Recent years have brought a significant amount of new results in the field of atherosclerosis. A better understanding of the role of different lipoprotein particles in the formation of atherosclerotic plaques is now possible. Recent cardiovascular clinical trials have also shed more light upon the efficacy and safety of novel compounds targeting the main pathways of atherosclerosis and its cardiovascular complications.In this review, we first provide a background consisting of the current understanding of the pathophysiology and treatment of atherosclerotic disease, followed by our future perspectives on several novel classes of drugs that target atherosclerosis. The focus of this update is on the pathophysiology and medical interventions of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)).
Introduction
The 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 results
Serum 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 (> 1.25 g/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 (> 1.00 g/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.
Conclusion
In 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.
Several modifiable cardiovascular risk factors are associated with carotid calcification growth, however, time and baseline calcification load remain the most important determinants of calcification development.
Introduction
To investigate the additive prognostic value of growth differentiation factor (GDF-15) levels in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneously coronary intervention (pPCI) with 10-year mortality on top of clinical characteristics and known cardiac biomarkers.
Methods
Baseline serum GDF-15 levels were measured in 290 STEMI patients treated with pPCI in the MISSION! intervention trial conducted from February 1, 2004 through October 31, 2006. The incremental prognostic value of GDF-15 and NTproBNP levels was evaluated on top of clinical characteristics using Cox proportional hazards analysis, Chi-square models and C-index. Outcome was 10-year all-cause mortality.
Results
Mean age was 59.0 ± 11.5 years and 65 (22.4) patients were female. A total of 37 patients died during a follow-up of 9.4 (IQR 8.8–10.0) years. Multivariable Cox regression revealed GDF-15 and NTproBNP levels above median to be independently associated with 10-year all-cause mortality [HR GDF-15, 2.453 (95% CI 1.064–5.658),
P
= 0.04; HR NTproBNP, 2.413 (95% CI 1.043–5.564),
P
= 0.04] after correction for other clinical variables. Stratified by median GDF-15 (37.78 pmol/L) and NTproBNP (11.74 pmol/L) levels, Kaplan–Meier curves showed significant better survival for patients with GDF-15 and NTproBNP levels below the median versus above the median. The likelihood ratio test showed a significant incremental value of GDF-15 (
P
= 0.03) as compared with a model with clinically important variables and NTproBNP. The C-statistics for this model improved from 0.82 to 0.84 when adding GDF-15.
Conclusion
GDF-15 levels at admission in STEMI patients are independently associated with 10-year all-cause mortality rates and could improve risk stratification on top of clinical variables and other cardiac biomarkers.
Electronic supplementary material
The online version of this article (10.1007/s40119-019-0127-4) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.