Landmark study
A higher TG/HDL-C ratio increases the incidence and progression of chronic kidney disease
Focus on...
Triglyceride-rich lipoprotein cholesterol: how to calculate from nonfasting samples?
The National Lipid Association (NLA)
The National Lipid Association (NLA) is a nonprofit, multidisciplinary medical society focused on enhancing the practice of lipid management in clinical medicine.
MSDA 2015 Congress
4 September 2015

Back to basics: triglyceride-rich lipoproteins, remnants and residual vascular risk

Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
Prof. Jean Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco
An Editorial from the R3i Trustees

This month we focus on triglyceride-rich lipoproteins (TRLs) as a contributor to lipid-related residual vascular risk. These TRLs are comprised of intestinally-derived chylomicrons remnants, and very-low-density lipoprotein (VLDL) and VLDL remnants. It is important to emphasise that triglycerides contained within TRLs are not atherogenic; instead it is the cholesterol component of TRLs that is atherogenic.
R3i Education Channel

Resistin: a novel marker of residual vascular risk in statin-treated patients

According to this report from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE-IT TIMI) 22 group, the adipokine resistin is a marker of residual cardiovascular risk in patients hospitalised with a recurrent acute coronary syndrome. This nested case-control cohort of statin-treated patients in the PROVE-IT TIMI 22 study measured plasma levels of resistin and leptin in 176 cases with coronary death, myocardial infarction, or unstable angina pectoris during follow-up, matched 1:1 to 176 controls. In logistic regression analysis adjusted for additional risk factors including high-sensitivity C-reactive protein and history of diabetes, on-statin resistin levels were associated with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval 1.04 to 4.19). There was, however, no association between circulating leptin levels and recurrent coronary events. These findings suggest potential for other biomarkers, beyond lipids, in residual vascular risk.
On-statin resistin, leptin, and risk of recurrent coronary events after hospitalization for an acute coronary syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study)
Khera AV, Qamar A, Murphy SA et al.

New meta-analysis shows PCSK9 monoclonal therapies are safe and effective

In this meta-analysis of more than 12,200 patients in 25 randomised controlled trials, the PCSK9 inhibitors evolocumab and alirocumab were shown to be well tolerated, lowering low-density lipoprotein (LDL) cholesterol by 50-55%. Evolocumab has now been approved for use in Europe; alirocumab is approved by the US Food and Drug Administration (FDA) and has also received a favourable response from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicine Agency (EMA). Alirocumab was associated with an increased rate of injection-site reactions (relative risk [RR] 1.48, 95 % CI: 1.05 to 2.09, p = 0.02); and evolocumab was associated with reduced rates of abnormal liver function (RR 0.43, 95 % CI: 0.20 to 0.93, p = 0.03) compared with placebo. Both evolocumab and alirocumab significantly reduced LDL cholesterol (by 54.6%, 95% CI 58.7 to 50.5% for evolocumab, 52.6%, 95% CI: -58.2 to -47.0% for alirocumab) versus placebo, and increased high-density lipoprotein cholesterol (by 6-8%) These findings reaffirm the efficacy and safety profiles of these novel therapies previously observed in individual studies.
Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials.
Zhang XL, Zhu QQ, Zhu L et al

Low HDL-C plus elevated CRP levels predict worse outcome following PCI

Coronary artery disease (CAD) is an inflammatory state which has been shown to adversely affect the biological function of high-density lipoproteins (HDL). This study investigated the interaction between HDL cholesterol (HDL-C) and C-reactive protein (CRP) in CAD patients undergoing first percutaneous coronary intervention (PCI). Of 3,507 consecutive patients undergoing PCI, 1,682 patients (48%) had been treated with statin at this time. This group were stratified by HDL-C levels (cutoffs of 40 (1.03 mmol/L) for men and 50 mg/dL (1.29 mmol/L) for women, respectively) and a CRP cutoff of 2 mg/dL into four groups: 1) high HDL-C/low CRP, 2) high HDL-C/high CRP, 3) low HDL-C/low CRP, and 4) low HDL-C/high CRP. Over a median follow-up of 1,985 days, 197 (11.7%) patients died due to cardiac death (n=58), carcinoma (n=61), stroke (n=10) and other causes (n=69). Multivariate Cox hazard regression analyses showed that the group with low HDL-C and high CRP had a significantly higher rate of all-cause death even after adjustment for other covariates (hazard ratio 2.38, 1.59-3.61, p<0.0001). The authors highlight the combination of low HDL-C and elevated CRP as predictive of worse long-term outcome after PCI in statin-treated CAD patients.
Impact of combined C-Reactive Protein and High-Density Lipoprotein Cholesterol levels on long-term outcomes in patients with coronary artery disease after a first percutaneous coronary intervention.
Ogita M, Miyauchi K, Tsuboi S et al

Dyslipidaemia and diabetic macular oedema: is there more than meets the eye?

The link between lipid levels and diabetic macular oedema (DME) warrants further investigation, according to this systematic review and meta-analysis. The authors identified 21 studies reporting on the relationship between blood lipid levels and DME (5 cross-sectional, 5 cohort, 7 case-control, and 4 randomised controlled studies). Meta-analysis of case-control studies showed that mean total serum cholesterol (p<0.001), low-density lipoprotein cholesterol (p<0.05), and serum triglycerides (p<0.05) were significantly higher in patients with DME than in those without DME. However, meta-analysis of prospective randomised controlled trials did not show significant increased risk of worsening of hard exudates and severity of DME in patients treated with lipid-modifying agents compared with placebo. Given the significant public health relevance, further investigation of these discrepancies is warranted.
Dyslipidemia and diabetic macular edema: a systematic review and meta-analysis
Das R, Kerr R, Chakravarthy U, Hogg RE

**News from American Diabetes Association's Scientific Sessions, June 5 - 9, 2015, Boston, Massachusetts**

Data from the European Study on Cardiovascular Risk Prevention and Management in Daily Practice (EURIKA, NCT00882336) highlighted the prevalence of atherogenic dyslipidaemia (elevated triglycerides [TG] with/without low high-density lipoprotein cholesterol [HDL-C]), especially in diabetic patients on a statin. EURIKA was a cross-sectional study conducted in 12 European countries which recruited 7,641 patients aged ? 50 years (48% male, mean age 63.2 years), without clinical cardiovascular disease (CVD) but with at least one CVD risk factor. Elevated TG was defined as ?200 mg/dL (2.26 mmol/L) and low HDL-C was defined as <40 mg/dL (1.03 mmol/L) in men and <50 mg/dL (1.29 mmol/L) in women. In the overall population, the prevalence of elevated TG, low HDL-C and both were 20.8%, 22.1% and 9.9%, respectively. Less than 60% of diabetes patients were receiving lipid-modifying therapy. In patients with diabetes who were on a statin, 27.9% had elevated TG, 29.8% had low HDL-C, and 14.6% had both. These data highlight the unmet clinical need for improved management of atherogenic dyslipidaemia in primary prevention patients, especially those with diabetes.
Treatment of patients with elevated triglycerides and low HDL-C in Europe: Results from EURIKA.
Halcox JP, Pasquet B, Hendriksson KM
Abstract 695-P

Atherogenic dyslipidaemia more prevalent in type 2 diabetes ‘Night owls’

Patients with type 2 diabetes and an evening chronotype (so-called ‘night owls’) have a higher prevalence of atherogenic dyslipidaemia and poorer glycaemic control, but a markedly lower prevalence of cerebrovascular disease. In this study, 454 patients with type 2 diabetes (mean age 66 years; mean diabetes duration 16 years), were categorised by chronotype based on self-reported mid-sleep time (i.e. the midpoint between sleep onset and wake time) on weekends. Patients with an evening chronotype had significantly worse metabolic control than morning chronotypes, as characterised by HbA1c (mean [SD] 59[10] vs. 57[10] mmol/mol, p 0.0388), and an increased prevalence of atherogenic dyslipidaemia (56% vs. 42%, p 0.0028). The ratio of log[TG/HDL-C] was also higher in evening compared with morning chronotypes (mean [SD] 0.50[0.34] vs. 0.43[0.34], p 0.0335). However, the prevalence of transient ischaemic attack/stroke was higher in morning than evening chronotypes (11% vs. 3%, p 0.0066). There were no significant differences between the two groups with respect to other characteristics.
Evening chronotype in T2DM linked to atherogenic dyslipidemia and lower prevalence of cerebrovascular disease.
Hermans MP, Camara S, Ahn SA, Rousseau MF
Abstract 702-P.