scholarly journals Investigating Effects of Plasma Apolipoprotein E on Ischemic Heart Disease Using Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2215
Author(s):  
Meng-Yu Li ◽  
Man-Ki Kwok ◽  
Catherine Mary Schooling
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Apolipoprotein E ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Ischemic Heart ◽  
Direct Effects ◽  
Apoe Isoforms ◽  
Plasma Apolipoprotein

Background: Observationally plasma apolipoprotein E (apoE) is positively associated with ischemic heart disease (IHD). A Mendelian randomization (MR) study suggesting apoE is unrelated to cardiovascular mortality did not consider specific isoforms. We used MR to obtain estimates of plasma apoE2, apoE3 and apoE4 on IHD, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, triglycerides and apolipoprotein B (apoB). Methods: We obtained independent genetic instruments from proteome genome-wide association studies (GWAS) and applied them to large outcome GWAS. We used univariable MR to assess the role of each isoform and multivariable MR to assess direct effects. Results: In univariable MR, apoE4 was positively associated with IHD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.01 to 1.09), but apoE2 and apoE3 were less clearly associated. Using multivariable MR an association of apoE2 with IHD (OR 1.16, 95% CI 0.98 to 1.38) could not be excluded, and associations of apoE3 and apoE4 with IHD were not obvious. In univariable MR, apoE2 and apoE4 were positively associated with apoB, and a positive association of apoE2 with LDL cholesterol could not be excluded. Using multivariable MR apoE2 was positively associated with LDL cholesterol, and associations with apoB could not be excluded. After adjusting for apoB, no direct effects of apoE isoforms on IHD were evident. Conclusions: Plasma apoE2 and apoE4 may play a role in lipid modulation and IHD. Whether apoE could be a potential therapeutic target requires further clarification when larger genetic studies of apoE isoforms are available.

scholarly journals Associations of Arachidonic Acid Synthesis with Cardiovascular Risk Factors and Relation to Ischemic Heart Disease and Stroke: A Univariable and Multivariable Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1489
Author(s):  
Ting Zhang ◽  
Shiu-Lun Au Yeung ◽  
C. Mary Schooling
Keyword(s):  
Risk Factors ◽  
Arachidonic Acid ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Plasma Phospholipid ◽  
Ischemic Heart ◽  
Cvd Risk ◽  
Markers Of Inflammation

Arachidonic acid (AA), a major long-chain omega-6 polyunsaturated fatty acid, is associated with ischemic heart disease (IHD) and stroke. We assessed bi-directional associations of AA synthesis reflected by plasma phospholipid AA with CVD risk factors, and identified mediators of associations of AA with IHD and stroke using Mendelian randomization (MR). We used two-sample MR to assess bi-directional associations of AA synthesis with lipids, blood pressure, adiposity, and markers of inflammation and coagulation. We used multivariable MR to assess mediators of associations of AA with IHD and stroke. Genetically predicted AA (% of total fatty acids increase) was positively associated with apolipoprotein B (ApoB, 0.022 standard deviations (SD), 95% confidence interval (CI) 0.010, 0.034), high-density (0.030 SD, 95% CI 0.012, 0.049) and low-density lipoprotein cholesterol (LDL-C, 0.016 SD, 95% CI 0.004, 0.027) and lower triglycerides (−0.031 SD, 95% CI −0.049, −0.012) but not with other traits. Genetically predicted these traits gave no association with AA. The association of AA with IHD was attenuated adjusting for ApoB or LDL-C. Genetically predicted AA was associated with lipids but not other traits. Given ApoB is thought to be the key lipid in IHD, the association of AA with IHD is likely mediated by ApoB.

scholarly journals Changes in the prevalence of metabolic syndrome and smoking habits during a 10-year period and relation between these risk factors and ischemic heart disease among men aged 45–64 years

Medicina ◽  
2008 ◽  
Vol 44 (5) ◽  
pp. 400 ◽  
Author(s):  
Dalia Lukšienė ◽  
Liucija Černiauskienė ◽  
Lilija Margevičienė ◽  
Abdonas Tamošiūnas
Keyword(s):  
Myocardial Infarction ◽  
Metabolic Syndrome ◽  
Heart Disease ◽  
Angina Pectoris ◽  
Ischemic Heart Disease ◽  
Density Lipoprotein ◽  
Epidemiological Studies ◽  
Ischemic Heart ◽  
Smoking Habits ◽  
Previous Myocardial Infarction

The aim of this work was to compare the prevalence of metabolic syndrome and smoking habits smokingduring a 10-year period and to evaluate the association between metabolic syndrome and smoking habits, and ischemic heart disease among Kaunas men aged 45–64 years. Material and methods. In this study, we have used data from two epidemiological studies, which had been carried out according to the MONICA study protocol (359 men aged 45–64 years were enrolled in 1992–1993 and 408 men aged 45–64 years – in 2001–2002). The association between metabolic syndrome and smoking habits, and ischemic heart disease was established according to the data of 2001–2002 years. Ischemic heart disease was diagnosed based on the following criteria: previous myocardial infarction, angina pectoris, or ischemic changes in electrocardiogram. Metabolic syndrome was defined by Adult Treatment Panel III (ATP III) criteria. Results. The prevalence of ischemic heart disease did not change among men aged 45–64 years during a 10-year period. During this period, the decreased prevalence of metabolic syndrome was observed; decreased rate of hyperglycemia, decreased high-density lipoprotein cholesterol level, increased rate of hypertriglyceridemia, and increased waist circumference were noted. During this period, the proportion of regular male smokers increased significantly. After the evaluation of association between and metabolic syndrome and smoking habits, and ischemic heart disease (according to the data of 2001–2002 years), it was determined that the highest rate of ischemic heart disease was among regular smokers with metabolic syndrome (32.3%), and the lowest rate of ischemic heart disease was noted among men who had never smoked and were without metabolic syndrome (11.6%) (OR=3.63; P=0.013). The highest rate of previous myocardial infarction and/or angina pectoris was determined among regular smokers with metabolic syndrome (19.4%), and the lowest rate of ischemic heart disease was determined among men who had never smoked and were without metabolic syndrome (3.6%) (OR=6.43; P=0.008). Conclusion. Combination of metabolic syndrome and smoking is significantly associated with ischemic heart disease among men aged 45–64 years.

scholarly journals Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

2016 ◽  
Vol 62 (4) ◽  
pp. 593-604 ◽  
Author(s):  
Anne-Marie K Jepsen ◽  
Anne Langsted ◽  
Anette Varbo ◽  
Lia E Bang ◽  
Pia R Kamstrup ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ldl Cholesterol ◽  
Hdl Cholesterol ◽  
Hazard Ratio ◽  
Residual Risk ◽  
Ischemic Heart ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Remnant Cholesterol

Abstract BACKGROUND Increased concentrations of remnant cholesterol are causally associated with increased risk of ischemic heart disease. We tested the hypothesis that increased remnant cholesterol is a risk factor for all-cause mortality in patients with ischemic heart disease. METHODS We included 5414 Danish patients diagnosed with ischemic heart disease. Patients on statins were not excluded. Calculated remnant cholesterol was nonfasting total cholesterol minus LDL and HDL cholesterol. During 35836 person-years of follow-up, 1319 patients died. RESULTS We examined both calculated and directly measured remnant cholesterol; importantly, however, measured remnant cholesterol made up only 9% of calculated remnant cholesterol at nonfasting triglyceride concentrations <1 mmol/L (89 mg/dL) and only 43% at triglycerides >5 mmol/L (443 mg/dL). Multivariable-adjusted hazard ratios for all-cause mortality compared with patients with calculated remnant cholesterol concentrations in the 0 to 60th percentiles were 1.2 (95% CI, 1.1–1.4) for patients in the 61st to 80th percentiles, 1.3 (1.1–1.5) for the 81st to 90th percentiles, 1.5 (1.1–1.8) for the 91st to 95th percentiles, and 1.6 (1.2–2.0) for patients in the 96th to 100th percentiles (trend, P < 0.001). Corresponding values for measured remnant cholesterol were 1.0 (0.8–1.1), 1.2 (1.0–1.4), 1.1 (0.9–1.5), and 1.3 (1.1–1.7) (trend, P = 0.006), and for measured LDL cholesterol 1.0 (0.9–1.1), 1.0 (0.8–1.2), 1.0 (0.8–1.3), and 1.1 (0.8–1.4) (trend, P = 0.88). Cumulative survival was reduced in patients with calculated remnant cholesterol ≥1 mmol/L (39 mg/dL) vs <1 mmol/L [log-rank, P = 9 × 10−6; hazard ratio 1.3 (1.2–1.5)], but not in patients with measured LDL cholesterol ≥3 mmol/L (116 mg/dL) vs <3 mmol/L [P = 0.76; hazard ratio 1.0 (0.9–1.1)]. CONCLUSIONS Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all-cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant cholesterol explain part of the residual risk of all-cause mortality in patients with ischemic heart disease.

scholarly journals Apolipoprotein E genotype: epsilon32 women are protected while epsilon43 and epsilon44 men are susceptible to ischemic heart disease

2000 ◽  
Vol 35 (5) ◽  
pp. 1192-1199 ◽  
Author(s):  
Ruth Frikke-Schmidt ◽  
Anne Tybjærg-Hansen ◽  
Rolf Steffensen ◽  
Gorm Jensen ◽  
Børge G Nordestgaard
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Apolipoprotein E ◽  
Ischemic Heart ◽  
Apolipoprotein E Genotype

scholarly journals Small Dense Low-Density Lipoprotein: Biomarker or Potential Drug Target?

2019 ◽  
Vol 55 (02) ◽  
pp. 092-097
Author(s):  
Basabdatta Samanta
Keyword(s):  
At Risk ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Adverse Outcomes ◽  
Ischemic Heart ◽  
Low Density ◽  
Treatment And Prevention ◽  
Artery Disease

AbstractIschemic heart disease is currently an epidemic affecting individuals worldwide. Increased incidence along with earlier onset of disease has led to the constant search for biomarkers that will help in earlier identification and treatment of at risk individuals. Small dense low-density lipoprotein (sdLDL) is the atherogenic subtype of low-density lipoprotein (LDL). It is smaller in size and higher in density in comparison to other LDL subtypes. Higher levels of sdLDL have beenfound to be associated with increased incidence of ischemic heart disease and adverse outcomes. Properties including decreased resistance to oxidative stress and prolonged residence time in the circulation account for its increased atherogenic potential. Hence intervention approaches targeting sdLDL directly in at risk individuals may be beneficial.Genetic, lifestyle, and environmental factors affect sdLDL levels.But the main determining factor is the level of triglycerides (TGs). Higher TG levels are associated with higher levels of very low density lipoprotein (VLDL) 1 and sdLDL. Various drugs have been used for targeting sdLDL with varying outcomes; drugs tried out include statins, fibrates, niacin, cholesterol ester transfer protein inhibitors and sodium-glucose co-transporter-2 inhibitors. Future prospects include modification of enzymes involved in fatty acid and TG synthesis, for example, lipoprotein lipase and acyl CoA carboxylase. However, further research is still necessary to draw clear guidelines for sdLDL reduction therapy in coronary artery disease treatment and prevention.

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