Nonfasting Remnant Cholesterol Research Articles

Nonfasting remnant cholesterol and cardiovascular disease risk prediction in Albertans: a prospective cohort study.

European studies have shown that nonfasting remnant cholesterol can be a strong predictor of cardiovascular disease risk and may contribute to identifying residual risk; however, Canadian data are lacking on nonfasting remnant cholesterol. In this study, we aimed to determine the relation between nonfasting remnant cholesterol, low-density lipoprotein (LDL) cholesterol and cardiovascular disease among people in Alberta. In this retrospective analysis, we used data from Alberta's Tomorrow Project, a large prospective cohort that enrolled Albertans aged 35-69 years (2000-2015). Participants with consent to data linkage, with complete nonfasting lipid data and without existing cardiovascular disease were included. The nonfasting remnant cholesterol and LDL cholesterol relation with a composite cardiovascular disease outcome of major incident cardiovascular diagnoses, ascertained by linking to Alberta Health databases, was determined by multivariable logistic regression, adjusting for age, sex, statin use, comorbidities, and LDL cholesterol or remnant cholesterol. The final sample of 13 988 participants was 69.4% female, and the mean age was 61.8 (standard deviation [SD] 9.7) years. Follow-up time was approximately 15 years. Mean remnant cholesterol was significantly higher among individuals with versus without cardiovascular disease (0.87 [SD 0.40] mmol/L v. 0.78 [SD 0.38] mmol/L, standardized mean difference [SMD] -0.24), and mean LDL cholesterol was significantly lower (2.69 [SD 0.93] mmol/L v. 2.88 [SD 0.84] mmol/L, SMD 0.21). The odds of incident composite cardiovascular disease were significantly increased per mmol/L increase in remnant cholesterol (adjusted odds ratio [OR] 1.48, 95% confidence interval [CI] 1.27-1.73) but significantly decreased per mmol/L increase in LDL cholesterol (adjusted OR 0.73, 95% CI 0.68-0.79). In this large Albertan cohort of predominantly older females, nonfasting remnant cholesterol had a positive relation with cardiovascular disease incidence, whereas LDL cholesterol did not. These findings support the clinical utility of measuring non-fasting remnant cholesterol to detect cardiovascular disease risk.

Non-fasting lipids and cardiovascular disease in those with and without diabetes in Alberta's Tomorrow Project: a prospective cohort study.

Non-fasting remnant cholesterol (RC) is a novel marker of cardiovascular disease (CVD) risk, however data on this relationship in Canadians with diabetes (at high risk of CVD) is lacking. The objective of this analysis was to determine the relationship of RC with CVD in individuals with and without diabetes in the Alberta's Tomorrow Project (ATP) cohort. Non-fasting lipid data collected as part of the ATP was linked to administrative health records (October 2000 - March 2015) to ascertain incident CVD and prevalent diabetes. Participants without prevalent CVD or incident diabetes and who had complete, non-negative non-fasting lipid data collected with triglycerides <4.5mmol/L were included (n=13,631). The relationship between non-fasting RC and incident CVD diagnoses was assessed by Cox proportional hazards regression, after stratification by diabetes status. Participants were 69.8% women with a mean age of 61.6±9.7 years, and 6.5% had prevalent diabetes. Non-fasting RC was higher in participants with diabetes compared to those without (mean 0.94±0.41mmol/L vs. 0.77±0.38mmol/L, p<0.0001) and was associated with increased risk of incident CVD among those without diabetes (adjusted hazard ratio (aHR) 1.22, 95% CI 1.03-1.43, p=0.02). Although a similar trend was observed in participants with diabetes it did not reach statistical significance (aHR 1.31, 95% CI 0.84-2.05, p=0.23). Elevated non-fasting RC predicted increased CVD risk in middle and older-aged adults without diabetes; similar trends were observed in participants with diabetes and requires further testing in a larger sample.

Comparative Study of Remnant Cholesterol, Some Lipid Fractions and FBS Level in Overweight and Obese Participants in South East Nigeria

Background: Obesity is one of the characteristics of metabolic disorders, it has been linked to cardiovascular diseases. Remnant cholesterol has been proposed to be a link between obesity and coronary heart disease, thus a risk factor for the development of cardiovascular disease in obese people. We compared the level of calculated non-fasting remnant cholesterol, fasting and non-fasting lipid profile and fasting blood sugar in overweight, obese and normal weight participants in Nnewi, a town in South East Nigeria.&#x0D; Methods: In this cross-sectional study, a total of 90 apparently healthy obese, overweight and normal weight participants who met the inclusion criteria were randomly enrolled. They were grouped using their body mass index of 18.5 to 24.9 kg/m2 (normal weight), 25 to 29.9 kg/m2 (overweight) and ≥30 kg/m2 (obese). The parameters were analyzed using standard methods.&#x0D; Results: Our results shows that there was progressive increase of remnant cholesterol among the group, this increase has no statistical difference (p&gt;0.05) in the mean calculated remnant cholesterol (mmol/l) between the obese (0.72±0.4), overweight (0.68±0.46), and normal weight (0.50±0.28) participants. The mean fasting Very Low Density Lipoprotein (VLDL) and Triglyceride (TG) (mmol/l) were significantly higher (p&lt;0.05) in overweight compared to normal weight participants (0.76±0.31 vs. 0.47±0.22) and (1.72±0.60 vs. 1.09±0.51) and obese participants (0.82±0.23 vs. 0.47±0.22) and (1.85±0.59 vs. 1.09±0.51) when compared to normal weight participants respectively. FBS levels (mmol/l) were significantly lower in normal weight participants when compared to overweight participants (3.45±0.79 vs. 4.46±1.82) and obese participants (3.46± 0.79 vs. 4.94±1.26).&#x0D; Conclusion: The results obtained from this study demonstrated a progressive increase in the level of remnant cholesterol which was not statistically significant among apparently healthy individuals across the group. Furthermore we did not observed Remnant cholesterol as a sole predictor to obesity which will lead to cardiovascular diseases, with the rising prevalence of obesity in developing country as well as its associated complications and risks.

Cholesterol Remnants, Triglyceride-Rich Lipoproteins and Cardiovascular Risk.

Randomized clinical trials with statins and other lipid-lowering drugs have shown the presence of a "residual cardiovascular risk" in those treated to "target" for LDL-cholesterol. This risk is mainly associated to lipid components other than LDL and in particular to remnant cholesterol (RC) and to lipoproteins rich in triglycerides in fasting and non-fasting conditions. During fasting, RCs correspond to the cholesterol content of the VLDL and their partially depleted triglyceride remnant containing apoB-100. Conversely, in non-fasting conditions, RCs include also cholesterol present in chylomicrons containing apoB-48. Therefore, RCs refer to total plasma cholesterol minus HDL-cholesterol and LDL-cholesterol, that is, all the cholesterol present in the VLDL, chylomicrons and in their remnants. A large body of experimental and clinical data suggests a major role of RCs in the development of atherosclerosis. In fact, RCs easily pass the arterial wall and bind to the connective matrix stimulating the progression of smooth muscle cells and the proliferation of resident macrophages. RCs are a causal risk factor for cardiovascular events. Fasting and non-fasting RCs are equivalent for predicting vascular events. Further studies on drugs effect on RC levels and clinical trials to evaluate the efficacy of RC reduction on cardiovascular events are needed.

Remnant cholesterol is prospectively associated with cardiovascular disease events and all-cause mortality in kidney transplant recipients: the FAVORIT study.

The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of cardiovascular disease (CVD) outcomes, all-cause mortality or transplant failure in kidney transplant recipients (KTRs). Our primary aim was to investigate the prospective association of remnant cholesterol and the risk of CVD events in renal transplant recipients with secondary aims evaluating remnant cholesterol and renal graft failure and all-cause mortality among participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial. Among 4110 enrolled participants, 98 were excluded for missing baseline remnant cholesterol levels and covariates. Nonfasting remnant cholesterol levels were calculated based on the lipid profiles in 3812 FAVORIT trial participants at randomization. A Wilcoxon-type test for trend was used to compare baseline characteristics across remnant cholesterol quartiles. Cox proportional hazards regression was used to evaluate the association of baseline remnant cholesterol levels with time to primary and secondary study outcomes. During a median follow-up of 4.0 years we documented 548 CVD incident events, 343 transplant failures and 452 all-cause deaths. When comparing the highest quartile (quartile 4) to quartile 1, proportional hazard modeling revealed a significant increase in CVD risk {hazard ratio [HR] 1.32 [95% confidence interval (CI) 1.04-1.67]} and all-cause mortality risk [HR 1.34 (95% CI 1.01-1.69)]. A nonsignificant increase in transplant failure was seen as well [HR 1.20 (95% CI 0.87-1.64)]. Remnant cholesterol is associated with CVD and all-cause mortality in long-term KTRs. A randomized controlled clinical trial in KTRs that assesses the potential impact of remnant cholesterol-lowering therapy on these outcomes may be warranted.

Contribution of remnant cholesterol to cardiovascular risk.

Remnant cholesterol in triglyceride-rich lipoproteins is associated observationally and genetic, causally with increased risk of atherosclerotic cardiovascular disease in healthy individuals. We tested the hypothesis that an unmet medical need exists in individuals with high nonfasting remnant cholesterol and prior atherosclerotic cardiovascular disease. From amongst 109574 individuals in a prospective cohort study of the Danish general population, we included 2973 individuals aged 20-80 with baseline diagnoses of myocardial infarction/ischaemic stroke ascertained from national Danish health registries. The recurrent major cardiovascular event (MACE) incidence rates per 1000 person-years were 39 (95% confidence interval: 30-50) for individuals with remnant cholesterol levels≥1.5 mmol L-1 (≥58 mg dL-1 ), 31 (26-37) for 1-1.49 mmol L-1 (39-57 mg dL-1 ), 27 (24-31) for 0.5-0.99 mmol L-1 (19-38 mg dL-1 ) and 23 (19-27) for individuals with remnant cholesterol<0.5 mmol L-1 (<19 mg dL-1 ). Compared to individuals with remnant cholesterol<0.5 mmol L-1 (<19 mg dL-1 ), the subhazard ratio for recurrent MACE was 1.23 (95%CI:0.98-1.55) for individuals with remnant cholesterol levels of 0.5-0.99 mmol L-1 (19-38 mg dL-1 ), 1.48 (1.14-1.92) for 1-1.49 mmol L-1 (39-57 mg dL-1 ) and 1.79 (1.28-2.49) for≥1.5 mmol L-1 (≥58 mg dL-1 ). The recurrent MACE incidence rates per 1000 person-years for individuals with remnant cholesterol levels<0.5mmol L-1 (<19 mg dL-1 ) and≥1.5 mmol L-1 (≥58 mg dL-1 ) were 10 (6.6-15) and 31 (21-47) for those below age 65 and correspondingly 25 (21-30) and 43 (32-59) for those with LDL cholesterol levels<3mmol L-1 (<116 mg dL-1 ), respectively. For a 20% recurrent MACE risk reduction in secondary prevention, an estimated remnant cholesterol lowering of 0.83 mmol L-1 (32mg dL-1 ) would be needed. In individuals with a diagnosis of myocardial infarction/ischaemic stroke, a lower remnant cholesterol of 0.8 mmol L-1 (32 mg dL-1 ) was estimated to reduce recurrent MACE by 20% in secondary prevention. Our data indicate an unmet medical need for secondary prevention in individuals with high nonfasting remnant cholesterol levels.

Comparison of remnant cholesterol levels estimated by calculated and measured LDL-C levels in Chinese patients with coronary heart disease

BackgroundEvidence about whether remnant cholesterol (RC), especially non-fasting RC, is a causal risk factor for coronary heart disease (CHD) in Chinese subjects is rare. Recently, estimated RC level (RCe) was applied in many studies with large population. We aimed to compare fasting and non-fasting RCe calculated by LDL-C level determined by different methods in Chinese subjects, and investigate their contributions to CHD. MethodsLevels of TC, TG and HDL-C were measured directly in 273 CHD patients (CHD group) and 136 controls (CON group) before and at 4 h after a daily breakfast. LDL-C level was measured directly or calculated by Friedewald equation at TG < 4.5 mmol/L. RC level estimated by calculated or measured LDL-C was termed as RCe1 or RCe2. Contributions of different RC levels to CHD were evaluated by multivariable logistic regression analysis. ResultsBoth RCe1 and RCe2 increased significantly at 4 h after breakfast (both p < 0.05). RCe1 was significantly higher than RCe2 in fasting or non-fasting state (p < 0.05). RCe1 was closely related to RCe2, especially in the highest quartile of RCe1 (p < 0.05). Non-fasting RCe1 or RCe2 and fasting RCe2 independently predicted CHD after adjustment for traditional risk factors (all p < 0.05). ConclusionsAlthough RCe1 was significantly higher than RCe2, non-fasting RCe, no matter RCe1 or RCe2, after a daily breakfast was an independent predictor for CHD risk in Chinese subjects, indicating that the non-fasting state is critical in the development of atherosclerosis.

Artmış Kalıntı Kolesterol Kan Düzeyleri İlk Defa Geçirilen Akut Koroner Sendrom ile İlişkilidir

Introduction: This study aimed to investigate the association between remnant cholesterol and acute coronary syndrome (ACS) and its predictive value for acute coronary syndrome occurring for the first time. Patients and Methods: We compared increasing concentrations of non-fasting remnant cholesterol aside from other lipid profile parameters to investigate this association in 226 patients with ACS for the first time and 192 elective coronary angiography patients with normal coronary arteries. Results: Patients with ACS were mostly males and were younger than those in the control group; moreover, they had higher percentage of diabetes mellitus (for all p< 0.001). Glucose and white blood cell levels at admission were also higher in patients with ACS. Remnant cholesterol level (such as LDL-C) was statistically higher in the ACS group compared with those of the control group (p< 0.001). In the univariate and bivariate binary logistic regression analysis, high blood remnant cholesterol, high blood LDL-C, and low blood HDL-C levels had a predictive value for ACSs. Conclusion: This study demonstrated that remnant cholesterol levels (such as high blood LDL-C levels) are associated with increased risk of ACS for the first time. Further studies should be performed focusing on lowering remnant cholesterol levels apart from lowering LDL-C levels in patients with ACS.

The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Nonfasting Remnant Cholesterol in a Real World Population.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated significant effects on low-density lipoprotein (LDL) cholesterol and nonhigh density lipoprotein (HDL) cholesterol. To date, there have been limited reports on the effect of PCSK9 inhibitors on remnant cholesterol. Objectives Assess the effect of PCSK9 inhibitors on nonfasting remnant cholesterol in a real world population. Identify whether pretreatment triglyceride levels are associated with PCSK9 inhibition success as indicated by changes in remnant cholesterol levels. Methods Patients in our adult lipid clinic (n = 109) receiving PCSK9 inhibition for atherosclerotic cardiovascular disease or familial hypercholesterolemia who had available pre- and post-PCSK9 inhibition standard nonfasting lipid data were, retrospectively, selected for data analysis. Remnant cholesterol was the difference between non-HDL and LDL cholesterol. LDL cholesterol was measured directly and calculated from Friedewald and Martin/Hopkins methods. Data were analyzed using repeated measures ANOVA and multivariable linear regression for differential effects on remnant and LDL cholesterol based upon pretreatment nonfasting triglyceride levels. Results Remnant cholesterol as well as total, LDL, non-HDL cholesterol, and triglycerides decreased significantly (P<0.001) after PCSK9 inhibition. Patients with higher pretreatment triglyceride levels showed greater decrease in remnant cholesterol after PCSK9 inhibition (P<0.001) than those with lower pretreatment triglycerides. Conclusions In patients receiving PCSK9 inhibitors, remnant cholesterol as determined from nonfasting blood was reduced in proportion to pretreatment triglycerides.

Predictive value of non-fasting remnant cholesterol for short-term outcome of diabetics with new-onset stable coronary artery disease

BackgroundThe relationship between non-fasting remnant cholesterol and cardiovascular outcome in the era of potent statin therapy remained to be elucidated.MethodsA cohort study of three hundred and twenty eight diabetics diagnosed with new-onset stable coronary artery disease (CAD) by coronary angiography were enrolled. All cases were followed up for an average duration of twelve months. The association between baseline remnant cholesterol levels and major cardiovascular outcomes were evaluated using the receivers operating characteristic (ROC) curves and Cox proportional hazards regression analysis.ResultsDuring a period of 12-month’s follow-up, 14.3% patients (47/328) underwent pre-specified adverse outcomes. The remnant cholesterol associated with high sensitivity C-reactive protein, neutrophil count and fibrinogen (R2 = 0.20, 0.12 and 0.14; P = 0.000, 0.036 and 0.010 respectively). Area under the ROC curves (AUC) indicated discriminatory power of the remnant cholesterol to predict the adverse outcomes for this population (AUC = 0.64, P < 0.005). Kaplan-Meier curve suggested that the lower levels of remnant cholesterol showed relatively lower cardiac events for diabetic patients with stable CAD (Log rank X2 = 8.94, P = 0.04). However, according to multivariate Cox proportional hazards regression, apart from hemoglobin A1C (Hazard ratio [H.R.] =1.38, 95% CI: 1.14–1.66, P = 0.001) and Gensini scores (H.R. = 1.00, 95% CI: 1.00–1.02; P = 0.035), remnant cholesterol did not qualify as an independent predictor of adverse prognosis in these settings (H.R. = 1.05, 95% CI: 0.46–2.37, P = 0.909).ConclusionsNon-fasting remnant cholesterol was associated with inflammatory biomarkers and high incidence of revascularization, but not qualified as an independent predictor for short-term prognosis of diabetics with new-onset stable coronary artery disease.

Commentary: Nonfasting remnant cholesterol simplifies triglyceride-rich lipoproteins for clinical use, and metabolomic phenotyping ignites scientific curiosity.

Commentary: Nonfasting remnant cholesterol simplifies triglyceride-rich lipoproteins for clinical use, and metabolomic phenotyping ignites scientific curiosity.

Extreme nonfasting remnant cholesterol versus extreme low-density lipoprotein cholesterol as contributors of cardiovascular disease and all-cause mortality in 90,000 individuals from the general population

Aims: Elevated concentrations of nonfasting remnant cholesterol like elevated low-density lipoprotein(LDL) cholesterol concentrations are causally associated with increased risk of ischemic heart disease(IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors of risk of IHD, myocardial infarction(MI), and all-cause mortality, which is presently unknown.

Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population.

Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality. We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died. Compared with participants with nonfasting remnant cholesterol <0.5 mmol/L (19.3 mg/dL), hazard ratios for IHD ranged from 1.3 (95% CI 1.1-1.5) for remnant cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2.4 (1.9-2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend <0.001). Compared with participants with LDL cholesterol <3.0 mmol/L (115.8 mg/dL), hazard ratios for IHD ranged from 1.3 (1.1-1.5) for LDL cholesterol of 3-3.99 mmol/L (115.8-154 mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P < 0.001). Corresponding hazard ratios for MI ranged from 1.8 (1.4-2.3) to 3.4 (2.5-4.8) for remnant cholesterol (P < 0.001), and from 1.7 (1.4-2.2) to 4.7 (3.5-6.3) for LDL cholesterol (P < 0.001). Nonfasting remnant cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9-1.1) to 1.6 (1.4-1.9) (P < 0.001), whereas LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7-0.8) to 0.9 (0.8-1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality. Both lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk.

Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss.

Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study.

Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with high cardiovascular risk. This may be because that low 25(OH)D levels are associated with high levels of atherogenic lipoproteins, but whether these 2 risk factors are genetically associated is unknown. We tested this hypothesis. Using a Mendelian randomization approach, potential genetic associations between plasma levels of atherogenic lipoproteins and 25(OH)D were examined in ≤85,868 white, Danish individuals in whom we genotyped for variants affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol levels was observationally associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not associate genetically with levels of remnant and low-density lipoprotein-cholesterol. Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH)D levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.

Simvastatin and ezetimibe have opposing regulation on intestinal cholesterol absorption and trans intestinal cholesterol excretion (tice) during metabolic syndrome

Objectives: Recent results from the Copenhagen Heart Study have demonstrated a role for non-fasting remnant cholesterol as a causal risk factor for cardiovascular disease (CVD). Evidence in humans, rats and hamsters also show that insulin resistance stimulates overproduction of intestinal derived remnant lipoproteins and may further exacerbate CVD risk. We have recently demonstrated that statins can increase intestinal remnant cholesterol in a rat model of the Metabolic Syndrome (MetS). Here we proposed to evaluate the impact of combining simvastatin (SV) with an intestinal cholesterol absorption inhibitor (ezetimibe [EZ]) on intestinal cholesterol secretion and/or Trans Intestinal Cholesterol Excretion (TICE) in a rodent model of MetS.

Select Articles Published on the Topic of Coronary Heart Disease in 2013

Select Articles Published on the Topic of Coronary Heart Disease in 2013

Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown. We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by CRP alleles, and C-reactive protein by IL6R alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35-39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10-48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6-7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1-5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5-2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity. Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation.

Remnant Cholesterol as a Causal Risk Factor for Ischemic Heart Disease

The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol. Elevated remnant cholesterol is associated with elevated levels of triglyceride-rich lipoproteins and with reduced HDL cholesterol, and all are associated with ischemic heart disease. A total of 73,513 subjects from Copenhagen were genotyped, of whom 11,984 had ischemic heart disease diagnosed between 1976 and 2010. Fifteen genetic variants were selected, affecting: 1) nonfasting remnant cholesterol alone; 2) nonfasting remnant cholesterol and HDL cholesterol combined; 3) HDL cholesterol alone; or 4) low-density lipoprotein (LDL) cholesterol alone as a positive control. The variants were used in a Mendelian randomization design. The causal odds ratio for a 1 mmol/l (39 mg/dl) genetic increase of nonfasting remnant cholesterol was 2.8 (95% confidence interval [CI]: 1.9 to 4.2), with a corresponding observational hazard ratio of 1.4 (95% CI: 1.3 to 1.5). For the ratio of nonfasting remnant cholesterol to HDL cholesterol, corresponding values were 2.9 (95% CI: 1.9 to 4.6) causal and 1.2 (95% CI 1.2 to 1.3) observational for a 1-U increase. However, for HDL cholesterol, corresponding values were 0.7 (95% CI: 0.4 to 1.4) causal and 1.6 (95% CI: 1.4 to 1.7) observational for a 1 mmol/l (39 mg/dl) decrease. Finally, for LDL cholesterol, corresponding values were 1.5 (95% CI: 1.3 to 1.6) causal and 1.1 (95% CI: 1.1 to 1.2) observational for a 1 mmol/l (39 mg/dl) increase. A nonfasting remnant cholesterol increase of 1 mmol/l (39 mg/dl) is associated with a 2.8-fold causal risk for ischemic heart disease, independent of reduced HDL cholesterol. This implies that elevated cholesterol content of triglyceride-rich lipoprotein particles causes ischemic heart disease. However, because pleiotropic effects of the genetic variants studied cannot be totally excluded, these findings need to be confirmed using additional genetic variants and/or randomized intervention trials.