Apolipoproteins are important structural components of plasma lipoproteins that influence vascular biology and atherosclerotic disease pathophysiology by regulating lipoprotein metabolism. Clinically ...important apolipoproteins related to lipid metabolism and atherogenesis include apolipoprotein B-100, apolipoprotein B-48, apolipoprotein A-I, apolipoprotein C-II, apolipoprotein C-III, apolipoprotein E and apolipoprotein(a). Apolipoprotein B-100 is the major structural component of VLDL, IDL, LDL and lipoprotein(a). Apolipoprotein B-48 is a truncated isoform of apolipoprotein B-100 that forms the backbone of chylomicrons. Apolipoprotein A-I provides the scaffolding for lipidation of HDL and has an important role in reverse cholesterol transport. Apolipoproteins C-II, apolipoprotein C-III and apolipoprotein E are involved in triglyceride-rich lipoprotein metabolism. Apolipoprotein(a) covalently binds to apolipoprotein B-100 to form lipoprotein(a). In this Review, we discuss the mechanisms by which these apolipoproteins regulate lipoprotein metabolism and thereby influence vascular biology and atherosclerotic disease. Advances in the understanding of apolipoprotein biology and their translation into therapeutic agents to reduce the risk of cardiovascular disease are also highlighted.
Elevated lipoprotein(a) (Lpa) and family history (FHx) of coronary heart disease (CHD) are individually associated with cardiovascular risk, and Lp(a) is commonly measured in those with FHx.
The aim ...of this study was to determine independent and joint associations of Lp(a) and FHx with atherosclerotic cardiovascular disease (ASCVD) and CHD among asymptomatic subjects.
Plasma Lp(a) was measured and FHx was ascertained in 2 cohorts. Elevated Lp(a) was defined as the highest race-specific quintile. Independent and joint associations of Lp(a) and FHx with cardiovascular risk were determined using Cox regression models adjusted for cardiovascular risk factors.
Among 12,149 ARIC (Atherosclerosis Risk In Communities) participants (54 years, 56% women, 23% black, 44% with FHx), 3,114 ASCVD events were observed during 21 years of follow-up. FHx and elevated Lp(a) were independently associated with ASCVD (hazard ratio HR: 1.17; 95% confidence interval CI: 1.09 to 1.26, and HR: 1.25; 95% CI: 1.12 to 1.40, respectively), and no Lp(a)-by-FHx interaction was noted (p = 0.75). Compared with subjects without FHx and nonelevated Lp(a), those with either elevated Lp(a) or FHx were at a higher ASCVD risk, while those with both had the highest risk (HR: 1.43; 95% CI: 1.27 to 1.62). Similar findings were observed for CHD risk in ARIC, in analyses stratified by premature FHx, and in an independent cohort, the DHS (Dallas Heart Study). Presence of both elevated Lp(a) and FHx resulted in greater improvement in ASCVD and CHD risk reclassification and discrimination indexes than either marker alone.
Elevated plasma Lp(a) and FHx have independent and additive joint associations with cardiovascular risk and may be useful concurrently for guiding primary prevention therapy decisions.
Socioeconomic status is an overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend greater CVD risk. Therefore, we assessed the ...association of family income with cardiovascular risk factor and disease burden in American adults. This retrospective analysis included data from participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The association of PIR with the presence of cardiovascular risk factors and CVD as well as cardiac mortality and all-cause mortality was examined. We included 35,932 unweighted participants corresponding to 207,073,472 weighted, nationally representative participants. Participants with lower PIR were often female and more likely to belong to race/ethnic minorities (non-Hispanic Black, Mexican American, other Hispanic). In addition, they were less likely to be married/living with a partner, to attain college graduation or higher, or to have health insurance. In adjusted analyses, the prevalence odds of diabetes mellitus, hypertension, coronary artery disease (CAD), congestive heart failure (CHF), and stroke largely decreased in a step-wise manner from highest (≥ 5) to lowest PIR (< 1). In adjusted analysis, we also noted a mostly dose-dependent association of PIR with the risk of all-cause and cardiac mortality during a mean 5.7 and 5.8 years of follow up, respectively. Our study demonstrates a largely dose-dependent association of PIR with hypertension, diabetes mellitus, CHF, CAD and stroke prevalence as well as incident all-cause mortality and cardiac mortality in a nationally representative sample of American adults. Public policy efforts should be directed to alleviate these disparities to help improve cardiovascular outcomes in vulnerable groups with low family income.
Purpose
While low density lipoprotein cholesterol (LDL-C) remains a key contributor of atherosclerotic cardiovascular disease (ASCVD), additional risk factors identified through epidemiological and ...genetic studies have ushered in a fertile era of drug discovery in lipid-lowering therapy. Unlike contemporary small molecule medications, many of the novel agents are biologics utilizing monoclonal antibody (mAb) or RNA interference (RNAi) technologies. This report aims to review the evidence to date, focusing on completed and ongoing clinical trials and how these new agents will impact clinical practice.
Methods
We review data from pertinent studies on lipid-lowering biologics in clinical use or have translated to human studies and are undergoing clinical trials.
Results
Several targets affecting lipid metabolism have been identified to be causally associated with ASCVD including proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein 3 (ANGPTL3), apolipoprotein C3 (APOC3), and lipoprotein (a) (Lpa). Biotechnological modalities that have been developed for these targets include mAb, small interfering RNA (siRNA), and anti-sense oligonucleotide (ASO) agents. Agents such as alirocumab and evolocumab have shown efficacy in risk reduction of ASCVD in cardiovascular outcome trials and have been incorporated into evidence-based practice guidelines. Other agents included in this review are in various stages of clinical trials and have shown significant efficacy in the reduction of lipid parameters.
Conclusion
The development of new biologics targeting lipid risk factors will provide clinicians additional tools to reduce the risk for ASCVD. Important factors to consider will be cost-effectiveness and improving methods to personalize treatments to risk factors.
Due to the COVID-19 pandemic’s rapid expansion, the creation of vaccines is crucial for lowering disease transmission. Therefore, to determine the safety and efficacy of the vaccine against ...symptomatic illness and to evaluate breakthrough infections, those who received single or both the doses of vaccine against COVID-19 infection. A retrospective observational study was carried out on vaccine efficacy and the incidence of the breakthrough infections among the heath care workers, support staff and administrative staff. Out of 599 fully vaccinated health care workers, those who tested COVID-19 positive post-vaccination only 1.16% developed a severe illness that necessitates hospitalization. This study reflects a significant vaccine efficacy of 81.3% after a complete dose of vaccination and protection of 76.9% after one standard dose against symptomatic disease. The frequency of COVID-19 vaccine breakthrough is very low, which means that COVID-19 vaccines are highly effective at preventing COVID-19, particularly when it comes to severity.
Author Affiliation: (1) Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA (2) Emory Clinical Cardiovascular Research Institute, Atlanta, GA, USA ...(d) aquyyum@emory.edu Article History: Registration Date: 01/02/2021 Received Date: 07/07/2020 Accepted Date: 01/01/2021 Online Date: 01/19/2021 Byline:
Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic ...factors, including LPA kringle IV‐2 domain size, single‐nucleotide polymorphisms, and interleukin‐1 genotypes. Apolipoprotein(a) is encoded by the LPA gene and contains 10 subtypes with a variable number of copies of kringle ‐2, resulting in >40 different apolipoprotein(a) isoform sizes. Genetic loci beyond LPA , such as APOE and APOH , have been shown to impact lipoprotein(a) levels. Lipoprotein(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3‐fold difference in median lipoprotein(a) concentrations between racial and ethnic populations. Nongenetic factors, including menopause, diet, and renal function, may also impact lipoprotein(a) concentration. Lipoprotein(a) levels are also influenced by inflammation since the LPA promoter contains an interleukin‐6 response element; interleukin‐6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels. Screening can identify elevated lipoprotein(a) levels and facilitate intensive risk factor management. Several investigational, RNA‐targeted agents have shown promising lipoprotein(a)‐lowering effects in clinical studies, and large‐scale lipoprotein(a) testing will be fundamental to identifying eligible patients should these agents become available. Lipoprotein(a) testing requires routine, nonfasting blood draws, making it convenient for patients. Herein, we discuss the genetic determinants of lipoprotein(a) levels, explore the pathophysiological mechanisms underlying the association between lipoprotein(a) and cardiovascular disease, and provide practical guidance for lipoprotein(a) testing.
The present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian ...centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25-94.98), 96.17% (95.2-97.15) and 91.83% (90.36-93.31), respectively, and the corresponding DFS were 88.1% (86.96-89.31), 92.0% (90.64-93.39) and 83.93% (82.03-85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12-97.1), 92.74% (90.73-94.8) and 90.62% (88.17-93.15), respectively, and the corresponding DFS were 91.59% (90.19-93.02), 85.46% (82.79-88.22) and 81.29% (78.11-84.61), respectively. This is the largest dataset of early breast cancer patients from India with survival outcome analysis and can therefore serve as a benchmark for future studies.
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