Baseline apoB Research Articles

Nomogram for predicting the prognosis of metastatic colorectal cancer patients treated with anti-PD1 therapy based on serum lipids analysis.

Serum lipids have been identified to be used as prognostic biomarkers in several types of cancer. The primary objective of this study was to evaluate the prognostic value of serum lipids in metastatic colorectal cancer (mCRC) patients received anti-PD-1 therapy. Pretreatment and the alteration of serum lipids, including apolipoprotein B (ApoB), apolipoprotein A-I (ApoA-I), cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) after 2 courses of anti-PD1 therapy, were collected. Kaplan-Meier survival and cox regression analysis were performed to identify the prognostic values on overall survival (OS). Finally, those significant predictors from multivariate analysis were used to construct a nomogram for the prediction of prognosis. Baseline ApoB, CHO, HDL-C, LDL-C and early changes of ApoB, ApoA-I, HDL-C were statistically significant in the ROC analysis, showing good discriminatory ability in terms of OS. In multivariate analysis, treatment lines, lung metastasis, baseline HDL-C (low vs. high, HR, 6.30; 95% CI 1.82-21.80; P = 0.004) and early changes in HDL-C (reduction vs. elevation, HR, 4.59, 95% CI 1.20-17.63; P = 0.026) independently predicted OS. The area under the time-dependent ROC curve at 1 year, 2 years and 3 years consistently demonstrated the satisfactory accuracy and predictive value of the nomogram (AUC: 0.88, 0.85, 0.84). Overall, high level at baseline and an early elevation of HDL-C are correlated with better outcomes in mCRC patients treated with anti-PD1 therapy. The constructed nomogram indicated that the factors are strong predictive markers for response and prognosis to anti-PD-1 therapy in metastatic colorectal cancer.

Apolipoprotein B is associated with CT-angiographic progression beyond low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol in patients with coronary artery disease

BackgroundAccumulating evidence indicated that apolipoprotein B (apoB) was the principal lipid determinant of coronary artery disease (CAD). Nevertheless, the connection between apoB and angiographic progression of CAD remained undetermined.MethodsFive hundred and forty-four CAD patients with twice coronary computed tomography angiography experiences were enrolled. The Gensini scoring system was used to assess angiographic progression. Incident angiographic progression was defined as an annual change rate of the Gensini score of > 1 point. The predictive efficacy of baseline apoB levels for angiographic progression was assessed using a receiver operating characteristic (ROC) curve. For comparative purposes, patients were categorized into three groups according to their baseline apoB tertiles. Furthermore, discordance analyses defined by the median were performed to assess the superiority of apoB over lipoprotein cholesterol in predicting angiographic progression of CAD.ResultsAngiographic progression was observed in 184 patients (33.8%) during a follow-up period of 2.2-year. The area under the ROC curve was 0.565 (0.522–0.607, P = 0.013). The incidence of angiographic progression was elevated with increasing apoB tertile after adjusting for confounding factors [odds ratio (OR) for the medium apoB tertile: 1.92, 95% confidence interval (CI): 1.15–3.19, P = 0.012; OR for the high apoB tertile: 2.05, 95%CI:1.17–3.60, P = 0.013]. Additionally, discordance analyses showed that the higher apoB group had a significantly higher risk of CAD progression in the fully adjusted model (all P < 0.05).ConclusionsApoB could be used as an accurate and comprehensive indicator of angiographic progression in patients with CAD.

The association of apolipoprotein B with chronic kidney disease in the Chinese population.

Whether serum apolipoprotein B (ApoB) is a risk factor for the development of Chronic kidney disease (CKD) has not been fully established in the general population. Therefore, our study evaluated the correlation between serum ApoB level and CKD to look for an alternative approach for CKD prevention and treatment in the general population. There were 146,533 participants in this cross-sectional study. 3,325 participants with more than 2 measurements were enrolled in the retrospective longitudinal study with at least a 3-year follow-up. ApoB was measured by the immunoturbidimetric method in 6 centers. Our study defined CKD as an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2. The Spearman rank correlation analysis and the Random Forest algorithm were applied to rank the importance of variables determining the levels of eGFR. We used the logistic regression model to explain the correlation between serum ApoB and CKD. We used the Cox model to detect the correlation between baseline serum ApoB and the subsequent occurrence of CKD. Based on a cross-sectional study, 66.5% of the participants were males, with a median age of 49 (interquartile range [IQR] 43-55). Compared to the non-CKD group, the CKD group has higher levels of lipid profile and fasting glucose as well as the proportion of hypertension and hyperuricemia. The Spearman rank correlation analysis and the Random Forest algorithm revealed that ApoB has the highest correlation with eGFR decline among lipid profiles. The logistic regression analysis revealed that ApoB had a positive correlation with the prevalence of CKD after fully controlling confounders (odds ratio [OR], 1.07; 95% confidence interval [CI]: 1.02-1.11). Moreover, baseline ApoB level was correlated with a new-onset CKD in the longitudinal cohort after full adjustment for confounding factors (hazard ratio [HR], 1.61; 95% CI: 1.02-2.54). The correlation between ApoB level and the new-onset CKD was consistently observed in all sensitivity analyses. Serum ApoB had the strongest correlation with CKD among all lipid variables. Moreover, high serum ApoB levels might precede the occurrence of CKD, suggesting that monitoring and reducing serum ApoB levels may provide an alternative method to prevent and treat CKD.

Apolipoprotein B Displays Superior Predictive Value Than Other Lipids for Long-Term Prognosis in Coronary Atherosclerosis Patients and Particular Subpopulations: A Retrospective Study

Accumulating evidence that apolipoprotein B (apoB) plays a critical role in predicting coronary heart disease (CHD) and future outcomes. The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines suggest that apoB can be an alternative to non-HDL-C or LDL-C in patients with high triglyceride levels, diabetes, obesity, metabolic syndrome, or very low LDL-C levels. This study explores whether apoB can also serve as predictive value for long-term major adverse cardiovascular events (MACEs) in normal people and specific coronary atherosclerosis patients. A total of 826 patients were followed up over 10 years, and the risk factors for MACEs were retrospectively analyzed in patients with CHD and particular subpopulations. All statistical analyses were performed in R software. Cox regressions were performed to assess independent risk factors of long-term MACEs in the atherosclerosis group and CHD subgroups. Kaplan-Meier survival curves were used to evaluate the survival rate for patients in different apoB quartiles, and receiver-operating characteristic curves were used to compare apoB and other lipids in predicting the presence of long-term MACE. apoB could be a "risk-enhancing factor" in patients with coronary atherosclerosis disease, whereas in the Normal population, LDL-C still acted as a major risk factor for predicting MACEs. apoB was a good risk predictor for long-term cardiovascular events in coronary atherosclerosis (AS) patients, including the AS group and CHD subpopulations (including CHD+triglyceride ≥2.3 mmol/L, CHD+diabetes mellitus, CHD+body mass index ≥25 kg/m2, or CHD+metabolic syndrome). In patients with CHD whose condition was complicated with diabetes, obesity, and metabolic syndrome, apoB performed better than other lipids in predicting the presence of myocardial infarction, hospitalization due to angina, and cardiac death. Despite achieving optimal LDL-C or non-HDL-C levels, patients with CHD are still at risk of worse survival if they are unable to reach a low apoB level (lower cut points such as 65 mg/dL). More attention should be paid to special populations with residual elevations of atherogenic particle numbers, and greater focus should be placed on lowering baseline apoB to achieve long-term benefits. However, given that this was an observational study, the association of baseline apoB level and long-term MACEs only was evaluated; it is unclear whether the emergence of MACEs would be influenced by the dynamic changes of apoB. Because this was a retrospective and observational analysis, bias in data analysis was unavoidable; thus, the results cannot be used to generalize implications to broader patient populations, and more large-scale clinical trials are required to verify these findings. (Clin Ther. 2022;44:1071-1092) © 2022 Elsevier HS Journals, Inc.

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background:Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain.Methods:The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models.Results:Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata <75, 75–<90, ≥90 mg/dL, respectively; Ptrend<0.0001) and after adjustment for low-density lipoprotein cholesterol (Ptrend=0.035). Higher baseline apoB stratum was associated with greater relative (Ptrend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54], and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, >35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa.Conclusions:In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

Paradoxical Association Between Baseline Apolipoprotein B and Prognosis in Coronary Artery Disease: A 36,460 Chinese Cohort Study.

BackgroundApolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) were identified targets for blood lipid management among coronary artery disease (CAD) patients. However, previous studies reported an inverse correlation between baseline LDL-C concentration and clinical outcomes. This study aims to explore the definite association between baseline ApoB and long-term prognosis.MethodsA total of 36,460 CAD patients admitted to Guangdong Provincial People's Hospital were enrolled and categorized into two groups: high ApoB (≥65 mg/dL) group and low ApoB (<65 mg/dL) group. The association between baseline ApoB and long-term all-cause mortality was evaluated by the Kaplan-Meier method, Cox regression analyses and restricted cubic splines.ResultsThe overall mortality was 12.49% (n = 4,554) over a median follow-up period of 5.01 years. Patients with low baseline ApoB levels were paradoxically more likely to get a worse prognosis. There was no obvious difference in risk of long-term all-cause mortality when only adjusted for age, gender, and comorbidity (aHR: 1.07, 95% CI: 0.99–1.16). When CONUT and total bilirubin were adjusted, the risk of long-term all-cause mortality would reduce in the low-ApoB (<65 mg/dL) group (aHR: 0.86, 95% CI: 0.78–0.96). In the fully covariable-adjusted model, patients in the ApoB <65 mg/d group had a 10.00% lower risk of long-term all-cause mortality comparing to patients with ApoB ≥65 mg/dL (aHR: 0.90; 95% CI:0.81–0.99).ConclusionThis study found a paradoxical association between baseline ApoB and long-term all-cause mortality. Malnutrition and bilirubin mainly mediate the ApoB paradox. Increased ApoB concentration remained linearly associated with an increased risk of long-term all-cause mortality.

Predictive value of a reduction in the level of high-density lipoprotein-cholesterol in patients with non-small-cell lung cancer undergoing radical resection and adjuvant chemotherapy: a retrospective observational study

BackgroundCancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown.MethodsNSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed.ResultsSerum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025).ConclusionsAdjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE.

BackgroundCardiovascular disease is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE). Traditional factors for cardiovascular risk (CVR) prediction are less robust in younger patients. More reliable CVR biomarkers are needed for JSLE patient stratification and to identify therapeutic approaches to reduce cardiovascular morbidity and mortality in JSLE.MethodsSerum metabolomic analysis (including >200 lipoprotein measures) was performed on a discovery (n=31, median age 19) and validation (n=31, median age 19) cohort of JSLE patients. Data was analysed using cluster, receiver operating characteristic analysis and logistic regression. RNA-sequencing assessed gene expression in matched patient samples.FindingsHierarchical clustering of lipoprotein measures identified and validated two unique JSLE groups. Group-1 had an atherogenic and Group-2 had an atheroprotective lipoprotien profile. Apolipoprotein(Apo)B:ApoA1 distinguished the two groups with high specificity (96.2%) and sensitivity (96.7%). JSLE patients with high ApoB:ApoA1 ratio had increased CD8+ T-cell frequencies and a CD8+ T-cell transcriptomic profile enriched in genes associated with atherogenic processes including interferon signaling. These metabolic and immune signatures overlapped statistically significantly with lipid biomarkers associated with sub-clinical atherosclerosis in adult SLE patients and with genes overexpressed in T-cells from human atherosclerotic plaque respectively. Finally, baseline ApoB:ApoA1 ratio correlated positively with SLE disease activity index (r=0.43, p=0.0009) and negatively with Lupus Low Disease Activity State (r=-0.43, p=0.0009) over 5-year follow-up.InterpretationMulti-omic analysis identified high ApoB:ApoA1 as a potential biomarker of increased cardiometabolic risk and worse clinical outcomes in JSLE. ApoB:ApoA1 could help identify patients that require increased disease monitoring, lipid modification or lifestyle changes.FundingLupus UK, The Rosetrees Trust, British Heart Foundation, UCL & Birkbeck MRC Doctoral Training Programme and Versus Arthritis.

Apolipoprotein B Levels Predict Future Development of Hypertension Independent of Visceral Adiposity and Insulin Sensitivity.

BackgroundHigh plasma apolipoprotein B (apoB) levels have been shown to be associated with hypertension, central obesity, and insulin resistance in cross-sectional research. However, it is unclear whether apoB levels predict future hypertension independent of body composition and insulin sensitivity. Therefore, we prospectively investigated whether plasma apoB concentrations independently predicted the risk of hypertension in a cohort of Japanese Americans.MethodsA total of 233 normotensive Japanese Americans (77 men, 156 women; mean age, 46.4±11.0 years) were followed over 10 years to monitor them for the development of hypertension. Fasting plasma concentrations of apoB, glucose, and insulin were measured at baseline. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The abdominal visceral and subcutaneous fat areas were measured at baseline using computed tomography. Logistic regression analysis was used to estimate the association between apoB concentrations and the odds of incident hypertension.ResultsThe 10-year cumulative incidence of hypertension was 21.5%. The baseline apoB level was found to be positively associated with the odds of incident hypertension over 10 years after adjustment for age, sex, body mass index, systolic blood pressure, abdominal visceral fat area, abdominal subcutaneous fat area, total plasma cholesterol concentration, diabetes status, and HOMA-IR at baseline (odds ratio and 95% confidence interval for a 1-standard deviation increase, 1.89 [1.06 to 3.37]; P=0.030).ConclusionHigher apoB concentrations predicted greater risks of future hypertension independent of abdominal visceral fat area and insulin sensitivity in Japanese Americans.

Serum apoB levels independently predict the development of non-alcoholic fatty liver disease: A 7-year prospective study.

Cross-sectional studies have shown that apolipoprotein B (apoB) is positively associated with the prevalence of non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the prospective relationship between the serum apoB levels and the development of NAFLD in a Chinese population. A cohort of 7077 initially NAFLD-free participants was enrolled in this prospectively study. The incidence of NAFLD was calculated among participants with different baseline serum apoB quintiles. Cox proportional hazards regression analyses were conducted to calculate the risks for incident NAFLD. During 41555 person-year follow-ups, 1139 incident NAFLD cases were identified. The baseline apoB levels were linear and positively correlated with NAFLD incidence. The incidence was 16.99, 22.63, 24.73, 37.51 and 42.77 per 1000 person-year follow-up for participants with baseline apoB levels in quintiles 1-5, respectively. Compared with participants with baseline apoB levels in quintile 1, the hazard ratios (95% confidence interval) for incident NAFLD were 1.353 (1.100-1.663), 1.482 (1.207-1.820), 2.232 (1.832-2.720) and 2.543 (2.082-3.106) for participants with baseline apoB levels in quintile 2-5, respectively. The hazard ratios were attenuated but remained statistically significant after adjusting for age, gender, body mass index and variables associated with metabolic syndrome. Elevated serum apoB levels independently predict an increased risk for incident NAFLD.

Can Apolipoproteins apoB and apoB/apoA1 Ratio Predict Future Cardiovascular Risk Post Acute Coronary Syndrome? A Retrospective Cohort Study

Background: Whether apolipoproteins B100 (ApoB) and ApoB/ApoA1 biomarkers can predict future cardiovascular events in patients with acute coronary syndrome (ACS) is unknown. We evaluated the association between these biomarkers and development of major adverse cardiovascular events within 12 months in patients with ACS. Methods: We used data from a prospective cohort study of 1149 patients (32% women) aged 55 years or less, hospitalized for ACS (January 2009-April 2013). Baseline ApoB and ApoA1 levels were measured within the first 4 days of hospitalization for ACS. Patients were followed for 12 months for the composite of death, recurrent ACS, need for recurrent revascularization, or re-hospitalization for cardiac causes. Results: After ACS, most patients had elevated ApoB levels (46% 0.8-1.1 g/L and 31% with >1.1 g/L). Patients with the lowest ApoB levels (<0.8 g/L) were more likely to be women, have a history of previous myocardial infarction, diabetes and to be prescribed statins compared with those with higher ApoB levels. There was no significant association with ApoB level and the risk of composite cardiovascular outcome after adjustment for age, sex, statin use, GRACE score, ACS severity and day of measurement (Hazard Ratio (HR) 0.79, 95% CI: 0.41-1.55). Increasing ApoB/ApoA1 ratio was also not associated with risk of developing composite cardiovascular events compared with lower ratios (HR 0.92 95% CI 0.45-1.87). Conclusion: ApoB level and ApoB/ApoA1 ratio do not predict future cardiovascular events post-ACS when measured in the first 4 days in patients aged less than 55 years.

Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study

BackgroundHigh levels of apolipoprotein B (apoB) have been shown to predict atherosclerotic cardiovascular disease (CVD) in adults even in the context of low levels of low-density lipoprotein cholesterol (LDL-C) or non–high-density lipoprotein cholesterol (non–HDL-C). ObjectivesThis study aimed to quantify the associations between apoB and the discordance between apoB and LDL-C or non–HDL-C in young adults and measured coronary artery calcium (CAC) in midlife. MethodsData were derived from a multicenter cohort study of young adults recruited at ages 18 to 30 years. All participants with complete baseline CVD risk factor data, including apoB and year 25 (Y25) CAC score, were entered into this study. Presence of CAC was defined as having a positive, nonzero Agatston score as determined by computed tomography. Baseline apoB values were divided into tertiles of 4 mutually exclusive concordant/discordant groups, based on median apoB and LDL-C or non–HDL-C. ResultsAnalysis included 2,794 participants (mean age: 25 ± 3.6 years; body mass index: 24.5 ± 5 kg/m2; and 44.4% male). Mean lipid values were as follows: total cholesterol: 177.3 ± 33.1 mg/dl; LDL-C: 109.9 ± 31.1 mg/dl; non–HDL-C: 124.0 ± 33.5 mg/dl; HDL-C: 53 ± 12.8 mg/dl; and apoB: 90.7 ± 24 mg/dl; median triglycerides were 61 mg/dl. Compared with the lowest apoB tertile, higher odds of developing Y25 CAC were seen in the middle (odds ratio [OR]: 1.53) and high (OR: 2.28) tertiles based on traditional risk factor–adjusted models. High apoB and low LDL-C or non–HDL-C discordance was also associated with Y25 CAC in adjusted models (OR: 1.55 and OR: 1.45, respectively). ConclusionsThese data suggest a dose–response association between apoB in young adults and the presence of midlife CAC independent of baseline traditional CVD risk factors.

CAN APOLIPOPROTEIN B LEVELS PREDICT CARDIOVASCULAR RISK POST ACUTE CORONARY SYNDROME?

Apolipoprotein B (ApoB) is a strong predictor of CV events in patients at high-risk for coronary artery disease. Whether ApoB is a viable prognostic marker in patients with acute coronary syndrome is unknown. We evaluated whether ApoB level predicted time to development of major adverse cardiovascular events in men and women with ACS aged 55 years or less at one year. We also compared its predictive utility in menopausal and perimenopausal women given hormone replacement therapy. We used data from a prospective cohort study of 1015 patients (30% women) aged 55 years or less, hospitalized for ACS and enrolled in the GENESIS PRAXY (GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary SYndrome) study (January 2009-September 2012). Baseline ApoB levels was measured during hospitalization for ACS. Patients were followed for one year for the composite of recurrent ACS, death, need for recurrent revascularization, or re-hospitalization for cardiac cause. 38% had ApoB levels <0.89g/L, 33% had levels 0.90-1.1g/L and 29% with levels >1.2g/L. Patients with the lowest ApoB levels were more likely to be women, have a history of unstable angina, previous MI and previous PCI and to be prescribed statins compared with higher ApoB levels. There was no statistically significant difference in the risk of composite CV outcome and increasing ApoB level (age/sex adjusted HR 0.49, 95%CI 0.22-1.08). In menopausal women, higher ApoB levels were associated with a reduction in the composite CV outcome (age/sex adjusted HR 0.24, 95%CI 0.06-0.92). ApoB does not predict CV outcomes post-MI in our population. Interestingly, higher ApoB levels showed trends towards better outcomes, especially in menopausal women. Future studies should focus on the role of ApoB as a predictor of CV outcomes in the non-acute setting.

Abstract MP72: Apolipoprotein B and Apolipoprotein B, LDL-C Discordance in Young Adults Are Associated With Coronary Artery Calcification at 25 Year Follow-Up: The Coronary Artery Disease in Young Adults (CARDIA) Study

Introduction: High ApoB has been shown to predict cardiovascular disease (CVD) in adults even in the context of low LDL-C. It is not known, however, if high ApoB and high ApoB, low LDL-C discordance in young adults are associated with coronary artery calcium (CAC) in mid-life. Methods: Data were derived from CARDIA, a multicenter study of the development and determinants of CVD risk factors in young adults recruited at ages 18 to 30. All participants with complete baseline CVD risk factor data, ApoB, and year-25 CAC score were included in this study. Baseline lipid fractions and ApoB were measured by standard assays. Year-25 CAC was assessed using two consecutive CT scans with presence of CAC defined as having a positive, non-zero Agatston score using the average of two scans. Baseline ApoB values were divided into tertiles. Four mutually exclusive concordant/discordant groups were created based on median ApoB and LDL-C. Logistic regression was performed for unadjusted and adjusted models. Results: 3496 participants were included [mean age=25±3.6, BMI=24.5±5Kg/m2, 44.4% male, and the following mean lipid values (mg/dL): total cholesterol=177.3±33.1, LDL-C=109.9±31.1, HDL-C=53±12.8, ApoB=90.7±24, median triglycerides=61(IQR 46-83)]. Compared with the lowest ApoB tertile, the middle [OR=1.55 (95% CI 1.22-1.95)] and high [OR=2.35 (95% CI 1.87-2.97)] tertiles exhibited increased odds of developing year-25 CAC in traditional risk factor-adjusted models. High ApoB, low LDL-C discordance was also associated with year-25 CAC in adjusted models [OR=1.57 (95% CI 1.12-2.20)]. Conclusions: These data suggest a dose-response association between ApoB in young adults and presence of mid-life CAC independent of baseline traditional CVD risk factors. High ApoB, low LDL-C discordance was also associated with year-25 CAC, suggesting that ApoB in young adults may help identify individuals with modest LDL-C levels who are at increased risk for subclinical atherosclerosis in mid-life.

Apolipoproteins are associated with new MRI lesions and deep grey matter atrophy in clinically isolated syndromes

ObjectivesThere is increasing evidence that serum lipoprotein cholesterol biomarkers are associated with disease progression in clinically isolated syndromes (CIS). Apolipoproteins (Apo) are recognition ligands that mediate the physiological interactions of...

Abstract P221: Genome-wide Association Study Evaluating Genetic Determinants of Rosuvastatin Effects on Lp-PLA 2 Mass and Activity

Aims: Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is a pro-inflammatory enzyme bound to LDL-C and other lipoproteins in circulation that is associated with increased cardiovascular risk. There is little data regarding genetic determinants of Lp-PLA 2 mass and activity, and no prior data are available addressing genetic determinants of statin-induced changes for this inflammatory biomarker. Methods and Results: We performed a genome-wide association study of Lp-PLA 2 mass and activity at baseline and after 12 months of rosuvastatin therapy (20 mg/day) among 6,851 participants of European ancestry from the JUPITER trial. Genome-wide associations (p&lt;5x10 -8 ) were identified in GCKR and CETP for baseline Lp-PLA 2 mass, and at MS4A4E and the APOC1 - APOE locus for baseline Lp-PLA 2 activity. A variant in PLA2G7 , the gene encoding the Lp-PLA 2 enzyme was associated with Lp-PLA2 activity (p=3.1x10 -7 ) at a sub-genome-wide significance (p&lt;5x10 -6 ); this association attained genome-wide significance after adjusting for either baseline apoB (p=2.9x10 -8 ) or HDL-C levels (p=2.5x10 -9 ). Two other sub-genome-wide associations with Lp-PLA 2 activity attained genome-wide significance after adjusting for baseline lipoproteins: at the PSRC1 - SORT1 locus (before adjustment, p=8.3x10 -7 ; adjusting for triglycerides, p=3.4x10 -8 ) and the TMEM49 locus (before adjustment p=3.8x10 -6 , adjusting for HDL-C p=1.4x10 -8 ). Among 2,673 statin-allocated participants, median reductions were approximately 30% for Lp-PLA 2 mass and activity (versus ~50% for LDL-C) after 12 months of statin therapy (all p-values &lt;0.001). Variants in ABCG2 and LPA were associated with statin-induced change in Lp-PLA 2 activity at genome-wide significance, and associations at sub-genome-wide significance (p&lt;5x10 -6 ) were observed for EDG7 , C14orf177 , NOX5 , AP3B2 and RNF213 . All associations, with the exception of AP3B2 , were substantially attenuated after adjustment for statin induced changes in LDL-C or apoB. Conclusion: Genome-wide associations at the MS4A4E and TMEM49 loci may reflect novel influences on circulating levels of Lp-PLA 2 activity. In addition, genome-wide determinants of rosuvastatin-induced change in Lp-PLA 2 activity were observed in ABCG2 and LPA , likely due to their impact on statin-induced LDL-C reduction.

Abstract: 1472 APOC-III CONTAINING LIPOPROTEINS AND RISK OF CORONARY HEART DISEASE

1472 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2 APOC-III CONTAINING LIPOPROTEINS AND RISK OF CORONARY HEART DISEASE C Mendivil, E Rimm, J Furtado, S Chiuve, F Sacks Nutrition, Harvard School of Public Health, Boston, MA Objectives Apolipoprotein CIII (apoCIII) influences lipoprotein metabolism and may promote atherosclerosis. Our aim was to compare VLDL and LDL with and without apoCIII as risk factors for coronary heart disease (CHD). Methods We followed CHD-free participants, 18,225 men from the Health Professionals Follow-up Study (HPFS) for 10 years, and 32,826 women from the Nurses Health Study (NHS) for 14 years; and selected 731 patients who had a fatal or non-fatal myocardial infarction (cases, 317 from NHS and 414 from HPFS). Using risk set sampling, cases were matched 1:1 to controls of the same age, date of blood collection and smoking status. We compared baseline apoB concentrations of VLDL with apoCIII (VLDL CIII+), VLDL without apoCIII (VLDL CIII-), LDL with apoCIII (LDL CIII+), and LDL without apoCIII (LDL CIII-) in cases and controls. Results After adjustment for matching factors, the relative risk (RR) of CHD in the highest versus lowest quintile was 2.02 (95% confidence interval [CI], 1.42 to 2.89) for VLDL CIII+, 2.36 (95% CI, 1.60 to 3.47) for VLDL CIII-, 2.66 (95% CI, 1.83 to 3.85) for LDL CIII+, and 1.70 (95% CI, 1.11 to 2.57) for LDL CIII(all P trend <0.001). After adjustment for LDL and HDL cholesterol and triglycerides, and mutual adjustment between LDL CIII+ and LDL CIII-; the association was significant for LDL CIII+ (RR=1.68, 95% CI, 1.05 to 2.68) but not for LDL CIII(RR=0.67, 95% CI, 0.38 to 1.18). The apoCIII concentrations of these lipoproteins were weaker predictors than their numbers (apoB concentrations). Conclusions ApoCIII containing LDL is the strongest risk factor for CHD among the apoB lipoproteins. Much of the risk attributed to LDL particles is due to LDL with apoCIII. Funding: NHLBI-NIH.

Evidence of QTLs on chromosomes 1q42 and 8q24 for LDL-cholesterol and apoB levels in the HERITAGE Family Study

Genome-wide multipoint linkage analyses were performed to identify chromosomal regions harboring genes influencing LDL-cholesterol, total apolipoprotein B (apoB), and LDL-apoB levels using 654 markers. They were assessed in a sedentary state (baseline) and after a 20 week endurance training program. Strong evidence for two quantitative trait loci (QTLs) for baseline levels was found. There is linkage evidence in black families on chromosomes 1q41-q44 [at marker D1S2860, 238 centimorgan (cM), with a maximum log of the odds (LOD) score of 3.7 for LDL-apoB] and in white families on chromosome 8q24 (at marker D8S1774, 142 cM, with LOD scores of 3.6, 3.3, and 2.5 for baseline LDL-cholesterol, LDL-apoB, and apoB, respectively). There were no strong signals for the lipoprotein training responses (as computed as the difference in posttraining minus baseline levels). In conclusion, QTLs for baseline apoB and LDL-cholesterol levels on chromosomes 1q41-q44 (in blacks) and 8q24 (in whites) were found. As there are no known strong candidate genes in these regions for lipids, follow-up studies to determine the source of those signals are needed.