Lipid Cardiovascular Disease Research Articles

A Systematic Review of Lipid-Focused Cardiovascular Disease Research: Trends and Opportunities.

Lipids are important modifiers of protein function, particularly as parts of lipoproteins, which transport lipophilic substances and mediate cellular uptake of circulating lipids. As such, lipids are of particular interest as blood biological markers for cardiovascular disease (CVD) as well as for conditions linked to CVD such as atherosclerosis, diabetes mellitus, obesity and dietary states. Notably, lipid research is particularly well developed in the context of CVD because of the relevance and multiple causes and risk factors of CVD. The advent of methods for high-throughput screening of biological molecules has recently resulted in the generation of lipidomic profiles that allow monitoring of lipid compositions in biological samples in an untargeted manner. These and other earlier advances in biomedical research have shaped the knowledge we have about lipids in CVD. To evaluate the knowledge acquired on the multiple biological functions of lipids in CVD and the trends in their research, we collected a dataset of references from the PubMed database of biomedical literature focused on plasma lipids and CVD in human and mouse. Using annotations from these records, we were able to categorize significant associations between lipids and particular types of research approaches, distinguish non-biological lipids used as markers, identify differential research between human and mouse models, and detect the increasingly mechanistic nature of the results in this field. Using known associations between lipids and proteins that metabolize or transport them, we constructed a comprehensive lipid-protein network, which we used to highlight proteins strongly connected to lipids found in the CVD-lipid literature. Our approach points to a series of proteins for which lipid-focused research would bring insights into CVD, including Prostaglandin G/H synthase 2 (PTGS2, a.k.a. COX2) and Acylglycerol kinase (AGK). In this review, we summarize our findings, putting them in a historical perspective of the evolution of lipid research in CVD.

Heritability and family-based GWAS analyses of the N-acyl ethanolamine and ceramide plasma lipidome.

Signalling lipids of the N-acyl ethanolamine (NAE) and ceramide (CER) classes have emerged as potential biomarkers of cardiovascular disease (CVD). We sought to establish the heritability of plasma NAEs (including the endocannabinoid anandamide) and CERs, to identify common DNA variants influencing the circulating concentrations of the heritable lipids, and assess causality of these lipids in CVD using 2-sample Mendelian randomization (2SMR). Nine NAEs and 16 CERs were analyzed in plasma samples from 999 members of 196 British Caucasian families, using targeted ultra-performance liquid chromatography with tandem mass spectrometry. All lipids were significantly heritable (h2 = 36–62%). A missense variant (rs324420) in the gene encoding the enzyme fatty acid amide hydrolase (FAAH), which degrades NAEs, associated at genome-wide association study (GWAS) significance (P < 5 × 10−8) with four NAEs (DHEA, PEA, LEA and VEA). For CERs, rs680379 in the SPTLC3 gene, which encodes a subunit of the rate-limiting enzyme in CER biosynthesis, associated with a range of species (e.g. CER[N(24)S(19)]; P = 4.82 × 10−27). We observed three novel associations between SNPs at the CD83, SGPP1 and DEGS1 loci, and plasma CER traits (P < 5 × 10−8). 2SMR in the CARDIoGRAMplusC4D cohorts (60 801 cases; 123 504 controls) and in the DIAGRAM cohort (26 488 cases; 83 964 controls), using the genetic instruments from our family-based GWAS, did not reveal association between genetically determined differences in CER levels and CVD or diabetes. Two of the novel GWAS loci, SGPP1 and DEGS1, suggested a casual association between CERs and a range of haematological phenotypes, through 2SMR in the UK Biobank, INTERVAL and UKBiLEVE cohorts (n = 110 000–350 000).

Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting.

With cardiovascular disease being the leading cause of morbidity and mortality worldwide, effective and cost-efficient therapies to reduce cardiovascular risk are highly needed. Lipids and lipoprotein particles crucially contribute to atherosclerosis as underlying pathology of cardiovascular disease and influence inflammatory processes as well as function of leukocytes, vascular and cardiac cells, thereby impacting on vessels and heart. Statins form the first-line therapy with the aim to block cholesterol synthesis, but additional lipid-lowering drugs are sometimes needed to achieve low-density lipoprotein (LDL) cholesterol target values. Furthermore, beyond LDL cholesterol, also other lipid mediators contribute to cardiovascular risk. This review comprehensively discusses low- and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides as well as fatty acids and derivatives in the context of cardiovascular disease, providing mechanistic insights into their role in pathological processes impacting on cardiovascular disease. Also, an overview of applied as well as emerging therapeutic strategies to reduce lipid-induced cardiovascular burden is provided.

Reference Intervals for Non-Fasting CVD Lipids and Inflammation Markers in Pregnant Indigenous Australian Women.

Indigenous Australians experience high rates of cardiovascular disease (CVD). The origins of CVD may commence during pregnancy, yet few serum reference values for CVD biomarkers exist specific to the pregnancy period. The Gomeroi gaaynggal research project is a program that undertakes research and provides some health services to pregnant Indigenous women. Three hundred and ninety-nine non-fasting samples provided by the study participants (206 pregnancies and 175 women) have been used to construct reference intervals for CVD biomarkers during this critical time. A pragmatic design was used, in that women were not excluded for the presence of chronic or acute health states. Percentile bands for non-linear relationships were constructed according to the methods of Wright and Royston (2008), using the xriml package in StataIC 13.1. Serum cholesterol, triglycerides, cystatin-C and alkaline phosphatase increased as gestational age progressed, with little change seen in high-sensitivity C-Reactive Protein and γ glutamyl transferase. Values provided in the reference intervals are consistent with findings from other research projects. These reference intervals will form a basis with which future CVD biomarkers for pregnant Indigenous Australian women can be compared.

Abstract 282: A Drosophila Model of Cardiac Lipotoxicity

Obesity is associated with cardiovascular disease in humans and a number of model organisms, including the fruit fly Drosophila melanogaster . We use a fly model of high-sugar-diet-induced metabolic disease that includes hyperglycemia, insulin resistance, obesity, cardiovascular disease, and reduced longevity. High-sugar-fed flies accumulate lipids in a variety of organs, including the heart. We are using tissue-specific metabolomics and loss-of-function genetics to probe the roles of individual organs and lipids in cardiovascular disease. Our goal is to focus on conserved pathways to better understand how overnutrition with high-calorie diets leads to adverse outcomes in patients with complications of type 2 diabetes.

Improving the odds: ezetimibe and cardiovascular disease.

The beauty of science is that well-conducted experiments provide answers to questions which were posed in times of greater ignorance. Cardiovascular disease (CVD) is the leading cause of death worldwide and will be for some time. Cholesterol is a critical player which drives the underlying pathophysiological process of atherosclerosis. Statins are the first line treatment for lipids in CVD given their ability to low-density lipoprotein cholesterol (LDL-C) by up to 50%, and their proven benefits in both primary and secondary intervention . Despite the unprecedented efficacy of statins, additional treatments are sought to potentially reduce the residual risk that remains despite statin treatment such as that associated with reduced high-density lipoprotein cholesterol levels (HDL-C) or triglycerides . In the last 5 years, several trials have reported on their potential additional benefit beyond statin therapy. These include omega-3 fatty acids in patients with prediabetes or diabetes , fibrates in diabetes , nicotinic acid/niacin in cardiovascular disease and cholesterol ester transfer protein inhibitors in cardiovascular disease . Despite their promise, none of these treatments were able to demonstrate benefit beyond baseline statin therapy when compared with placebo . The idea that benefit beyond statin treatment may be an unachievable goal has dogged the medical community working on CVD prevention. The phrase, 'Statins for atherosclerosis - as good as it gets?' was coined in 2005 and has rung true up until now .

Lipoproteins and diabetes.

Ever since the French–German pathologist Jean Lobstein coined the term arteriosclerosis in 1833,1 the disease has been intensively investigated. In 1793, Edward Jenner, later a celebrity for his contribution to small pox vaccination, performed an autopsy on his colleague John Hutner who had died suddenly during a heated discussion at a board meeting at St Georges Hospital in London. In his notes he wrote: ‘I found no material disease of the heart, except that the coronary arteries were thickened’.2 Rudolf Virchow was the first to recognize the inflammatory nature of atherosclerosis and the role of lipids therein,3 a concept that is still stands true today.4 It was a Russian military physician, however, who—behind the Iron Curtain in 1913—proved the concept by feeding rabbits with a high-fat diet. With his experiment, Nikolai N. Anichkov showed that lipid-rich plaques had developed under these circumstances in the aorta of the animals.5 Once the Framingham study confirmed the importance of high cholesterol for the development of myocardial infarction, stroke, and death in US and European populations,6 cholesterol became a therapeutic target. Thanks to the discovery of Akiro Endo,7 statins, together with antihypertensive drugs and aspirin, became a cornerstone in cardiovascular prevention8 and contributed to the rise of cardiovascular medicine.9 Today, LDL cholesterol (LDL-C) and statins are used extensively in clinical practice and are part of several guidelines of the European Society of Cardiology in individuals at risk10,11 and patients with established coronary artery disease.12 The current issue of the European Heart Journal focuses on lipoproteins and diabetes. In spite of all the progress made, several aspects of lipids in cardiovascular disease remain unresolved, in …

Treating lipids in cardiovascular disease: new directions

Aims To review the importance of lipid parameters beside low-density lipoprotein (LDL) levels as risk factors for cardiovascular disease, and their potential as therapeutic targets for lipid-lowering agents. Methods and Results Large numbers of studies have shown that, as well as high low-density lipoprotein (LDL) levels, low high-density lipoprotein (HDL) levels and a high LDL/HDL ratio are important cardiovascular disease risk factors. The new generation of statins, such as cerivastatin, demonstrates greater potency in getting more patients to their LDL-C targets, as recommended by the U.S. NCEP guidelines. Statins and also fibrates can increase HDL levels. In the VA-HIT study, for example, a 6% increase in HDL level using gemfibrozil was associated with a 22% reduction in the relative risk of coronary events compared with placebo. Statin treatment, by decreasing LDL and increasing HDL levels, produces strong reductions in the LDL/HDL ratio. In a cerivastatin study, the percentage of patients with LDL/HDL ratio <3 (low risk of coronary heart disease) increased from 32% (baseline) to 90% after 8 weeks of therapy. The density of LDL particles also affects cardiovascular disease risk. Studies have shown that small dense LDL particles have atherogenic properties, and that lipid-lowering therapy can alter the LDL density profile. The TRIGMA trial is investigating the effect of cerivastatin on LDL particle size and triglyceride levels in patients with type 2 diabetes. Conclusions Other lipid parameters, besides LDL levels, can provide new targets for lipid intervention therapy.

Lipid clinics/cardiovascular risk reduction clinics: current state and future consideration.

There are three primary objectives: 1 Specialty care for both primary and secondary prevention of coronary artery disease (CAD) 2 Education for public and health professionals 3 Research centered on the understanding of the role of lipids in cardiovascular disease.

Lipids in cardiovascular disease

Lipids in cardiovascular disease

Magnesium and lipids in cardiovascular disease.

(1986). Magnesium and lipids in cardiovascular disease. Journal of the American College of Nutrition: Vol. 5, No. 6, pp. 507-19.