Remnant Cholesterol and Ischemic Cardiovascular Disease: A Cross-Sectional Study in Northern China

Background:Heterogeneity exists in the relationship of remnant cholesterol (RC) with cardiovascular disease. In this study, we examined the association between RC and ischemic cardiovascular disease (ICVD) risks and the RC-related risk beyond low-density lipoprotein cholesterol (LDL-C) among people in northern China.Methods:We determined the lipid profile among 65,236 people aged 35–75 years, enrolled between 2015 and 2017, who lived in Inner Mongolia for more than 6 months. Adjusted logistic regression models were used to assess the associations between RC concentration and ICVD risks. Results:In total, 2350 ICVD events were included in the study. RC was significantly associated with the risk of ICVD, CHD events, and ischemic stroke (IS) (ICVD odds ratio [OR] fourth quartile vs first quartile( Q4 vs Q1) 1.253, 95% confidence interval [CI] 1.104–1.421, P trend<0.001; CHD events ORQ4 vs Q1 1.222, 95% CI 1.018–1.466, P trend=0.034; IS ORQ4 vs Q1 1.288, 95% CI 1.090–1.522, P trend=0.001). This association remained significant after including LDL-C and high-density lipoprotein cholesterol (HDL-C). Moreover, the discordant high RC/low LDL-C groupwas associated with increased ICVD risk compared with the low RC/low LDL-C group (OR 1.174, 95% CI 1.029–1.339). Similar results were obtained when adjusting for traditional risk factors of ICVD. Conclusions: We found that RC was associated with an increased risk of ICVD independent of traditional risk factors, LDL-C, and HDL-C levels. The interaction of RC and LDL-C was associated with the risk of ICVD risks.

Relationship between Serum Angiopoietin-like Proteins 3 and 8 and Atherogenic Lipid Biomarkers in Non-Diabetic Adults Depends on Gender and Obesity

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25–74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.

Remnant cholesterol is an independent determinant of the presence and extent of subclinical carotid atherosclerosis in statin-naive individuals

Background Despite continuous improvements of diagnostic and therapeutic algorithms for cardiovascular disease (CVD), mortality from CVD remains high suggesting unaddressed residual risk. Remnant cholesterol (RC) consists the cholesterol content of triglyceride-rich lipoproteins, which along with LDL cholesterol infiltrate the arterial wall, accumulate and cause atherosclerosis. Increased remnant cholesterol (RC) levels have been previously associated with future adverse cardiac events despite hypolipidemic therapy. However, a mechanistic association of RC levels with human atherosclerosis in vivo has not been proven in a clinical setting. Purpose To evaluate the association of RC levels with the presence and extend of subclinical carotid atherosclerosis. Methods In this retrospective cohort study, 438 subjects from the Athens Vascular Registry without clinically overt CVD or treatment with statin were recruited. Atherosclerotic burden was assessed by B-mode carotid ultrasonography using: 1. Maximal carotid wall thickness [maxWT, the highest intima-media thickness (IMT) or highest atherosclerotic plaque thickness (PLQ) if present derived from all carotid sites], 2. Total thickness (sumWT, sum of maximal wall thickness), 3) high plaque burden (PLQ ≥2) and 4) average carotid IMT (avgIMT). RC was calculated using the formula RC=total cholesterol-LDL-C-HDL-C. Results Mean (SD) age was 54.8±12.4 years old with 41% being males. Subjects with RC&gt;median (=18mg/dl) had higher sumWT (6.12±0.7 vs 5.57±1.7, p=0.002), maxWT (1.61±0.7 vs 1.43±0.7, p=0.008) and avgIMT (0.88±0.16 vs 0.83±0.16, p=0.003) vs RC&lt;median.&gt;median was associated with higher odds for increased sumWT (highest tertile, OR: 2.15 95% CI 1.26–3.66, p=0.006) and maxWT (OR: 2.15 95% CI: 1.38–3.33, p=0.001), and a higher plaque burden (≥2 plaques, OR: 2.1 95% CI 1.93–3.1, p&lt;0.001) after adjustment for age, gender and systolic blood pressure, glomerular filtration rate, smoking, diabetes mellitus, body mass index and LDL-C Conclusion In a statin-naive population without clinically overt CVD, increased RC levels were associated with the presence and extend of subclinical carotid atherosclerosis. These findings provide novel mechanistic insight into mechanisms associated with increased CVD risk in individuals with high RC levels. FUNDunding Acknowledgement Type of funding sources: None.

Lipid profile in cardiac transplantation: a closer look at bad cholesterol

Background When it comes to lipid-lowering therapy, the primary goal is still to reduce the low-density lipoprotein levels. Although remnant cholesterol (RC), including predominantly intermediate- and very-low-density lipoproteins, is a known cardiovascular risk factor, reliable reference values, as well as therapy strategies, are yet to be validated. Additionally, the role of RC after heart transplantation is still unclear. Aim To assess the clinical and prognostic relevance of lipid profile and, in particular, of remnant cholesterol in very long-term follow-up after HTx. Methods We performed a retrospective analysis of the clinical and laboratory parameters collected at last follow-up in an outpatient setting. Additionally, remnant cholesterol levels were estimated using the formula (in mg/dL): remnant cholesterol = total cholesterol – (HLD-C + LDL-C). Results Out of 174 patients with a mean age of 45.2±15.0 years at the time of HTx and a mean follow-up of 13.1±6.5 years, 142 (81.6%) were on statin treatment. Mean cholesterol level was borderline high (184.1±48.4 mg/dL), whereas mean LDL and triglyceride values were markedly elevated (103.6±39.2 and 161.8±83.8 mg/dL, respectively). HDL results were found to be 57.1±17.5 mg/dL. Statin treatment was associated with significantly lower LDL levels (124.6±53.5 vs. 98.8±33.6 mg/dL on statins, p=0.013), but failed to show prognostic relevance in a univariate cox-regression analysis (HR 0.79, 95% CI 0.37 – 1.72, p=0.57). RC was elevated in comparison to the background population with a mean level of 23.5±17.3 mg/dL (24.2±18.1 in male and 21.3±14.8 mg/dL in female) and a tendency for lower values when on treatment with statins but without statistical significance (28.5±19.2 vs. 22.3±16.8 mg/dL on statins, p=0.07). Treatment with higher doses of statins showed no relevant influence on the RC levels (p=0.62). Additionally, elevated RC was associated with higher C-reactive protein values as a sign of systemic inflammation (CRP &gt;0.5 mg/dL, OR 1.1, 95% CI 1.007 – 1.046, p=0.007). In a multivariate cox-regression analysis (adjusted for total cholesterol, LDL and triglycerides) RC was identified as a significant factor influencing mortality (HR 1.11, 95% CI 1.05 – 1.17, p&lt;0.001). Conclusions When addressing dyslipidaemia in heart transplantation, statin therapy can help reduce LDL levels, but this approach seems to be insufficient in achieving clinical benefit. Remnant cholesterol is a factor, which has proinflammatory properties and can potentially influence the prognosis in HTx. The possible therapeutic alternatives for this overseen component of the lipid profile are yet to be elucidated. FUNDunding Acknowledgement Type of funding sources: None.

Maternal lipid profile in pregnancy and embryonic growth: a population-based prospective cohort study.

Objective To investigate the association between the maternal lipid profile in early pregnancy and embryonic growth. Design Prospective population-based cohort study. Setting Rotterdam, the Netherlands. Population We included 1474 women from the Generation R(otterdam) Study. Methods The maternal lipid profile was defined as total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), remnant cholesterol, non-high-density (non-HDL-c) lipoprotein cholesterol concentrations and the triglycerides/high-density lipoprotein (TG/HDL-c) ratio. Additionally, maternal glucose concentrations were assessed. Associations were studied with linear regression models, adjusted for confounding factors: maternal age, pre-pregnancy BMI, parity, educational level, ethnicity, smoking and folic acid supplement use Main Outcome Measures Crown-rump length (CRL). Results Triglycerides and remnant cholesterol concentrations are positively associated with embryonic growth (fully adjusted models, 0.17 SDS: 95% CI 0.03 ; 0.30, and 0.17 SDS: 95% CI 0.04 ; 0.31, respectively). These associations were not present in women with normal weight (triglycerides and remnant cholesterol: fully adjusted model, 0.44 SDS: 95% CI 0.15 ; 0.72). Associations between maternal lipid concentrations and embryonic growth were not attenuated after adjustment for glucose concentrations. Total cholesterol, HDL-c, LDL-c, non-HDL-c concentrations and the TG/HDL-c ratio were not associated with embryonic growth. Conclusions Higher triglycerides and remnant cholesterol concentrations in early pregnancy are associated with increased embryonic growth, most notably in overweight women. Keywords Pregnancy, Cholesterol, Low-density lipoprotein (LDL-c), High-density lipoprotein (HDL-c), Triglycerides, Intrauterine development, Fetal growth, Early pregnancy Tweetable abstract The maternal lipid profile in pregnancy is associated with embryonic growth.

Determination of the Optimal Cutoff Value of Triglyceride That Corresponds to Fasting Levels in Chinese Subjects With Marked Hypertriglyceridemia

The level of triglyceride (TG) ≥ 2. 3 mmol/L is suggestive of marked hypertriglyceridemia (HTG) and requires treatment with a triglyceride-lowering agent in high-risk and very high-risk patients as recommended by the 2019 ESC/EAS guidelines for the management of dyslipidemia. However, the optimal cutoff value required to diagnose non-fasting HTG that corresponds to the fasting goal level of 2.3 mmol/L in Chinese subjects is unknown. This study enrolled 602 cardiology inpatients. Blood lipid levels, including calculated non-high-density lipoprotein cholesterol (non-HDL-C) and remnant cholesterol (RC), were measured at 0, 2, and 4 h after a daily Chinese breakfast. Of these, 482 inpatients had TG levels of &lt;2.3 mmol/L (CON group) and 120 inpatients had TG levels of ≥2.3 mmol/L (HTG group). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff values for postprandial HTG that corresponded to a target fasting level of 2.3 mmol/L. Marked hypertriglyceridemia (≥2.3 mmol/L) was found in 120 (19.9%) patients in this study population. The levels of non-fasting TG and RC increased significantly in both groups and reached the peak at 4 h after a daily meal, especially in the HTG group (p &lt; 0.05). The optimal cutoff value of TG at 4 h, which corresponds to fasting TG of ≥2.3 mmol/L, that can be used to predict HTG, was 2.66 mmol/L. According to the new non-fasting cutoff value, the incidence of non-fasting HTG is close to its fasting level. In summary, this is the first study to determine the non-fasting cutoff value that corresponds to a fasting TG of ≥2.3 mmol/L in Chinese patients. Additionally, 2.66 mmol/l at 4 h after a daily meal could be an appropriate cutoff value that can be used to detect non-fasting marked HTG in Chinese subjects.