV) ejection fraction, LV hypertrophy, LV dilation, stenosis or grade 2/3 regurgitation of aortic/mitral valve, grade 2/3 diastolic dysfunction], or prior myocardial infarction; Normal (N): no risk factor and no SHD. We focused on subjects in stage B without apparent cardiovascular risk factors qualifying for A (B-not-A) compared to those with risk factors (BA) and N. The first half of the sample (n=2473) served as derivation set (D), the second half (n=2434) as validation set (V). Results We found 42% (D)/45% (V) of subjects in stage A, and 18% (D)/17% (V) in stage B. Among stage B subjects, 31% (D)/29% (V) were B-not-A. Compared to BA, B-not-A subjects were younger [47 vs. 63 y (D)/50 vs 63 years (V); both p<0.001] and more often female [78% vs 56% (D)/79% vs 62% (V); both p<0.001], had higher LV ejection fraction [59% vs 56% (D)/53% vs 48% (V); both p<0.05], lower E/e' [6.7 vs 9.9 (D)/6.9 vs. 9.3 (V); both p<0.001], higher LV volume [64 vs 59 mL/m2 (D)/54 vs 48 mL/m2 (V); both p≤0.01], lower hemoglobin [13.3 vs 13.9 g/dL (D, p=0.02)/13.4 vs 13.8 g/dL (V, p=0.08); both adjusted for sex], and lower QTc interval [423 vs 433 ms (D)/427 vs 438 ms (V); both p≤0.001). Compared to N, subjects in B-not-A were more often female [78% vs 56% (D)/79% vs 61% (V); both p<0.001], had larger QTc interval [423 vs 418 ms (D)/427 vs 420 ms (V); both p<0.05], and more often anemia [11% vs 5% (D, p=0.02)/9% vs 5% (V, p=0.12)]. Conclusions We confirmed, by extensive internal validation, the presence of a hitherto undescribed group of individuals with relevant myocardial alterations, but lacking respective risk factors. Since algorithms in primary prevention do not include echocardiography, this subgroup might be missed. Further investigations should 1) externally validate our finding, 2) study the prognostic course of subjects in group B-not-A, and 3) elaborate the material differences between B-not-A and N to identify potential further novel risk factors for HF. Acknowledgement/Funding German Ministry of Research and Education within the Comprehensive Heart Failure Centre Würzburg (BMBF 01EO1004 and 01EO1504)

Circulating adiponectin levels and systemic lupus erythematosus: a two-sample Mendelian randomization study

Rheumatology ◽  
2020 ◽  
Author(s):  
Yi-Lin Dan ◽  
Peng Wang ◽  
Zhongle Cheng ◽  
Qian Wu ◽  
Xue-Rong Wang ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Instrumental Variables ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Causal Effects ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Inverse Variance ◽  
Weighted Median

Abstract Objectives Several studies have reported increased serum/plasma adiponectin levels in SLE patients. This study was performed to estimate the causal effects of circulating adiponectin levels on SLE. Methods We selected nine independent single-nucleotide polymorphisms that were associated with circulating adiponectin levels (P &lt; 5 × 10−8) as instrumental variables from a published genome-wide association study (GWAS) meta-analysis. The corresponding effects between instrumental variables and outcome (SLE) were obtained from an SLE GWAS analysis, including 7219 cases with 15 991 controls of European ancestry. Two-sample Mendelian randomization (MR) analyses with inverse-variance weighted, MR-Egger regression, weighted median and weight mode methods were used to evaluate the causal effects. Results The results of inverse-variance weighted methods showed no significantly causal associations of genetically predicted circulating adiponectin levels and the risk for SLE, with an odds ratio (OR) of 1.38 (95% CI 0.91, 1.35; P = 0.130). MR-Egger [OR 1.62 (95% CI 0.85, 1.54), P = 0.195], weighted median [OR 1.37 (95% CI 0.82, 1.35), P = 0.235) and weighted mode methods [OR 1.39 (95% CI 0.86, 1.38), P = 0.219] also supported no significant associations of circulating adiponectin levels and the risk for SLE. Furthermore, MR analyses in using SLE-associated single-nucleotide polymorphisms as an instrumental variable showed no associations of genetically predicted risk of SLE with circulating adiponectin levels. Conclusion Our study did not find evidence for a causal relationship between circulating adiponectin levels and the risk of SLE or of a causal effect of SLE on circulating adiponectin levels.

scholarly journals Cardiovascular risk factors affect hippocampal microvasculature in early AD

2010 ◽  
Vol 1 (4) ◽  
Author(s):  
Elizabeth Schwartz ◽  
Bridget Wicinski ◽  
James Schmeidler ◽  
Vahram Haroutunian ◽  
Patrick Hof
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Hippocampal Ca1 ◽  
Density Values ◽  
Mean And Variance ◽  
Hippocampal Ca1 Field ◽  
Early Alzheimer’S Disease ◽  
Human Brains

AbstractThere is growing clinical and neuropathologic evidence suggesting that cognitive decline in early Alzheimer’s disease (AD) is aggravated by a synergistic relationship between AD and cerebrovascular disease associated with cardiovascular risk factors such as diabetes and hypertension. Here we used the stereologic “Space Balls” method to investigate the relationships between AD pathology and cardiovascular risk factors in postmortem human brains of patients with hypertension and diabetes in two groups — one consisting of cases with AD diagnosis and one of cases without. Hippocampal CA1 and CA3 microvasculature length density estimates were generated to characterize quantitatively the contribution of cardiovascular risk factors to the severity of neuropathologic changes. Our main finding is that the mean and variance of length density values in the AD group were significantly increased from the non-AD group, regardless of the absence or presence of a cardiovascular risk factor. An additional finding is that in the AD group without a risk factor, dementia severity correlated with amount of length density change in the CA1 field—this correlation did not exist in the AD groups with risk factors. Our findings suggest a role for cardiovascular risk factors in quantifiable change of hippocampal CA1 field microvasculature, as well as suggest a possible role of cardiovascular risk factors in altering microvasculature pathology in the presence of AD.

scholarly journals Association among sickle cell trait, fitness, and cardiovascular risk factors in CARDIA

Blood ◽  
2017 ◽  
Vol 129 (6) ◽  
pp. 723-728 ◽  
Author(s):  
Robert I. Liem ◽  
Cheeling Chan ◽  
Thanh-Huyen T. Vu ◽  
Myriam Fornage ◽  
Alexis A. Thompson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
African Americans ◽  
Cardiovascular Risk Factors ◽  
Sickle Cell ◽  
Independent Risk Factor ◽  
Sickle Cell Trait ◽  
Key Points

Key Points SCT status is not significantly associated with longitudinal changes in fitness among African Americans. SCT status is not an independent risk factor for hypertension, diabetes, or metabolic syndrome among African Americans.

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