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Residual Risk
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Mendelian randomization study supports a causal effect of triglycerides in coronary heart disease risk
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Lipoprotein(a): overlooked component of residual cardiovascular risk?
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.
15 March 2014
Non-HDL-C and residual cardiovascular risk: the Lp(a) perspective
Prof. Jean Charles Fruchart, Prof. Jean Davignon, Prof. Michel Hermans
Prof. Jean Charles Fruchart, Prof. Jean Davignon, Prof. Michel Hermans
An Editorial from the R3i Trustees

Lipoprotein(a) [Lp(a)] has long been a contentious lipoprotein since its discovery 50 years ago. Structurally, this lipoprotein consists of a low-density lipoprotein (LDL) particle with a glycoprotein, apolipoprotein(a), covalently linked to the apolipoprotein B100 (apoB) moiety of LDL. While earlier studies were negative, recent seminal reports have unequivocally established Lp(a) as a causal and independent risk factor for cardiovascular (CV) disease, as highlighted by recent consensus. As statins have limited or negligible effect on Lp(a), it is therefore plausible that Lp(a) may be relevant to lipid-related residual CV risk.
R3i activities on Kyoto 2014 congress
MSDA Kyoto 2014: A highlight of R3i activities
In 2014, the Residual Risk Reduction Initiative (R3i), together with the Japan Atherosclerosis Society (JAS), Japan Diabetes Society (JDS) and Japan Society for the Study of Obesity (JASSO), welcome clinicians and researchers to Kyoto, Japan for the 9th Annual Metabolic Syndrome, type 2 Diabetes and Atherosclerosis (MSDA) Congress, 12-14 September, 2014.
• Peripheral microvascular dysfunction predicts residual vascular risk
A previous report by the Residual Risk Reduction Initiative (R3i) highlighted microvascular disease as a predictor of cardiovascular disease (CVD) risk.1 The hyperaemia index, assessed by peripheral artery tonometry, is a measure of microvascular dysfunction, with low levels indicative of impaired reactive hyperaemia. The current study investigated whether this variable (logarithmic transformed data) could be used to stratify for residual coronary risk. The study included 213 coronary artery disease patients on statin therapy (mean age 66.7 years, 74% male, mean LDL cholesterol 70 mg/dL). Over a median follow-up of 2.7 years, coronary events occurred in 4 (4.0%) patients with hyperaemia index = 0.5) versus 18 (15.8%) patients with an index < 0.54 (p = 0.006). Cox regression analysis showed that the hyperaemia index was an independent predictor for coronary events even after adjustment for traditional risk factors, as well as estimated glomerular filtration rate (Hazard ratio 0.79, 95% confidence interval 0.66-0.95, p=0.012). In conclusion, the authors suggest that approaches aimed at improving microvascular dysfunction may offer potential to reduce residual risk in patients with coronary heart disease.
1. Rosenson RS, Fioretto P, Dodson PM. Does microvascular disease predict macrovascular events in type 2 diabetes? Atherosclerosis 2011;218:13-8.
Peripheral microvascular dysfunction predicts residual risk in coronary artery disease patients on statin therapy.
Matsue Y, Yoshida K, Nagahori W, Ohno M, Suzuki M, Matsumura A, Hashimoto Y, Yoshida M.
• DYSIS-Middle East: High prevalence of atherogenic dyslipidaemia in statin-treated patients
DYSIS-Middle East, part of the main DYSIS (Dyslipidemia International Study) trial, enrolled 2,182 patients (=45 years) on statin treatment (=3 months) in the United Arab Emirates, Saudi Arabia, Lebanon and Jordan. Most (83%) were classified as being at very high risk of cardiovascular events. Despite statin treatment, only 62% of patients attained guideline-recommended targets for low-density lipoprotein (LDL) cholesterol, and 56% and 49% attained desirable levels for high-density lipoprotein (HDL) cholesterol and triglycerides, respectively. This study highlights the high prevalence of lipid abnormalities among statin-treated patients in this region. Notably, atherogenic dyslipidaemia, i.e. elevated triglycerides with or without low HDL cholesterol, was present in about 50% of patients, indicating the need for improved clinical management.
Results of the Dyslipidemia International Study (DYSIS)-Middle East: Clinical perspective on the prevalence and characteristics of lipid abnormalities in the setting of chronic statin treatment.
Al Sifri SN, Almahmeed W, Azar S, Okkeh O, Bramlage P, Jünger C, Halawa, Ambegaonkar B, Wajih S, Brudi P.
• High triglyceride/HDL-C ratio predicts CVD in US population
Both high triglycerides (TG) and a low plasma concentration of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk for coronary heart disease (CHD). The ratio of TG/HDL-C is also predictive of residual risk for CHD and poorer metabolic control in people with type 2 diabetes. This survival analysis (n=39,447 men) evaluated the potential of the TG/HDL-C ratio (cut-point 3.5), as a predictor for CHD, cardiovascular disease (CVD) and all-cause mortality. The total follow-up was 581,194 person-years. The TG/HDL-C ratio predicted CHD, CVD, and all-cause mortality after adjustment for established risk factors and non-HDL-C. These data reaffirm the role of atherogenic dyslipidaemia as a marker of residual coronary risk.
Triglyceride-to-High-Density-Lipoprotein-Cholesterol Ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men.
Vega GL, Barlow CE, Grundy SM, Leonard D, Defina LF.
• High TG/HDL-C ratio is associated with risk of CKD in the Japanese population
As shown by the REALIST-Micro STUDY,1 elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are robustly associated with diabetic kidney disease in patients with type 2 diabetes and controlled low-density lipoprotein cholesterol (LDL-C) levels.1 This cross-sectional study (n=216,007 Japanese adults, 88,516 men 127,491 women) used TG/HDL-C quartile analysis to assess the association with chronic kidney disease (CKD). The TG/HDL-C quartiles were <1.26, 1.26-1.98, 1.99-3.18 and >3.18 in men; <0.96, 0.96-1.44, 1.45-2.22, and >2.22 in women). Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 (low eGFR) and/or proteinuria (defined as urinary protein =1+ on dipstick testing)]. In both men and women, the prevalence of CKD, low eGFR, and proteinuria increased significantly with increasing quartiles of TG/HDL-C (p for trend <0.001). Compared with those in the lowest quartile, subjects in the highest quartile of TG/HDL-C had a significantly greater risk of CKD (adjusted odds ratio: 1.57, 95% confidence interval 1.49-1.65 in men; and 1.41, 1.34-1.48 in women). The increase in risk of CKD with TG/HDL-C was evident irrespective of the presence or absence of hypertension, diabetes and obesity. In conclusion, this analysis of more than 200,000 Japanese men and women reaffirms the link between triglycerides and HDL-C and risk for CKD.
1. Sacks FM, Hermans MP, Fioretto P et al. Association between plasma triglycerides and HDL-cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes: A global case-control study in 13 countries. Circulation 2013 Dec 18. [Epub ahead of print].
Association of the triglycerides to high-density lipoprotein cholesterol ratio with the risk of chronic kidney disease: Analysis in a large Japanese population.
Tsuruya K, Yoshida H, Nagata M, Kitazono T, Hirakata H, Iseki K, Moriyama T, Yamagata K, Yoshida H, Fujimoto S, Asahi K, Kurahashi I, Ohashi Y, Watanabe T.
• Atherogenic dyslipidaemia linked with hepatic steatosis
This study adds to evidence linking hepatic steatosis with atherogenic dyslipidaemia and resultant increased cardiovascular risk. In total, 6,333 asymptomatic subjects without clinical cardiovascular disease in Brazil were included over the period 2008 to 2010. Hepatic steatosis was diagnosed by ultrasound. Atherogenic dyslipidaemia was defined using 2 definitions: i) criteria for metabolic syndrome or ii) insulin resistance (triglyceride/high-density-lipoprotein (HDL) cholesterol ratio of =2.5 in women and =3.5 in men). Hepatic steatosis was detected in 36% of the sample (mean age 43.5 years, 79% men, average body mass index 26.3 kg/m2). While plasma levels of low-density-lipoprotein (LDL) cholesterol were similar in subjects with and without hepatic steatosis, HDL cholesterol was lower and triglycerides were higher in subjects with steatosis. After multivariate adjustment, hepatic steatosis was significantly and independently associated with atherogenic dyslipidaemia for both definitions: i) odds ratio 2.47, 95% confidence interval [CI] 2.03 to 3.02, and for ii) odds ratio 2.50, 95% confidence interval 2.13 to 2.91). The association between hepatic steatosis and atherogenic dyslipidaemia was independent of obesity, physical activity, hyperglycaemia, and systemic inflammation. This study suggests potential for atherogenic dyslipidaemia as a target of interest for therapeutic intervention in non-alcoholic fatty liver disease/steatosis.
Relation of hepatic steatosis to atherogenic dyslipidemia.
Makadia SS, Blaha M, Keenan T, Ndumele C, Jones S, DeFilippis A, Martin S, Kohli P, Conceicao R, Carvalho J, Nasir K, Blumenthal R, Santos RD