A long-standing association exists between elevated triglyceride levels and cardiovascular disease* (CVD).1,2 However, the extent to which triglycerides directly promote CVD or represent a biomarker of risk has been debated for 3 decades.3 To this end, 2 National Institutes of Health consensus conferences evaluated the evidentiary role of triglycerides in cardiovascular risk assessment and provided therapeutic recommendations for hypertriglyceridemic states.4,5 Since 1993, additional insights have been made vis-a-vis the atherogenicity of triglyceride-rich lipoproteins (TRLs; ie, chylomicrons and very low-density lipoproteins), genetic and metabolic regulators of triglyceride metabolism, and classification and treatment of hypertriglyceridemia. It is especially disconcerting that in the United States, mean triglyceride levels have risen since 1976, in concert with the growing epidemic of obesity, insulin resistance (IR), and type 2 diabetes mellitus (T2DM).6,7 In contrast, mean low-density lipoprotein cholesterol (LDL-C) levels have receded.7 Therefore, the purpose of this scientific statement is to update clinicians on the increasingly crucial role of triglycerides in the evaluation and management of CVD risk and highlight approaches aimed at minimizing the adverse public health–related consequences associated with hypertriglyceridemic states. This statement will complement recent American Heart Association scientific statements on childhood and adolescent obesity8 and dietary sugar intake9 by emphasizing effective lifestyle strategies designed to lower triglyceride levels and improve overall cardiometabolic health. It is not intended to serve as a specific guideline but will be of value to the Adult Treatment Panel IV (ATP IV) of the National Cholesterol Education Program, from which evidence-based guidelines will ensue. Topics to be addressed include epidemiology and CVD risk, ethnic and racial differences, metabolic determinants, genetic and family determinants, risk factor correlates, and effects related to nutrition, physical activity, and lipid medications.

In the United States, the National Health and …

https://www.ahajournals.org/doi/pdf/10.1161/CIR.0b013e3182160726

Triglycerides and Cardiovascular Disease A Scientific Statement From the American Heart Association

Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year. Evidence for genetic influence on smoking behaviour and nicotine dependence (ND) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health. Smoking is the major risk factor for lung cancer (LC) and is one of the main risk factors for peripheral arterial disease (PAD). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking-related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genome-wide association study that used low-quantity smokers as controls, and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene-environment interaction, highlighting the role of nicotine addiction in the pathology of other serious diseases.

A variant associated with nicotine dependence, lung cancer and peripheral arterial disease.

/pdf/triglycerides-and-cardiovascular-disease-a-scientific-25jmfgszcb.pdf

Triglycerides and Cardiovascular Disease : A Scientific Statement From the

Atherosclerotic vascular disease arises as a consequence of the deposition and retention of serum lipoproteins in the artery wall. Macrophages in lesions have been shown to express ≥6 structurally different scavenger receptors for uptake of modified forms of low-density lipoproteins (LDLs) that promote the cellular accumulation of cholesterol. Because cholesterol-laden macrophage foam cells are the primary component of the fatty streak, the earliest atherosclerotic lesion, lipid uptake by these pathways has long been considered a requisite and initiating event in the pathogenesis of atherosclerosis. Although the removal of proinflammatory modified LDLs from the artery wall via scavenger receptors would seem beneficial, the pathways distal to scavenger receptor uptake that metabolize the modified lipoproteins appear to become overwhelmed, leading to the accumulation of cholesterol-laden macrophages and establishment of a chronic inflammatory setting. These observations have led to the current dogma concerning scavenger receptors, which is that they are proatherogenic molecules. However, recent studies suggest that the effects of scavenger receptors on atherogenesis may be more complex. In addition to modified lipoprotein uptake, these proteins are now known to regulate apoptotic cell clearance, initiate signal transduction, and serve as pattern recognition receptors for pathogens, activities that may contribute both to proinflammatory and anti-inflammatory forces regulating atherogenesis. In this review, we focus on recent advances in our knowledge of scavenger receptor regulation and signal transduction, their roles in sterile inflammation and infection, and the potential impact of these pathways in regulating the balance of lipid accumulation and inflammation in the artery wall.

Scavenger Receptors in Atherosclerosis: Beyond Lipid Uptake

In the year 2003 there was a 17% increase in the number of publications citing work performed using optical biosensor technology compared with the previous year. We collated the 962 total papers for 2003, identified the geographical regions where the work was performed, highlighted the instrument types on which it was carried out, and segregated the papers by biological system. In this overview, we spotlight 13 papers that should be on everyone's 'must read' list for 2003 and provide examples of how to identify and interpret high-quality biosensor data. Although we still find that the literature is replete with poorly performed experiments, over-interpreted results and a general lack of understanding of data analysis, we are optimistic that these shortcomings will be addressed as biosensor technology continues to mature.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jmr.753

Survey of the year 2003 commercial optical biosensor literature


 
 
 Type of funding sources: Other. Main funding source(s): Austrian National Bank
 Unlimited scientific grant from the Boston Scientific Investigator Sponsored Research (ISR) Committee
 
 
 
 Current heart failure (HF) guidelines recommend optimal medical therapy (OMT) in patients with pacing-induced cardiomyopathy (PICM) prior upgrading to cardiac resynchronisation therapy (CRT). It is unknown, whether previous prescription of heart failure medication reduces the effect of CRT upgrading.
 
 
 
 To evaluate the effect of HF medication on CRT response in patients suffering from PICM receiving an upgrade to CRT.
 
 
 
 The UPGRADE trial was a prospective investigator driven trial evaluating the effect of CRT upgrading in patients with PICM. Key inclusion criteria were symptomatic HF with left ventricular ejection fraction (LVEF) below 40% despite OMT and right ventricular pacing (RVP) above 40%. Device programming had to be adjusted to minimize RVP prior to enrolment. Echocardiographic examinations were performed prior to device implantation and 3-5 months after activation of CRT and were analyzed in blinded fashion. CRT response was defined by a reduction of > 15% in left ventricular end systolic volume (LVESV). Heart failure medication was assessed at implantation of the device.
 
 
 
 Overall, 54 patients were enrolled in the UPGRADE trial between 2014 and 2018. Beta-blockers (BB) were prescribed in 43 (79.6%), mineralcorticoid receptor antagonists (MRA) in 29 (53.7%) and either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blockers (ARB) in 45 (83.3%) of the patients. Therapy with CRT has led to significant improvement in LVEF (mean delta: 12.8 ± 7.8%) and LVESV (delta: 30.7 ± 33.2ml), whereas CRT response was achieved in 30 (55.6%) patients. There was no statistically significant difference in patients with BB intake regarding increase of LVEF (12.4 ± 7.5% vs. 14.6 ± 9.4%, p=0.431), decrease of LVESV (42.8 ± 32.8ml vs. 27.8 ± 33.0ml, p=0.201) or CRT response (22 (53.7%) vs. 8 (80%), p=0.167). Similar results were found regarding ACE inhibitor/ARB [LVEF: 13.1 ± 6.8% vs. 11.5 ± 11.8%, p=0.705; LVESV: 32.6 ± 32.6ml vs. 21.7 ± 36.3ml, p=0.373; CRT response: 26 (61.9%) vs. 4 (44.4%), p=0.460] and MRA intake [LVEF: 13.7 ± 7.3% vs. 11.8 ± 8.4%, p=0.382; LVESV: 34.3 ± 36.8ml vs. 26.7 ± 28.8ml, p=0.423; CRT response: 15 (55.6%) vs. 15 (62.5%), p=0.777].
 
 
 
 Previous prescription of heart failure medication did not reduce the effect of CRT upgrading in patients suffering from PICM. It remains to be proven, whether similar results may be observed for newer HF agents like sodium-glucose co-transporter 2 inhibitors or angiotensin receptor-neprilysin inhibitors as both were not available in clinical routine at the time of study conduct.


Heart failure medication and its effect on response to cardiac resynchronisation therapy in patients with pacing-induced cardiomyopathy: an UPGRADE post hoc analysis

Wilfried Schgoer

Papers

Heart failure medication and its effect on response to cardiac resynchronisation therapy in patients with pacing-induced cardiomyopathy: an UPGRADE post hoc analysis