Association of Lipoprotein (a) variants with risk of cardiovascular disease: a Mendelian randomization study

Abstract Background There is a well-documented empirical relationship between lipoprotein (a) [Lp(a)] and cardiovascular disease (CVD); however, causal evidence, especially from the Chinese population, is lacking. Therefore, this study aims to estimate the causal association between variants in genes affecting Lp(a) concentrations and CVD in people of Han Chinese ethnicity. Methods Two-sample Mendelian randomization analysis was used to assess the causal effect of Lp(a) concentrations on the risk of CVD. Summary statistics for Lp(a) variants were obtained from 1256 individuals in the Cohort Study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei. Data on associations between single-nucleotide polymorphisms (SNPs) and CVD were obtained from recently published genome-wide association studies. Results Thirteen SNPs associated with Lp(a) levels in the Han Chinese population were used as instrumental variables. Genetically elevated Lp(a) was inversely associated with the risk of atrial fibrillation [odds ratio (OR), 0.94; 95% confidence interval (95%CI), 0.901–0.987; P = 0.012)], the risk of arrhythmia (OR, 0.96; 95%CI, 0.941–0.990; P = 0.005), the left ventricular mass index (OR, 0.97; 95%CI, 0.949–1.000; P = 0.048), and the left ventricular internal dimension in diastole (OR, 0.97; 95%CI, 0.950–0.997; P = 0.028) according to the inverse-variance weighted method. No significant association was observed for congestive heart failure (OR, 0.99; 95% CI, 0.950–1.038; P = 0.766), ischemic stroke (OR, 1.01; 95%CI, 0.981–1.046; P = 0.422), and left ventricular internal dimension in systole (OR, 0.98; 95%CI, 0.960–1.009; P = 0.214). Conclusions This study provided evidence that genetically elevated Lp(a) was inversely associated with atrial fibrillation, arrhythmia, the left ventricular mass index and the left ventricular internal dimension in diastole, but not with congestive heart failure, ischemic stroke, and the left ventricular internal dimension in systole in the Han Chinese population. Further research is needed to identify the mechanism underlying these results and determine whether genetically elevated Lp(a) increases the risk of coronary heart disease or other CVD subtypes.

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Abstract MP13: Plasma Homocysteine is Causally Associated With Ischemic Stroke in a Han Chinese Population: A Mendelian Randomization Study

Circulation ◽

10.1161/circ.139.suppl_1.mp13 ◽

2019 ◽

Vol 139 (Suppl_1) ◽

Author(s):

Zhengbao Zhu ◽

Tanika N. Kelly ◽

Yonghong Zhang ◽

Changwei Li ◽

Aili Wang ◽

...

Keyword(s):

Ischemic Stroke ◽

Chinese Population ◽

Mendelian Randomization ◽

Plasma Homocysteine ◽

Han Chinese ◽

Han Chinese Population

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GW25-e0274 A polymorphism rs11614913 in pre-microRNAs may be associated with atrial fibrillation in Han Chinese population

Journal of the American College of Cardiology ◽

10.1016/j.jacc.2014.06.231 ◽

2014 ◽

Vol 64 (16) ◽

pp. C47-C48 ◽

Cited By ~ 1

Author(s):

Su Yamin ◽

Li Jun ◽

Chen Feng ◽

Geng Haihua ◽

Pan Min

Keyword(s):

Atrial Fibrillation ◽

Chinese Population ◽

Han Chinese ◽

Han Chinese Population

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The effect of geographical indices on left ventricular structure in healthy Han Chinese population

International Journal of Biometeorology ◽

10.1007/s00484-016-1212-1 ◽

2016 ◽

Vol 61 (2) ◽

pp. 303-311

Author(s):

Minyi Cen ◽

Miao Ge ◽

Yonglin Liu ◽

Congxia Wang ◽

Shaofang Yang

Keyword(s):

Chinese Population ◽

Left Ventricular ◽

Han Chinese ◽

Han Chinese Population ◽

Left Ventricular Structure ◽

Ventricular Structure ◽

Geographical Indices

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Mendelian randomization study on atrial fibrillation and cardiovascular disease subtypes

Scientific Reports ◽

10.1038/s41598-021-98058-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Man Ki Kwok ◽

Catherine Mary Schooling

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cardiovascular Disease ◽

Ischemic Stroke ◽

Mendelian Randomization ◽

Late Onset ◽

Cardioembolic Stroke ◽

Sensitivity Analyses ◽

Subdural Hemorrhage ◽

Arterial Thromboembolism

AbstractAtrial fibrillation (AF) has been associated with numerous diseases. However, whether AF is a cause or consequence of these diseases is uncertain. To clarify, we assessed the causal role of AF on ischemic heart disease (IHD), stroke, other cardiovascular disease (CVD) subtypes, type 2 diabetes mellitus (T2DM), and late-onset AD using bi-directional two-sample Mendelian randomization (MR) among people primarily of European descent. Genetically predicted log odds of AF was associated with any stroke (odds ratio (OR) 1.22, 95% CI 1.18 to 1.27), particularly cardioembolic stroke and possibly subdural hemorrhage, with sensitivity analyses showing similar positive findings. Genetically predicted AF was also associated with arterial thromboembolism (1.32, 1.13 to 1.53), and heart failure (1.26, 1.21 to 1.30). No association of genetically predicted AF with IHD, T2DM, cognitive function, or late-onset AD was found. Conversely, genetically predicted IHD, heart failure and possibly ischemic stroke, particularly cardioembolic stroke, were positively associated with AF. Atrial fibrillation plays a role in any stroke, arterial thromboembolism, and heart failure, corroborating current clinical guidelines on the importance of preventing these complications by effective AF management. In addition, patients with IHD, heart failure or possibly ischemic stroke might be predisposed to developing AF, with implications for management.

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Abstract WP251: A Mendelian Randomization Study of Alcohol Intake and Ischemic Stroke in a Han Chinese Population

Stroke ◽

10.1161/str.50.suppl_1.wp251 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Yonghong Zhang ◽

Mengyao Shi ◽

Changwei Li ◽

Aili Wang ◽

Tan Xu ◽

...

Keyword(s):

Ischemic Stroke ◽

Chinese Population ◽

Alcohol Intake ◽

Mendelian Randomization ◽

Han Chinese ◽

Han Chinese Population

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Abstract WP252: A Mendelian Randomization Study of Plasma Homocysteine and Ischemic Stroke in a Han Chinese Population

Stroke ◽

10.1161/str.50.suppl_1.wp252 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Tanika Kelly ◽

Yonghong Zhang ◽

Changwei Li ◽

Aili Wang ◽

Tan Xu ◽

...

Keyword(s):

Ischemic Stroke ◽

Chinese Population ◽

Mendelian Randomization ◽

Plasma Homocysteine ◽

Han Chinese ◽

Han Chinese Population

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Left Atrioventricular Coupling Index as a Prognostic Marker of Cardiovascular Events: The MESA Study

Hypertension ◽

10.1161/hypertensionaha.121.17339 ◽

2021 ◽

Author(s):

Theo Pezel ◽

Bharath Ambale Venkatesh ◽

Henrique Doria De Vasconcellos ◽

Yoko Kato ◽

Mahsima Shabani ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cardiovascular Disease ◽

Coronary Heart Disease ◽

Heart Disease ◽

Left Atrial ◽

Cardiovascular Events ◽

Left Ventricular ◽

Hazard Ratio ◽

Coronary Heart Disease Death

Both left atrial and left ventricular functional parameters influence the prognosis of patients with cardiovascular diseases. This study aimed to investigate the prognostic value of a novel left atrioventricular coupling index (LACI) in a population without history of cardiovascular diseases at baseline. Participants of the Multi-Ethnic Study of Atherosclerosis who underwent a baseline cardiovascular magnetic resonance study were analyzed. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular end-diastolic volume. Cox proportional hazard models were used to evaluate the association between LACI and atrial fibrillation, heart failure, coronary heart disease death, and hard cardiovascular disease defined by myocardial infarction, resuscitated cardiac arrest, fatal and nonfatal stroke, or coronary heart disease death. Among the 4124 participants (61.5±10.1 years, 47.4% men), 1074 cardiovascular events were observed (mean follow-up, 13.0±3.2 years). Greater LACI was independently associated with atrial fibrillation (hazard ratio, 1.86 [95% CI, 1.69–2.04]), heart failure (hazard ratio, 1.50 [95% CI, 1.38–1.62]), hard cardiovascular disease (1.23 [95% CI, 1.13–1.34]), and coronary heart disease death (hazard ratio, 1.29 [95% CI, 1.15–1.45]; all P <0.0001). After adjustment for traditional cardiovascular risk factors, LACI showed significant improvement in model discrimination and reclassification compared with currently used standard models to predict outcomes. LACI is a strong predictor for the incidence of heart failure, atrial fibrillation, hard cardiovascular disease, and coronary heart disease death. LACI has incremental prognostic value to predict cardiovascular events over traditional risk factors and better discrimination and reclassification power compared with individual left atrial or left ventricular parameters.

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ErbB4 Gene Polymorphism Is Associated With the Risk and Prognosis of Congestive Heart Failure in a Northern Han Chinese Population

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2016.01.013 ◽

2016 ◽

Vol 22 (9) ◽

pp. 700-709 ◽

Cited By ~ 2

Author(s):

Yunhong Wang ◽

Yuhui Zhang ◽

Tao An ◽

Rongcheng Zhang ◽

Xuemei Zhao ◽

...

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Gene Polymorphism ◽

Chinese Population ◽

Han Chinese ◽

Han Chinese Population ◽

Erbb4 Gene

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Cardiovascular Events after New-Onset Atrial Fibrillation in Adults with CKD: Results from the Chronic Renal Insufficiency Cohort (CRIC) Study

Journal of the American Society of Nephrology ◽

10.1681/asn.2018050514 ◽

2018 ◽

Vol 29 (12) ◽

pp. 2859-2869 ◽

Cited By ~ 15

Author(s):

Nisha Bansal ◽

Dawei Xie ◽

Daohang Sha ◽

Lawrence J. Appel ◽

Rajat Deo ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Atrial Fibrillation ◽

Cardiovascular Disease ◽

Renal Insufficiency ◽

Chronic Renal Insufficiency ◽

Cox Regression ◽

Mineral Metabolism ◽

Left Ventricular ◽

New Onset

BackgroundAtrial fibrillation (AF), the most common sustained arrhythmia in CKD, is associated with poor clinical outcomes in both patients without CKD and patients with dialysis-treated ESRD. However, less is known about AF-associated outcomes in patients with CKD who do not require dialysis.MethodsTo prospectively examine the association of new-onset AF with subsequent risks of cardiovascular disease events and death among adults with CKD, we studied participants enrolled in the Chronic Renal Insufficiency Cohort Study who did not have AF at baseline. Outcomes included heart failure, myocardial infarction, stroke, and death occurring after diagnosis of AF. We used Cox regression models and marginal structural models to examine the association of incident AF with subsequent risk of cardiovascular disease events and death, adjusting for patient characteristics, laboratory values, and medication use.ResultsAmong 3080 participants, 323 (10.5%) developed incident AF during a mean 6.1 years of follow-up. Compared with participants who did not develop AF, those who did had higher adjusted rates of heart failure (hazard ratio [HR], 5.17; 95% confidence interval [95% CI], 3.89 to 6.87), myocardial infarction (HR, 3.64; 95% CI, 2.50 to 5.31), stroke (HR, 2.66; 95% CI, 1.50 to 4.74), and death (HR, 3.30; 95% CI, 2.65 to 4.12). These associations remained robust with additional adjustment for biomarkers of inflammation, cardiac stress, and mineral metabolism; left ventricular mass; ejection fraction; and left atrial diameter.ConclusionsIncident AF is independently associated with two- to five-fold increased rates of developing subsequent heart failure, myocardial infarction, stroke, or death in adults with CKD. These findings have important implications for cardiovascular risk reduction.

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