Residual Cardiovascular Risk Factors in Dyslipidemia

Cardiovascular disease poses a major challenge for the 21st century. Although good control of blood pressure and type 2 diabetes and reducing low-density lipoprotein-cholesterol levels can improve cardiovascular outcomes, a substantial residual risk remains existed after treatment in most patient populations. Recently, many efforts have been directed at finding the important role of low high-density-lipoprotein cholesterol, high triglycerides, especially triglyceride-rich lipoproteins and lipoprotein (a) in the metabolism of atherosclerotic plaque formation Therefore, based on the recent evidence, identification and treatment of these risk factors may play a role in optimizing therapeutic strategy, particularly in high risk subjects along with conventional treatment. In clinical practice, adequate attention should be paid when screening and managing residual cardiovascular risk factors in dyslipidemia in term of individualized approach. The ongoing trials will give more answers to elucidate this important area.

The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants—and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

Long-term residual cardiovascular risk after acute coronary syndrome: antithrombotic treatment options

The residual risk of patients surviving until 1 year after acute coronary syndromes (ACS) is still high, despite secondary prevention. The cornerstone of treatment of patients with ACS is dual antiplatelet therapy (DAPT) consisting of low-dose aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) for 12 months, or less in those patients at higher risk for bleeding. To reduce the residual risk beyond 1 year in those patients not at high bleeding risk who tolerated DAPT and did not suffer an (ischaemic or bleeding) event would intuitively mean to prolong DAPT. However, prolonged DAPT always comes at the cost of more bleeding. Therefore, assessing both ischaemic and bleeding risk in these patients at 1 year after ACS is crucial. In addition, another antithrombotic treatment consisting of low-dose rivaroxaban combined with low-dose aspirin has been shown to reduce ischaemic events. In this review, we describe residual thrombotic risk at 1 year after ACS, evaluate the evidence for antithrombotic options beyond 1 year and provide a practical guide to determine which patients would benefit the most from these therapies.

Evaluation of two highly effective lipid-lowering therapies in subjects with acute myocardial infarction

For cardiovascular disease prevention, statins alone or combined with ezetimibe have been recommended to achieve low-density lipoprotein cholesterol targets, but their effects on other lipids are less reported. This study was designed to examine lipid changes in subjects with ST-segment elevation myocardial infarction (STEMI) after two highly effective lipid-lowering therapies. Twenty patients with STEMI were randomized to be treated with rosuvastatin 20 mg QD or simvastatin 40 mg combined with ezetimibe 10 mg QD for 30 days. Fasting blood samples were collected on the first day (D1) and after 30 days (D30). Lipidomic analysis was performed using the Lipidyzer platform. Similar classic lipid profile was obtained in both groups of lipid-lowering therapies. However, differences with the lipidomic analysis were observed between D30 and D1 for most of the analyzed classes. Differences were noted with lipid-lowering therapies for lipids such as FA, LPC, PC, PE, CE, Cer, and SM, notably in patients treated with rosuvastatin. Correlation studies between classic lipid profiles and lipidomic results showed different information. These findings seem relevant, due to the involvement of these lipid classes in crucial mechanisms of atherosclerosis, and may account for residual cardiovascular risk.Randomized clinical trial: ClinicalTrials.gov, NCT02428374, registered on 28/09/2014.

Discordance between apolipoprotein B or non-HDL-cholesterol and LDL-cholesterol in middle-aged and elderly Chinese patients predicts arterial stiffness

Background Discordance of lipid parameters is closely associated with residual cardiovascular risk. This study investigated the discordance between non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) and low-density lipoprotein cholesterol (LDL-C), and assessed arterial stiffness risk. Methods This study included a total of 402 middle-aged and elderly Northern Chinese individuals whose brachial-ankle pulse wave conduction velocity (baPWV), and clinical and biochemical data were measured. Arterial stiffness was defined by inclusion in the upper quartile of the baPWV. All participants were divided into four mutually exclusive concordance/discordance groups based on the lipid goal for high-risk populations, according to the 2019 European Society of Cardiology / European Atherosclerosis Society guidelines. Discordance was defined as LDL-C ≥ 1.81 mmol/L with non-HDL-C < 2.59 mmol/L, or apoB < 0.80 mmol/L, or vice versa. Results The mean age of the participants was 65.9 ± 13.0 years; 59.5% of the participants were male. The mean LDL-C was 2.41 ± 0.81 mmol/L, non-HDL-C: 3.06 ± 0.94 mmol/L, and apoB: 0.84 ± 0.21 mmol/L. LDL-C was observed to be discordant with non-HDL-C (20.1%) and apoB (30.8%). When stratified according to LDL-C levels, the baPWV was greater in those patients with higher non-HDL-C or apoB levels. In the adjusted logistic regression model, low LDL-C and high non-HDL-C or apoB discordance were also associated with the risk of arterial stiffness (OR: 13.412 and OR: 13.054, respectively). Conclusions There was discordance between LDL-C and non-HDL-C, or apoB in middle-aged and elderly Chinese individuals; this was associated with a higher risk of arterial stiffness. Non-HDL-C or apoB levels could be used to identify individuals who may benefit from more comprehensive lipid modification.