Discordance among apoB, non-high-density lipoprotein cholesterol, and triglycerides: implications for cardiovascular prevention.

BACKGROUND AND AIMS: Despite growing evidence that apolipoprotein B (apoB) is the most accurate marker of atherosclerotic cardiovascular disease (ASCVD) risk, its adoption in clinical practice has been low. This investigation sought to determine whether low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), and triglycerides are sufficient for routine cardiovascular care. METHODS: A sample of 293 876 UK Biobank adults (age: 40-73 years, 42% men), free of cardiovascular disease, with a median follow-up for new-onset ASCVD of 11 years was included. Distribution of apoB at pre-specified levels of LDL-C, non-HDL-C, and triglycerides was examined graphically, and 10-year ASCVD event rates were compared for high vs. low apoB. Residuals of apoB were constructed after regressing apoB on LDL-C, non-HDL-C, and log-transformed triglycerides and used as predictors in a proportional hazards regression model for new-onset ASCVD adjusted for standard risk factors, including HDL-C. RESULTS: ApoB was highly correlated with LDL-C and non-HDL-C (Pearson's r = .96, P < .001 for both) but less so with log triglycerides (r = .42, P < .001). However, apoB ranges necessary to capture 95% of all observations at pre-specified levels of LDL-C, non-HDL-C, or triglycerides were wide, spanning 85.8-108.8 md/dL when LDL-C 130 mg/dL, 88.3-112.4 mg/dL when non-HDL-C 160 mg/dL, and 67.8-147.4 md/dL when triglycerides 115 mg/dL. At these levels (±10 mg/dL), 10-year ASCVD rates for apoB above mean + 1 SD vs. below mean - 1 SD were 7.3 vs. 4.0 for LDL-C, 6.4 vs. 4.6 for non-HDL-C, and 7.0 vs. 4.6 for triglycerides (all P < .001). With 19 982 new-onset ASCVD events on follow-up, in the adjusted model, residual apoB remained statistically significant after accounting for LDL-C and HDL-C (hazard ratio 1.06, 95% confidence interval 1.0-1.07), after accounting for non-HDL-C and HDL-C (hazard ratio 1.04, 95% confidence interval 1.03-1.06), and after accounting for triglycerides and HDL-C (hazard ratio 1.13, 95% confidence interval 1.12-1.15). None of the residuals of LDL-C, non-HDL-C, or of log triglycerides remained significant when apoB was included in the model. CONCLUSIONS: High variability of apoB at individual levels of LDL-C, non-HDL-C, and triglycerides coupled with meaningful differences in 10-year ASCVD rates and significant residual information contained in apoB for prediction of new-onset ASCVD events demonstrate that LDL-C, non-HDL-C, and triglycerides are not adequate proxies for apoB in clinical care.

Lipoprotein(a) and functional outcome of acute ischemic stroke when discordant with low-density lipoprotein cholesterol.

BACKGROUND: Several studies have indicated that residual cardiovascular risk might be associated with elevated lipoprotein(a) [Lp(a)] even in the setting of controlled low-density lipoprotein cholesterol (LDL-C). We aimed to prospectively examine the association between Lp(a) and unfavorable functional outcome among patients with acute ischemic stroke when Lp(a) and LDL-C were discordant. METHODS: Based on samples from the Infectious Factors, Inflammatory Markers and Prognosis of Acute Ischemic Stroke study, 973 patients with baseline plasma Lp(a) levels were included. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score of 3-6) at 6 months. Logistic regression models were used to estimate the risk for the primary outcome. Discordance analyses were performed, using difference in percentile units (>10 units), to detect the relative risk when Lp(a) and LDL-C were discordant. RESULTS: In total, 201 (20.7%) participants experienced major disability or death at 6 months. The multivariable-adjusted odds ratio (OR) for the highest quartile was 1.88 [95% confidence interval (CI): 1.16-3.04] compared with the lowest quartile. Each 1-SD higher log-Lp(a) was associated with a 23% increased risk (95% CI: 2%-47%) for the primary outcome. Compared with the concordant group, the high Lp(a)/low LDL-C discordant group was associated with increased risk for the primary outcome (adjusted OR: 1.59, 95% CI: 1.01-2.52). CONCLUSIONS: Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6 months. Discordantly high Lp(a)/low LDL-C was associated with an unfavorable functional outcome, supporting the predictive potential of plasma Lp(a) after ischemic stroke, especially when discordant with LDL-C. Key messages What is already known on this topic Previous studies have indicated that a positive association between increased lipoprotein(a) [Lp(a)] and cardiovascular disease risk remained even in patients who achieved controlled low-density lipoprotein cholesterol (LDL-C) levels. The findings of studies exploring the association between Lp(a) and unfavorable clinical outcomes of stroke were inconsistent, and whether Lp(a) can predict the risk of unfavorable functional outcome in stroke patients when Lp(a) and LDL-C levels are discordant remains unknown. What this study adds Elevated plasma Lp(a) levels were associated with increased risk of major disability and death at 6 months beyond LDL-C levels in acute ischemic stroke patients. How this study might affect research, practice, or policy The combination of LDL-C-lowering therapies and Lp(a)-lowering therapies may have better clinical efficacy for patients with ischemic stroke, and it is of great clinical interest to further explore this possibility in dedicated randomized trials.

Discordance between the triglyceride glucose index and HOMA-IR in incident albuminuria: a cohort study from China.

BACKGROUND: To date, there have no study comparing the associations between TyG index and HOMA-IR on the risk of incident albuminuria. Accordingly, the objective of the present study is to use discordance analysis to evaluate the diverse associations between TyG index and HOMA-IR on the risk of incident albuminuria. METHODS: A community-based prospective cohort study was performed with 2446 Chinese adults. We categorized participants into 4 concordance or discordance groups. Discordance was defined as a TyG index equal to or greater than the upper quartile and HOMA-IR less than the upper quartile, or vice versa. RESULTS: During a median follow-up period of 3.9 years, 203 of 2446 participants developed incident albuminuria (8.3%). In the multivariable logistic analyses, the high TyG index tertile group was associated with a 1.71-fold (95% confidence interval (CI) 1.07-2.72) higher risk of incident albuminuria, comparing with the low tertile group. Participants in TyG (+) & HOMA-IR (-) group had a greater risk of incident albuminuria compared with those in TyG (-) & HOMA-IR (-) group after multivariate adjustment. Subgroup analyses showed that low HOMA-IR and discordantly high TyG index was closely related to a highest risk of incident albuminuria in cardiovascular metabolic disorder subjects. CONCLUSIONS: Participants with a discordantly high TyG index had a significantly greater risk of incident albuminuria, especially in metabolic dysfunction subjects. The TyG index might be a better predictor of early stage of chronic kidney disease than HOMA-IR for subjects with metabolic abnormality.

CardIAP: calcium transients confocal image analysis tool.

One of the main topics of cardiovascular research is the study of calcium (Ca2+) handling, as even small changes in Ca2+ concentration can alter cell functionality (Bers, Annu Rev Physiol, 2014, 76, 107-127). Ionic calcium (Ca2+) plays the role of a second messenger in eukaryotic cells, associated with cellular functions such as cell cycle regulation, transport, motility, gene expression, and regulation. The use of fluorometric techniques in isolated cells loaded with Ca2+-sensitive fluorescent probes allows quantitative measurement of dynamic events occurring in living, functioning cells. The Cardiomyocytes Images Analyzer Python (CardIAP) application addresses the need to analyze and retrieve information from confocal microscopy images systematically, accurately, and rapidly. Here we present CardIAP, an open-source tool developed entirely in Python, freely available and useable in an interactive web application. In addition, CardIAP can be used as a standalone Python library and freely installed via PIP, making it easy to integrate into biomedical imaging pipelines. The images that can be generated in the study of the heart have the particularity of requiring both spatial and temporal analysis. CardIAP aims to open the field of cardiomyocytes and intact hearts image processing. The improvement in the extraction of information from the images will allow optimizing the usage of resources and animals. With CardIAP, users can run the analysis to both, the complete image, and portions of it in an easy way, and replicate it on a series of images. This analysis provides users with information on the spatial and temporal changes in calcium releases and characterizes them. The web application also allows users to extract calcium dynamics data in downloadable tables, simplifying the calculation of alternation and discordance indices and their classification. CardIAP aims to provide a tool that could assist biomedical researchers in studying the underlying mechanisms of anomalous calcium release phenomena.

Discordance of apolipoprotein B with low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol and coronary atherosclerosis.

AIMS: High level of apolipoprotein B (Apo B) is associated with incident subclinical atherosclerosis. The present study evaluated the associations between discordant Apo B with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and coronary atherosclerotic burden. METHODS AND RESULTS: This study enrolled 3043 participants aged 50-75 years from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study that was conducted in the community in Lishui City, China. Discordant Apo B with LDL-C and non-HDL-C were defined by residuals and medians. Coronary atherosclerotic burden was evaluated by segment involvement score (SIS) and segment stenosis score (SSS) which were determined by computed tomography angiography. We performed discordance analyses examining associations of discordant Apo B with LDL-C or non-HDL-C with the coronary atherosclerotic burden. The mean age of participants was 61.2 ± 6.7 years, 53.6% were females. Participants with discordant high Apo B relative to non-HDL-C were at higher odds of plaques [odds ratio (OR), 1.30; 95% confidence interval (CI), 1.08-1.57], SIS [common odds ratio (cOR), 1.35; 95% CI, 1.14-1.60], and SSS (cOR, 1.40; 95% CI, 1.18-1.67) compared with concordant group. However, discordantly low Apo B with non-HDL-C was associated with decreased odds of the coronary atherosclerotic plaques and its burden. Similar results were shown for discordant analyses for Apo B with LDL-C. CONCLUSION: Discordantly high Apo B with LDL-C and non-HDL-C were associated with an increased odds of the coronary atherosclerotic plaques and its burden. These findings highlighted the importance of Apo B for primary prevention of coronary atherosclerosis.

Apolipoprotein B vs non-high-density lipoprotein cholesterol: Association with endothelial hemostatic markers and carotid intima-media thickness.

BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for lipid-lowering therapy, which correlate more strongly with cardiovascular events than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross-sectional study was to evaluate the differences in plasma levels of plasminogen activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic marker for atherosclerotic vascular disease among dyslipidemic individuals with apoB levels higher, estimated or lower based on regression equation of apoB vs non-HDL-C. METHODS: A total of 594 dyslipidemic subjects without atherosclerotic manifestation were divided into 3 groups (according to tertiles of apoB levels above, within, and below the line of identity): H-apoB (n = 200), E-apoB (n = 194), and L-apoB (n = 200). PAI-1, vWF, C-IMT and lipids, anthropometric parameters, markers of insulin resistance, and inflammation were measured. Differences in variables between groups were analyzed using analysis of variance. RESULTS: There was a strong association between apoB and non-HDL-C. The correlations of apoB and of non-HDL-C with markers of endothelial damage and C-IMT were very similar. Despite these facts, individuals with higher apoB levels had significantly higher levels of PAI-1 compared with individuals with estimated (P < .05) or lower apoB (P < .001). There were no significant differences in vWF, C-IMT, markers of insulin resistance, obesity, and inflammation. CONCLUSION: Individuals with apoB higher than predicted by non-HDL-C had significantly higher levels of PAI-1, which may contribute to the increased risk of future atherothrombotic events.