Introduction: Guidelines of management of dyslipidemias and prevention of cardiovascular disease (CVD) are based on firm scientific evidence obtained by randomized controlled trials (RCTs). However... Show moreIntroduction: Guidelines of management of dyslipidemias and prevention of cardiovascular disease (CVD) are based on firm scientific evidence obtained by randomized controlled trials (RCTs). However, the role of elevated low-density lipoprotein-cholesterol (LDL-C)as a risk factor of CVD and therapies to lower LDL-C are frequently disputed by colleagues who disagree with the conclusions of the RCTs published. This review focuses on this dispute, and evaluates the current approach of management of dyslipidemias and CVD prevention to find modern alternatives for more precise diagnosis and therapy of dyslipidemic patients.Areas covered: Recent interest in lipoprotein(a) (Lp(a)) and remnants lipoproteins and in therapies that do not influence LDL-C levels primarily, such as anti-inflammatory drugs and icosapent ethyl, has revitalized our concern to optimize the care for patients with increased CVD risk without focusing simply on reduction of LDL-C by therapy with statins, ezitemibe, and proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitors.Expert opinion: The limited characterization of study populations by measurement of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG) followed by measurement or calculation of LDL-C should be extended by a more integral approach in order to realize precision diagnostics and precision medicine, for the sake of personalized patient care. Show less
Orsi, F.A.; Lijfering, W.M.; Laarse, A. van der; Ruhaak, L.R.; Rosendaal, F.R.; Cannegieter, S.C.; Cobbaert, C. 2019
IntroductionThe current way to assess the risk of cardiovascular disease (CVD) is to measure conventional lipid and lipoprotein cholesterol fractions. Despite the success of statin treatment,... Show moreIntroductionThe current way to assess the risk of cardiovascular disease (CVD) is to measure conventional lipid and lipoprotein cholesterol fractions. Despite the success of statin treatment, residual cardiovascular risk remains high. Therefore, the value of extensive serum apolipoprotein (apo) profiling to assess the risk of ST-segment elevation myocardial infarction (STEMI) and of major adverse cardiac events (MACE) in patients with STEMI was investigated in a case-control design.Methods and resultsSerum apo levels were measured using liquid chromatography and mass spectrometry in 299 healthy individuals and 220 patients with STEMI. First, the association of apo profiles in baseline samples with risk of STEMI was examined, and second, the association of apo profiles at baseline with risk of recurrent MACE in patients with STEMI in a longitudinal study design was studied. High baseline (>1.25g/L) apoA1 levels were associated with a decreased risk of STEMI [odds ratio (OR) 0.17; 95% CI 0.11-0.26], whereas high apoB (>1.00g/L) levels (OR 2.17; 95% CI 1.40-3.36) and apoB/apoA1 ratio (OR per 1 SD (OR/SD): 2.16; 95% CI 1.76-2.65) were associated with an increased risk. Very-low-density-lipoprotein (VLDL)-associated apos gave conflicting results. Neither conventional lipid levels nor apo levels were associated with MACE in the STEMI group.ConclusionIn conclusion, apoA1, apoB, and apoB/apoA1 were strongly associated with risk of STEMI. No clear relation between VLDL-associated apos and the risk of STEMI was found. Neither baseline serum apos nor lipids predicted MACE in statin-treated patients during long-term follow-up after a first STEMI. Show less
Orsi, F.A.; Lijfering, W.M.; Laarse, A. van der; Ruhaak, L.R.; Rosendaal, F.R.; Cannegieter, S.C.; Cobbaert, C. 2019
Purpose: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterialthrombotic diseases. We investigated whether these apolipoproteins have prothromboticproperties and are... Show morePurpose: Apolipoproteins C-I, C-II, C-III and E have been associated with risk of arterialthrombotic diseases. We investigated whether these apolipoproteins have prothromboticproperties and are associated with risk of venous thromboembolism (VTE).Patients and methods: A total of 127 VTE patients and 299 controls were randomlyselected from the Multiple Environmental and Genetic Assessment of Risk Factors forVenous Thrombosis study (1999–2004), in the Netherlands. The apolipoproteins were quan-tified using mass spectrometry (LC/MS/MS), and their levels were analyzed as continuousvariable (per SD increase).Results: In controls, increases in levels of apolipoproteins were associated with increases inlevels of vitamin K-dependent factors, factor XI, antithrombin and clot lysis time.Additionally, increasing apolipoproteins C-III and E levels were associated with higherfactor VIII and von Willebrand factor levels. Levels of C-reactive protein were not associatedwith any apolipoprotein. The age- and sex-adjusted odds ratios of apolipoproteins E, C-III,CII and CI to the risk of venous thrombosis were 1.21 (95% CI, 0.98–1.49), 1.19 (95% CI,0.99–1.44), 1.24 (95% CI, 0.95–1.61) and 1.06 (95% CI, 0.87–1.30) per SD increase,respectively. These odds ratios did not attenuate after adjustments for statin use, estrogenuse, BMI, alcohol use, and self-reported diabetes.Conclusions: Levels of apolipoproteins C-I, C-II, C-III and E are associated with those ofseveral coagulation factors. However, whether these apolipoproteins are also associated withan increased risk of VTE remains to be established.Keywords: thrombosis, proteomics, lipids, cholesterol, coagulation, risk factors Show less
Ruhaak, L.R.; Romijn, F.P.H.T.M.; Smit, N.P.M.; Laarse, A. van der; Pieterse, M.M.; Maat, M.P.M. de; ... ; Cobbaert, C.M. 2018