scholarly journals Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization

2019 ◽  
Vol 104 (11) ◽  
pp. 5595-5600 ◽  
Author(s):  
Håkan Melhus ◽  
Karl Michaëlsson ◽  
Susanna C Larsson
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Parathyroid Hormone ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Serum Parathyroid Hormone ◽  
Increased Risk ◽  
Artery Disease

Abstract Context Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown. Objective We used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD). Design, Setting, and Participants Five single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases). Main Outcome Measure OR of CAD per genetically predicted one SD increase of S-PTH concentrations. Results Genetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (∼70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses. Conclusion Genetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.

scholarly journals The impact of serum 25-hydroxyvitamin D, calcium, and parathyroid hormone levels on the risk of coronary artery disease in patients with diabetes: a Mendelian randomization study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Songzan Chen ◽  
Fangkun Yang ◽  
Tian Xu ◽  
Yao Wang ◽  
Kaijie Zhang ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Parathyroid Hormone ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Serum 25Ohd ◽  
Hydroxyvitamin D ◽  
Patients With Diabetes ◽  
25 Hydroxyvitamin D ◽  
Artery Disease

Abstract Background To investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach. Methods Genetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses. Results Six, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 – 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 – 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses. Conclusions/interpretation Serum 25OHD, Ca and PTH levels may not be causally associated with the risk of CAD in patients with diabetes.

scholarly journals Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Martin Bahls ◽  
Michael F. Leitzmann ◽  
André Karch ◽  
Alexander Teumer ◽  
Marcus Dörr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Artery Disease

Abstract Aims Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. Methods and results We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. Conclusions These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. Graphic abstract

No causal effects of plasma homocysteine levels on the risk of coronary heart disease or acute myocardial infarction: A Mendelian randomization study

2019 ◽  
pp. 204748731989467 ◽  
Author(s):  
Liu Miao ◽  
Guo-Xiong Deng ◽  
Rui-Xing Yin ◽  
Rong-Jun Nie ◽  
Shuo Yang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Plasma Homocysteine ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Artery Disease

Background Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction. Methods A two-sample Mendelian randomization study on disease was conducted, i.e. “coronary heart disease” ( n = 184,305) and “acute myocardial infarction” ( n = 181,875). Nine single nucleotide polymorphisms, which were genome-wide significantly associated with plasma homocysteine levels in 57,644 subjects from the Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium genome-wide association study and were known to be associated at p < 5×10–8, were used as an instrumental variable. Results None of the nine single nucleotide polymorphisms were associated with coronary heart disease or acute myocardial infarction ( p > 0.05 for all). Mendelian randomization analysis revealed no causal effects of plasma homocysteine levels, either on coronary heart disease (inverse variance weighted; odds ratio = 1.015, 95% confidence interval = 0.923–1.106, p = 0.752) or on acute myocardial infarction (inverse variance weighted; odds ratio = 1.037, 95% confidence interval = 0.932–1.142, p = 0.499). The results were consistent in sensitivity analyses using the weighted median and Mendelian randomization-Egger methods, and no directional pleiotropy ( p = 0.213 for coronary heart disease and p = 0.343 for acute myocardial infarction) was observed. Sensitivity analyses confirmed that plasma homocysteine levels were not significantly associated with coronary heart disease or acute myocardial infarction. Conclusions The findings from this Mendelian randomization study indicate no causal relationship between plasma homocysteine levels and coronary heart disease or acute myocardial infarction. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

Abstract P380: Coronary Artery Disease Extent is Predictive of Heart Failure Incidence After Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Yariv Gerber ◽  
Susan A Weston ◽  
Maurice E Sarano ◽  
Sheila M Manemann ◽  
Alanna M Chamberlain ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Proportional Hazards ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Disease Extent ◽  
Increased Risk ◽  
Artery Disease

Background: Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined. Subjects and Methods: Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data. Results: During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table). Conclusions: The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.

scholarly journals Comparative Study between Diabetic and non- Diabetic Patients Regarding Prevalence of Coronary Artery Disease and Plaque Composition by Multi-detector CT Coronary Angiography

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H A Morsy ◽  
L A Habib ◽  
E H Abdeldayem ◽  
A I Sayed
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Artery ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Increased Risk ◽  
Artery Disease ◽  
Msct Angiography

Abstract Diabetes is known to be a major cardiovascular risk factor associated with significantly increased morbidity and mortality and particularly increased risk of major cardiac events especially myocardial infarction as a manifestation of highly incident coronary artery disease (CAD).This can lead to decreased life expectation and life quality. Major cause for myocardial infarction is plaque rupture. Prevalence of obstructive and non-obstructive plaques is increased in diabetic patients. Background and Objectives The prevalence of coronary heart disease in diabetic patients compared to non- diabetics and evaluating the composition of the plaque in diseased individuals in both groups by usage of multislice computed tomography (MSCT) angiography . Subjects and Methods A total of 80 consecutive MSCT angiography examinations were performed between August 2017 and June 2018. Of these, the patients were evaluated for the presence and type of atherosclerotic plaque and severity of luminal narrowing. Results Eighty (40 in the diabetic group and 40 in the non-diabetic group) patients underwent MSCT angiography with DM prevalence of 0.212 (95% Cl for AOR 0.056 -1.896). Among them, 20 patients (50 %) in the diabetic group and 14 patients (35 %) in the non-diabetic group had +ve coronary heart disease, 33.3 % had significant and moderately significant coronary narrowing on diabetic group and 31.3 % in non-diabetic group on MSCT angiography. Diabetic patients had more soft plaque compared with non-diabetic patients. Conclusion DM is not an independent factor for the disease occurrence in coronary artery disease but is a dependent factor in the association of other risk factors such as smoking ,hypertension and dyslipidemia.

scholarly journals Endometriosis and New-Onset Coronary Artery Disease in Taiwan: A Nationwide Population-Based Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Chun-Hui Wei ◽  
Renin Chang ◽  
Yu Hsun Wan ◽  
Yao-Min Hung ◽  
James Cheng-Chung Wei
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Age Groups ◽  
Population Based ◽  
Sensitivity Analyses ◽  
Increased Risk ◽  
Artery Disease ◽  
Stratified Analysis ◽  
New Onset

Endometriosis (EM) with chronic inflammation may accelerate the progression of atherosclerosis. Currently, no large or randomized clinical studies have assessed the incidence of cardiovascular events in patients with endometriosis in Asia to investigate whether incident EM is associated with a higher risk of new-onset coronary artery disease (CAD). In this study of a nationwide cohort in Taiwan, we identified 13,988 patients with newly diagnosed EM from 1 January, 2000, through 31 December, 2012. EM and non-EM groups were matched by propensity score at a ratio of 1:1. Of a total 27,976 participants, 358 developed CAD. The incidence rate in the EM group was higher than that in the non-EM group (1.8 per 1,000 person-years vs. 1.3 per 1,000 person-years) during the follow-up period. The adjusted hazard ratio (aHR) of CAD for the EM group was 1.52 with a 95% confidence interval (1.23–1.87, p &lt; 0.001) after adjusting for demographic characteristics, comorbidities, surgical procedures, frequency of outpatient visits, and medications. Stratified analysis revealed that, among four age groups (20–39, 40–49, 50–54, and above 55 years), the 20–39 years sub-group was associated with a higher risk of CAD (aHR, 1.73; 95% CI, 1.16–2.59, p = 0.008). Several sensitivity analyses were conducted for cross-validation, and it showed consistent positive findings. In conclusion, this cohort study revealed that patients with symptomatic EM in Taiwan were associated with increased risk of subsequent CAD than patients without medical records of EM. Further prospective studies are needed to confirm this causal relationship.

scholarly journals Low Pain Tolerance Is Associated With Coronary Angiography, Coronary Artery Disease, and Mortality: The Tromsø Study

2021 ◽  
Author(s):  
Kristina Fladseth ◽  
Haakon Lindekleiv ◽  
Christopher Nielsen ◽  
Andrea Øhrn ◽  
Andreas Kristensen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Time Scale ◽  
Cold Pressor ◽  
Pain Tolerance ◽  
Increased Risk ◽  
Cold Pressor Pain ◽  
Artery Disease

Background The initial presentation to coronary angiography and extent of coronary artery disease (CAD) vary greatly among patients, from ischemia with no obstructive CAD to myocardial infarction with 3‐vessel disease. Pain tolerance has been suggested as a potential mechanism for the variation in presentation of CAD. We aimed to investigate the association between pain tolerance, coronary angiography, CAD, and death. Methods and Results We identified 9576 participants in the Tromsø Study (2007–2008) who completed the cold‐pressor pain test, and had no prior history of CAD. The median follow‐up time was 10.4 years. We applied Cox‐regression models with age as time‐scale to calculate hazard ratios (HR). More women than men aborted the cold pressor test (39% versus 23%). Participants with low pain tolerance had 19% increased risk of coronary angiography (HR, 1.19 [95% CI, 1.03–1.38]) and 22% increased risk of obstructive CAD (HR, 1.22 [95% CI, 1.01–1.47]) adjusted by age as time‐scale and sex. Among women who underwent coronary angiography, low pain tolerance was associated with 54% increased risk of obstructive CAD (HR, 1.54 [95% CI, 1.09–2.18]) compared with high pain tolerance. There was no association between pain tolerance and nonobstructive CAD or clinical presentation to coronary angiography (ie, stable angina, unstable angina, and myocardial infarction). Participants with low pain tolerance had increased risk of mortality after adjustment for CAD and cardiovascular risk factors (HR, 1.40 [95% CI, 1.19–1.64]). Conclusions Low cold pressor pain tolerance is associated with a higher risk of coronary angiography and death.

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