Optimal blood lipid levels counterbalance high polygenic risk of coronary artery disease in 130 000 individuals

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Botta ◽  
A Bolli ◽  
P Di Domenico
Keyword(s):  
Genetic Risk ◽  
Significant Interaction ◽  
Blood Lipids ◽  
Blood Lipid ◽  
Lipid Levels ◽  
High Genetic Risk ◽  
Increased Risk ◽  
Artery Disease ◽  
Cad Risk ◽  
Blood Lipid Levels

Abstract Background Coronary artery disease (CAD) is a complex multifactorial disease leading cause of morbidity and mortality worldwide. Identifying individuals at high risk is crucial to guide life-style and therapeutics interventions. Polygenic Risk Score (PRS) is a weighted sum of common genetic variants that showed to be able to identify a population at greater than threefold risk of CAD compared to the average. Notably, individuals at high genetic risk who adhere to a healthy lifestyle displayed between two and three-fold relative risk reduction, compared to individuals with a poor lifestyle. Despite such evidences, a systematic assessment of the interplay between PRS and CAD risk factors such as blood lipid levels in contributing to the overall CAD risk is still lacking. Methods We analysed in more than 130.0000 individuals of the UK Biobank the association of incident CAD with PRS and blood lipids (LDL, TC, HDL, TC:HDL, LDL:HDL) using a Cox Proportional Hazard Model. We defined three populations: i) Carriers: PRS >95%, Reminders: PRS ≤95% and Reference: PRS ≤95% with optimal blood lipid levels. Carriers and Remainders were stratified by blood lipid levels according to international guidelines. We investigated a potential interaction between blood lipids and PRS and assessed the relative increased risk magnitude in Carriers and Reminders for different blood lipid levels. Results Carriers showed between two and three fold increased risk of incident CAD compared to Reminders at each non-optimal blood lipid level and their ratios. Carriers with LDL between 130 and 160 mg/dL showed higher CAD risk (HR 3.65, 95% CI 2.85–4.63) than Reminders with LDL above 190 mg/dL (HR 2.73, 95% CI 2.18–3.40). Despite that, Carriers displayed non significant increased risk respect to the Reference population for the following blood lipid thresholds: LDL <115 mg/dL, TC <200 mg/dL, HDL >70 mg/dL, LDL:HDL <2.0 and TC:HDL <3.5. The association between LDL cholesterol and CAD was modified by the PRS due to significant interaction (P-value <0.005). The magnitude of increased CAD risk by LDL was higher in Carriers (HR 1.64 95% CI 1.45–1.86 per LDL level) compared to Reminders (HR 1.40, 95% CI 1.34–1.46 per LDL level). Conclusion Using the largest prospective genotyped cohort available to date, we identified for the first time a significant interaction between LDL and genetics in determining CAD incidence. This result have deep implications in a CAD primary prevention perspective. For example individuals with high PRS and borderline-high LDL levels (130–159 mg/dL) are not currently considered to be at elevated risk, despite having higher CAD risk than Remainders with statin-recommended LDL level (>190 mg/dL). Finally, the evidence that optimal lipid levels counterbalance high genetic risk opens new scenarios in the research of targeted risk reduction in the era of precision medicine. Association between PRS and lipid levels Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): EIT Health

scholarly journals Polygenic Risk Score Modifies Risk of Coronary Artery Disease Conferred by Low-Density Lipoprotein Cholesterol

2020 ◽  
Author(s):  
Alessandro Bolli ◽  
Paolo Di Domenico ◽  
Roberta Pastorino ◽  
George Busby ◽  
Giordano Bottà
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Polygenic Risk Score ◽  
Lipid Levels ◽  
Polygenic Risk ◽  
Artery Disease ◽  
Cad Risk ◽  
Blood Lipid Levels

AbstractBackgroundAn individual’s lifetime risk of Coronary Artery Disease (CAD) is determined by a combination of genetic and lifestyle factors. Whilst adherence to a healthy lifestyle can help individuals with high genetic risk reduce their lifetime risk of CAD, the extent to which blood lipid levels affect CAD risk in individuals with varying genetic risk remains unknown. To explore how genetics, blood lipids and CAD risk interact, we derived a novel genome-wide polygenic risk score (PRS) for CAD. We then applied the PRS to individuals from the UK Biobank and divided them into Low PRS (bottom 10 percentiles of PRS distribution), Intermediate PRS (PRS in the 10th-90th percentiles), and High PRS (top 10 percentiles), and further stratified individuals by blood lipid levels.ResultsWe found that the elevated CAD risk conferred by high low-density lipoprotein cholesterol (LDL-C) was modified by the interaction with PRS (P-value interaction: <0.005). Individuals with High PRS and whose LDL-C was Borderline (between 130 and 160 mg/dL) had higher CAD relative risk (HR 3.10; 95% CI, 2.55-3.76) than those at Intermediate PRS whose LDL-C were Very High (>190 mg/dL; HR 2.77; 95% CI, 2.33-3.28). Furthermore, individuals with High PRS but whose lipid levels were below the following thresholds did not have a significantly increased risk for incident CAD: LDL-C <130 mg/dL, total Cholesterol (TC) <200 mg/dL, LDL-C:HDL <2.0 and TC:HDL <3.0. In addition, individuals with Low PRS and Very High LDL-C (>190 mg/dl) did not have increased CAD risk, which was comparable to individuals with Intermediate PRS and Optimal LDL-C (<130 mg/dL).ConclusionsOur results have important implications for the primary prevention of coronary artery disease. Currently, healthy individuals with Borderline LDL-C (130-159 mg/dL) are not considered to be at high risk of CAD. Here we demonstrate that the combination of Borderline LDL-C and High PRS results in CAD relative risk which is greater than individuals without high polygenic risk, but whose LDL-C levels are high enough for statins to be recommended (>190 mg/dL). This analysis therefore demonstrates that PRS can identify a proportion of the population who are at high-risk of CAD but who are invisible to current approaches for assessing CAD risk. Moreover, of perhaps greater significance is the evidence that individuals who have a combination of High PRS and Optimal blood lipid levels do not have greater risk of CAD than individuals without high polygenic risk and the same Optimal blood lipid levels. Our results suggest that high polygenic risk for CAD could be overcome by controlling blood lipid levels. We propose that incorporating PRS into CAD risk assessment early in life could allow individuals at high polygenic risk to benefit from tailored blood lipid guidelines and avoid lifetime exposure to potentially damaging PRS-dependent LDL-C levels.

scholarly journals Characteristics and clinical significance of lipid metabolism in patients with gastrointestinal stromal tumor

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaoling Liu ◽  
Jun Hu ◽  
Bende Liu
Keyword(s):  
Clinical Significance ◽  
Serum Lipids ◽  
Blood Lipids ◽  
High Specificity ◽  
Blood Lipid ◽  
Lipid Levels ◽  
Specificity And Sensitivity ◽  
Union Hospital ◽  
S 100 ◽  
Blood Lipid Levels

Abstract Background To investigate the characteristics and clinical significance of serum lipids in patients with gastrointestinal stromal tumors (GISTs). Methods The clinical and pathological data of 694 GIST patients in Liyuan hospital and Union hospital from 2012 to 2016 were retrospectively analyzed. Blood lipid levels in patients with varying degrees of risk were compared. Results The findings showed that LDL-C, HDL-C, and CHOL increased significantly in women, and CD34 positive. In patients with tumors size less than 5 cm in diameter, TG, HDL-C, and CHOL were significantly higher. TG levels were significantly higher in DOG-1 (a marker and has a high specificity and sensitivity in the diagnosis of GIST) positive patients than in DOG-1 negative patients (P < 0.05). S-100 positive patients had lower HDL-C levels than S-100 negative patients (P < 0.05). Lipids indexes were found to be correlated with GIST risk stratification and tumor site (P < 0.05). TG/HDL-C was were significantly different among patients with GIST in different locations (P < 0.05). Conclusion The clinical and pathological characteristics of the patients with GIST are closely related to the level of blood lipids. To a certain extent, information about level of blood lipids can be helpful for distinguishing benign and malignant GIST.

scholarly journals Evaluation of bi-directional causal association between depression and cardiovascular diseases: a Mendelian randomization study

2020 ◽  
pp. 1-12
Author(s):  
Gloria Hoi-Yee Li ◽  
Ching-Lung Cheung ◽  
Albert Kar-Kin Chung ◽  
Bernard Man-Yung Cheung ◽  
Ian Chi-Kei Wong ◽  
...  
Keyword(s):  
Genetic Predisposition ◽  
Mendelian Randomization ◽  
Secondary Analysis ◽  
Blood Lipid ◽  
Genome Wide Association Studies ◽  
Causal Association ◽  
Lipid Levels ◽  
Increased Risk ◽  
Causal Pathway ◽  
Blood Lipid Levels

Abstract Background Depression and cardiovascular disease (CVD) are associated with each other but their relationship remains unclear. We aim to determine whether genetic predisposition to depression are causally linked to CVD [including coronary artery disease (CAD), myocardial infarction (MI), stroke and atrial fibrillation (AF)]. Methods Using summary statistics from the largest genome-wide association studies (GWAS) or GWAS meta-analysis of depression (primary analysis: n = 500 199), broad depression (help-seeking behavior for problems with nerves, anxiety, tension or depression; secondary analysis: n = 322 580), CAD (n = 184 305), MI (n = 171 875), stroke (n = 446 696) and AF (n = 1 030 836), genetic correlation was tested between two depression phenotypes and CVD [MI, stroke and AF (not CAD as its correlation was previously confirmed)]. Causality was inferred between correlated traits by Mendelian Randomization analyses. Results Both depression phenotypes were genetically correlated with MI (depression: rG = 0.169; p = 9.03 × 10−9; broad depression: rG = 0.123; p = 1 × 10−4) and AF (depression: rG = 0.112; p = 7.80 × 10−6; broad depression: rG = 0.126; p = 3.62 × 10−6). Genetically doubling the odds of depression was causally associated with increased risk of CAD (OR = 1.099; 95% CI 1.031–1.170; p = 0.004) and MI (OR = 1.146; 95% CI 1.070–1.228; p = 1.05 × 10−4). Adjustment for blood lipid levels/smoking status attenuated the causality between depression and CAD/MI. Null causal association was observed for CVD on depression. A similar pattern of results was observed in the secondary analysis for broad depression. Conclusions Genetic predisposition to depression may have positive causal roles on CAD/MI. Genetic susceptibility to self-awareness of mood problems may be a strong causal risk factor of CAD/MI. Blood lipid levels and smoking may potentially mediate the causal pathway. Prevention and early diagnosis of depression are important in the management of CAD/MI.

Comparison of Frame Size and Body Mass Index Methods of Assessment in the Study of Blood Lipids

1992 ◽  
Vol 75 (3) ◽  
pp. 881-882 ◽  
Author(s):  
Thomas Battinelli ◽  
Ray E. Gleason
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Blood Lipids ◽  
Blood Lipid ◽  
Lipid Levels ◽  
Frame Size ◽  
Significant Relationships ◽  
Health Fairs ◽  
Index Methods ◽  
Blood Lipid Levels

This study compared frame size and body mass index methods of assessment in relation to blood lipid levels. The data were obtained from the records of 84 men and 193 women who voluntarily participated in health fairs held at two suburban hospitals. Significant relationships and differences were found between the anthropometric and lipid variables studied. The two methods of classification denoted moderate association and reflected some divergence in classification between them.

scholarly journals Association between maternal serum lipids during late pregnancy and adverse birth outcomes

2020 ◽  
Author(s):  
Meng-Yi Dai ◽  
Lu-Lin Wang ◽  
Yun-Tao Wu ◽  
Huan Li ◽  
Jian-Hong Xia ◽  
...  
Keyword(s):  
Birth Outcomes ◽  
Linear Trend ◽  
Late Pregnancy ◽  
Blood Lipid ◽  
Maternal Blood ◽  
Adverse Birth Outcomes ◽  
Lipid Levels ◽  
Increased Risk ◽  
Unit Increase ◽  
Blood Lipid Levels

Abstract Background: Adverse birth outcomes have short- and long-term impacts on maternal and child health. Maternal dyslipidemia during late pregnancy has been found to be associated with increased risk of adverse birth outcomes. However, similar evidence on association between maternal blood lipid levels and adverse birth outcomes is limited in China.Methods: The data were extracted from Guangdong Women and Children Hospital Information System from September 2014 to March 2018. A total of 3951 mother-newborn pairs were included in our study. Logistic regression model and linear trend analysis were conducted to analyze the correlation between maternal blood lipid levels and adverse birth outcomes after controlling potential confounders including gestational age, pre-pregnancy body mass index, fetal sex, and parity. Results: Among the 3951 subjects, the rates of macrosomia, large-for-gestational age (LGA), low birth weight infants (LBW), and preterm birth were 3.9% (154/3951), 8.5% (334/3951), 9.5% (377/3951), and 9.8% (388/3951), respectively. LDL was a risk factor for preterm birth (OR: 1.20; 95% CI: 1.08-1.34) while HDL was a protective factor (OR: 0.73; 95% CI: 0.55-0.96) after adjusting for covariates. As every unit increase in TG, the risk of macrosomia and LGA increased by 25% (adjusted OR: 1.25; 95% CI: 1.12-1.38) and 16% (adjusted OR: 1.16; 95% CI: 1.07-1.26), respectively. However, every unit increase in HDL concentration was associated with decreased risk for LGA (adjusted OR: 0.60; 95% CI: 0.44-0.81) and macrosomia (adjusted OR: 0.64; 95% CI: 0.41-0.99). High LDL concentrations were associated with a decreased risk of macrosomia (adjusted OR: 0.82; 95% CI: 0.68-0.99) and LGA (adjusted OR: 0.86; 95% CI: 0.76-0.98) but an increased risk of LBW (adjusted OR: 1.16; 95% CI: 1.04-1.30). The results of linear trend analysis were similar to those of logistic regression model.Conclusions: Maternal dyslipidemia during the third trimester is closely related to adverse birth outcomes. Monitoring and managing maternal blood lipid levels in an appropriate range may help to reduce the burden of adverse birth outcomes.

scholarly journals Non-HDL-C Is More Stable Than LDL-C in Assessing the Percent Attainment of Non-fasting Lipid for Coronary Heart Disease Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Li-Ling Guo ◽  
Yan-qiao Chen ◽  
Qiu-zhen Lin ◽  
Feng Tian ◽  
Qun-Yan Xiang ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Statin Therapy ◽  
Blood Lipids ◽  
Blood Lipid ◽  
Lipid Levels ◽  
Short Term ◽  
C Statistic ◽  
Blood Lipid Levels

This study aimed to compare the percentage attainment of fasting and non-fasting LDL-C and non-HDL-C target levels in coronary heart disease (CHD) patients receiving short-term statin therapy. This study enrolled 397 inpatients with CHD. Of these, 197 patients took statins for &lt;1 month (m) or did not take any statin before admission (CHD1 group), while 204 patients took statins for ≥1 m before admission (CHD2 group). Blood lipid levels were measured at 0, 2, and 4 h after a daily breakfast. Non-fasting LDL-C and non-HDL-C levels significantly decreased after a daily meal (P &lt; 0.05). Both fasting and non-fasting LDL-C or non-HDL-C levels were significantly lower in the CHD2 group. The percentage attainment of LDL-C &lt;1.4 mmol/L at 2 and 4 h after a daily breakfast was significantly higher than that during fasting (P &lt; 0.05), but the percent attainment of non-fasting non-HDL-C &lt;2.2 mmol/L was close to its fasting value (P &gt; 0.05). Analysis of c-statistic showed that non-fasting cut-off points for LDL-C and non-HDL-C were 1.19 and 2.11 mmol/L, corresponding to their fasting goal levels of 1.4 and 2.2 mmol/L, respectively. When post-prandial LDL-C and non-HDL-C goal attainments were re-evaluated using non-fasting cut-off points, there were no significant differences in percentage attainment between fasting and non-fasting states. Non-HDL-C is more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. If we want to use LDL-C to assess the percent attainment of post-prandial blood lipids, we may need to determine a lower non-fasting cut-off point.

Soybean Phosphatides and Blood Lipids of Primates1

1979 ◽  
Vol 42 (2) ◽  
pp. 113-119 ◽  
Author(s):  
R. A. ROBBINS ◽  
A. L. BRANEN
Keyword(s):  
Phosphatidyl Choline ◽  
Blood Lipids ◽  
Blood Lipid ◽  
Macaca Nemestrina ◽  
Cholesterol Diet ◽  
Lipid Levels ◽  
Low Fat ◽  
Butter Oil ◽  
Low Fat Diet ◽  
Blood Lipid Levels

Ten pigtail monkeys (Macaca nemestrina) were used to study the effects of soybean phosphatides on blood lipid levels. Two monkeys were maintained on a control low-fat diet and eight monkeys were made hypercholesterolemic by feeding a diet containing 16% butter oil and 1% cholesterol for a 12-week period. Soybean phosphatides were administered to the animals by infusion or incorporation into the diet. All animals were placed on low-fat diets after 12 weeks and maintained on this diet for 5 weeks. Incorporation of 3% soybean phosphatides into the butter oil-cholesterol diet before the animals became hypercholesterolemic or a twice weekly infusion of 5 ml of a 10% emulsion of soybean phosphatides after the animals were hypercholesterolemic partially prevented increases in plasma total cholesterol, cholesterol esters and lipid phosphate induced by the butter oil-cholesterol diets. Alterations in the blood plasma lipoprotein patterns resulting from the butter oil-cholesterol diet were also prevented by these methods of phosphatide administration. Switching the animals to a diet containing phosphatides after the animals were already hypercholesterolemic was not effective in preventing alterations in blood lipid levels or lipoprotein patterns. Blood triglyceride levels were not affected by any of the treatments. The phosphatide treatments had no significant effect on the rate of decrease of blood lipid levels after placing the hypercholesterolemic animals on a low fat-low cholesterol diet. Studies of the turnover of phosphatidyl choline indicate that this phospholipid or its component parts is/are rapidly absorbed and that 10% of the radioactivity of a single oral dose of the phospholipid is released from the tissues of monkeys with a half life of about 2 days. Prior treatment with phosphatides appears to delay excretion of phosphatidyl choline. Possible mechanisms of the action of phosphatides on blood lipids are discussed.

scholarly journals A rare splice donor mutation in the haptoglobin gene associates with blood lipid levels and coronary artery disease

2017 ◽  
Vol 26 (12) ◽  
pp. 2364-2376 ◽  
Author(s):  
Eythor Bjornsson ◽  
Hannes Helgason ◽  
Gisli Halldorsson ◽  
Anna Helgadottir ◽  
Arnaldur Gylfason ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Blood Lipid ◽  
Lipid Levels ◽  
Splice Donor ◽  
Artery Disease ◽  
Haptoglobin Gene ◽  
Blood Lipid Levels

scholarly journals Non-HDL-C is  more stable  than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients

2020 ◽  
Author(s):  
Li-ling Guo ◽  
Yan-qiao Chen ◽  
Qiu-zhen Lin ◽  
Feng Tian ◽  
Li-yuan Zhu ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Statin Therapy ◽  
Blood Lipids ◽  
Blood Lipid ◽  
Lipid Levels ◽  
Short Term ◽  
C Statistic ◽  
Blood Lipid Levels

Abstract Background: This study aimed to compare the percentage attainment of fasting and non-fasting LDL-C and non-HDL-C target levels in coronary heart disease (CHD) patients receiving short-term statin therapy.Methods: This study enrolled 397 inpatients with CHD. Of these, 197 patients took statins for < 1 month (m) or did not take any statin before admission (CHD1 group), while 204 patients took statins for ≥ 1 m before admission (CHD2 group). Blood lipid levels were measured at 0 h, 2 h, and 4 h after a daily breakfast.Results: Non-fasting LDL-C and non-HDL-C levels significantly decreased after a daily meal (P < 0.05). Both fasting and non-fasting LDL-C or non-HDL-C levels were significantly lower in the CHD2 group. The percentage attainment of LDL-C < 1.4 mmol/L at 2 h and 4 h after a daily breakfast was significantly higher than that during fasting (P < 0.05), but the percent attainment of non-fasting non-HDL-C < 2.2 mmol/L was close to its fasting value (P > 0.05). Analysis of c-statistic showed that non-fasting cut-off points for LDL-C and non-HDL-C were 1.19 mmol/L and 2.11 mmol/L, corresponding to their fasting goal levels of 1.4 mmol/L and 2.2 mmol/L, respectively. When postprandial LDL-C and non-HDL-C goal attainments were re-evaluated using non-fasting cut-off points, there were no significant differences in percentage attainment between fasting and non-fasting states.Conclusions: Non-HDL-C is more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. If we want to use LDL-C to assess the percent attainment of postprandial blood lipids, we may need to determine a lower non-fasting cut-off point.

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