Niacin...and statins

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme involved in the metabolism of Low-density lipoprotein (LDL) to pro-inflammatory mediators. 

Lp-PLA2 is highly expressed in the necrotic core of atherosclerotic plaques and has been associated with atherosclerotic plaque instability. 

Multiple studies have shown an association between elevated Lp-PLA2 levels and risk of both stroke and myocardial infarction, even after adjustment for standard vascular risk factors, and several professional organizations have recommended Lp-PLA2 as a potentially usefully tool to improve risk stratification for individual patients. 

Therapies directed at lowering Lp-PLA2 levels may represent a novel approach to reducing vascular risk, though direct clinical benefit from targeting treatment to Lp-PLA2 levels remains unproven. Statins appear to significantly lower Lp-PLA2 levels; fibrates and niacin may also lower Lp-PLA2 levels, though this is less well established. Darapladib, a potent, selective Lp-PLA2 inhibitor, is currently in phase III trials for prevention of recurrent vascular events in patients with coronary artery disease.

Full study

Lifestyle

Diets high in saturated fat and physical inactivity are associated with elevated levels of Lp-PLA2 and RANTES (). There have been limited studies focused on the effects of dietary factors and physical activity or exercise on Lp-PLA2 and RANTES. The general consensus is that dietary and lifestyle factors that reduce LDL-cholesterol likely result in Lp-PLA2 reduction (). In contrast, it remains unclear if similar diet and physical activity modifications would reduce RANTES levels; however, Garcia et al., () showed that single session of moderate intensity exercise (70% VO2max) for one hour can decrease RANTES levels in sedentary women

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Wholegrain and legumes

To determine dietary effects on circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and enzyme activity in peripheral blood mononuclear cells (PBMCs), 99 patients with impaired fasting glucose, impaired glucose tolerance, or newly-diagnosed T2D were randomly assigned to either a control group (usual diet with refined rice) or the whole grain and legume group. 

Substitution of whole grains and legumes for refined rice was associated with the replacement of 7% of energy from carbohydrates with energy from protein (about 4%) and fat. 

After 12 weeks, the whole grain and legume group showed a significant decrease in fasting glucose, insulin, homeostasis model assessment-insulin resistance, hemoglobin A1c, malondialdehyde, plasma Lp-PLA2 activity, and oxidized LDL (ox-LDL), and an increase in LDL particle size. 

The changes (Δs) in these variables in the whole grain and legume group were significantly different from those in controls after adjustment for the baseline levels. When all subjects were considered, Δ plasma Lp-PLA2 positively correlated with Δ glucose, Δ PBMC Lp-PLA2, Δ ox-LDL, and Δ urinary 8-epi-prostaglandin F after being adjusted for confounding factors. The Δ PBMC Lp-PLA2 correlated positively with Δ glucose and Δ ox-LDL, and negatively with Δ LDL particle size and baseline PBMC Lp-PLA2

The substitution of whole grains and legumes for refined rice resulted in a reduction in Lp-PLA2 activities in plasma and PBMCs partly through improved glycemic control, increased consumption of protein relative to carbohydrate, and reduced lipid peroxides

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Gum Disease

 Gum disease has been linked to hardening of the arteries for nearly a decade, and scientists have long fingered a gang of oral bacteria as the obvious suspects behind many cases of the vessel-clogging killer.
Now University of Florida researchers have cornered the bacterial ringleaders of gum disease inside human artery-clogging plaque — the first concrete evidence to place the pathogens at the heart of the circulatory crime scene. Their report appears in the current issue of Atherosclerosis, Thrombosis and Vascular Biology.

Metabolic Syndrome and Changes in Body Fat From a Low-fat Diet and/or Exercise Randomized Controlled Trial

It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight-stable randomized controlled trial of low-fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) were randomized into a 1-year, weight-stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (ΔMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (ΔBF) as a covariate. In men, ΔMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, ΔMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for ΔBF, all differences between groups were attenuated and no longer significant. ΔMetS were associated with ΔBF for both men (P < 0.0001) and women (P = 0.004). 

After adjustment for ΔBF, low-fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low-fat diet and/or increased physical activity appears to be body fat loss.

Diet, Exercise and the Metabolic Syndrome

The metabolic syndrome is a combination of metabolic disorders, such as dyslipidemia, hypertension, impaired glucose tolerance, compensatory hyperinsulinemia and the tendency to develop fat around the abdomen. Individuals with the metabolic syndrome are at high risk for atherosclerosis and, consequently, cardiovascular disease. However, as a result of several epidemiologic studies and some clinical trials, it has been suggested that people with the metabolic syndrome may benefit from intensive lifestyle modifications including dietary changes and adopting a physically more active lifestyle. In this review we summarize the effects of diet and physical activity on the development of the metabolic syndrome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1783583/

It is time to stop counting calories, and time instead to promote dietary changes that substantially and rapidly reduce cardiovascular morbidity and mortality

Most heart attacks and ischaemic strokes are caused by complicated atheroma usually compounded by thrombosis suddenly reducing blood flow in a critical artery. Extensive evidence suggests that this atheroma silently builds up over many decades. However, arterial stiffening can be seen even in children who are obese, and aortic fatty streaks are visible in some teenagers and young adults.1 Yet, most cardiovascular events do not manifest until after the age of 60 years. The general perception is thus of a slow process that will therefore only reverse slowly, if at all. However, this perception is wrong. Extensive empirical and trial evidence reveals that substantial reductions in mortality can occur within months of quitting smoking, or making healthy dietary changes. These reductions apply to both individuals and to entire populations. In one American hospital, admissions for acute coronary syndromes decreased by 40% within 6 months of the introduction of local smoke free legislation.2 When the law was rescinded, coronary admissions rapidly returned to previous levels. The introduction of smoke-free legislation in Scotland in 2006 was soon followed by a 6% decrease in out of hospital cardiac deaths and a 17% decrease in hospital admissions within a year.3Even 30 min of secondhand smoke exposure has been proven to increase platelet activity and hence elevate cardiovascular risk.4
Similarly, changes in diet can rapidly improve outcomes of cardiovascular disease (CVD), as demonstrated by several randomised trials. In the DART trial, 2033 survivors of myocardial infarction who were advised to eat fatty fish had a significant 29% reduction in all-cause mortality compared with control patients, with survival curves separating within months. Likewise, in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarcto Miocardico (GISSI)-Prevention trial, 1 g of Ω-3 fatty acids significantly reduced all-cause mortality and cardiovascular mortality in 11 324 myocardial infarction survivors. Moreover, survival curves separated early, with a significant reduction in total mortality after just 3 months of treatment (p=0.037).5
The PREvencion con DIeta MEDiterranea (PREDIMED) primary prevention randomised controlled trial found that an energy unrestricted diet supplemented with extra virgin olive oil or nuts achieved an impressive 30% reduction in major cardiovascular events (NNT=61) in over 7500 high risk individuals initially free of CVD. This reduction occurred within 3 months.6 Furthermore, this solid RCT evidence builds on a wealth of existing data from observational, cohort and secondary prevention intervention studies.7 ,8 It also provides further strong causal evidence that simple diet interventions can rapidly and powerfully reduce CVD outcomes. In comparison with an American Heart Association recommended ‘low fat’ diet, a Mediterranean diet post myocardial infarction is a more powerful coronary intervention tool for mortality than aspirin, statins, or coronary stents, but without any significant difference in total cholesterol, triglycerides or HDL between the two groups.9 It is the abundant α-linoleic acid, polyphenols and Ω-3 fatty acids found in nuts, olive oil, oily fish and vegetables, that rapidly exert positive health effects by attenuating inflammation, atherosclerosis and thrombosis.10 Conversely, the consumption of trans-fats commonly found in fast food can rapidly increase C reactive protein and other inflammatory markers within weeks.11
Strategies that prevent excessive weight gain in children and adults through curbing the consumption of the amounts of unhealthful foods should also be welcomed. However, simply focusing on weight loss in obese subjects misses a key finding from analysis of PREDIMED subgroups: dietary intervention achieved consistently large reductions in CVD risk irrespective of weight. Furthermore, weight loss interventions are rarely sustained. The weight loss industry, which emphasises calorie restriction over good nutrition, generates $58 billion in revenue annually in the USA, even though long-term follow-up studies reveal that the majority of individuals regain virtually all of the weight that was lost during treatment irrespective of whether they maintain their diet or exercise programme.12 Shifting focus away from calories and emphasising a dietary pattern that focuses on food quality rather than quantity will help to rapidly reduce obesity, related diseases and cardiovascular risk.13 ,14 Rapid weight loss and regain that can occur from fad dieting is actually detrimental to health. Such ‘weight cycling’ contributes to hypertension, insulin resistance and dyslipidaemia resulting in increased mortality risk and worse cardiovascular outcomes.15 The look AHEAD (Action for Health in Diabetes) trial found no reduction in the composite endpoint (ie, death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, or hospitalisation for angina) with a low calorie diet (on top of increased physical activity) in patients with type 2 diabetes despite a maximum follow-up of 13.5 years and despite significant weight loss in the intervention group.