Association of low-grade inflammation and elevated remnant cholesterol with risk of ASCVD and mortality in impaired renal function.

Background And Aims: Low-grade inflammation and elevated remnant cholesterol are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality. We hypothesized that each confers risk of myocardial infarction, ASCVD, and all-cause mortality in individuals with impaired renal function.

Methods: We included 102 906 individuals from the Copenhagen General Population Study, of which 9 935 had impaired renal function with estimated glomerular filtration rate <60 mL/min/1.

Remnant Cholesterol: Should it be a Target for Prevention of ASCVD?

Purpose Of Review: To summarize studies analyzing whether remnant cholesterol should be a target for prevention of atherosclerotic cardiovascular disease (ASCVD).

Recent Findings: There is a growing body of evidence from epidemiologic and Mendelian randomization studies implicating remnant cholesterol as a causal risk factor for ASCVD. However, the results of randomized controlled trials, particularly those conducted in the current high-intensity statin era, have been inconsistent.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

Background: The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH.

Methods And Results: This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis).

Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial.

Background And Aims: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial.

Methods: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design.

Remnant cholesterol and low-grade inflammation jointly in atherosclerotic cardiovascular disease: implications for clinical trials.

Purpose Of Review: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death despite the development of effective treatments. Recently, elevated remnant cholesterol and low-grade inflammation have emerged as factors explaining part of the residual ASCVD risk. Interestingly, the coexistence of both high remnant cholesterol and low-grade inflammation can further increase the risk of ASCVD.

Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

Aim: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction.

Lipoproteins, Cholesterol, and Atherosclerotic Cardiovascular Disease in East Asians and Europeans.

One fifth of the world population live in East Asia comprising Japan, Korea, and China where ischemic heart disease, a major component of atherosclerotic cardiovascular disease (ASCVD), is the second most frequent cause of death. Each of low-density lipoproteins (LDL), remnant lipoproteins, and lipoprotein(a), summarized as non-high-density lipoproteins (non-HDL) or apolipoprotein B (apoB) containing lipoproteins, causes ASCVD. However, a significant proportion of the evidence on lipoproteins and lipoprotein cholesterol with risk of ASCVD came from White people mainly living in Europe and North America and not from people living in East Asia or of East Asian descent.

Dual elevated remnant cholesterol and C-reactive protein in myocardial infarction, atherosclerotic cardiovascular disease, and mortality.

Background And Aims: Elevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both factors confers the highest risk. We tested the hypothesis that dual elevated remnant cholesterol and low-grade inflammation marked by elevated C-reactive protein is associated with the highest risk of myocardial infarction, ASCVD, and all-cause mortality.

Methods: The Copenhagen General Population Study randomly recruited white Danish individuals aged 20-100 years in 2003-2015 and followed them for a median 9.

Can remnant cholesterol (triglyceride-rich lipoproteins) reclassify estimated risk of atherosclerotic cardiovascular disease?

Purpose Of Review: To summarize recent studies analyzing reclassification of estimated risk of myocardial infarction (MI) and ischemic heart disease (IHD) by inclusion of remnant cholesterol (= cholesterol content in triglyceride-rich lipoproteins) in primary and secondary prevention settings.

Recent Findings: For individuals in a primary prevention setting with remnant cholesterol levels at least 95th percentile (≥1.6 mmol/l, 61 mg/dl), 23% of MI and 21% of IHD events developed later were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly.

Characterization of Polyvascular Disease in Heterozygous Familial Hypercholesterolemia: Its Association With Circulating Lipoprotein(a) Levels.

Background Heterozygous familial hypercholesterolemia (HeFH) more likely exhibits extensive atherosclerotic disease at multiple vascular beds. Lipoprotein(a) (Lp(a)) is an atherogenic lipoprotein that elevates HeFH-related atherosclerotic cardiovascular disease risks. Whether circulating Lp(a) level associates with polyvascular propagation of atherosclerosis in subjects with HeFH remains uncertain.

Elevated Remnant Cholesterol Reclassifies Risk of Ischemic Heart Disease and Myocardial Infarction.

Background: Elevated remnant cholesterol causes ischemic heart disease.

Objectives: We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.

Methods: For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use.

How Can We Identify Very High-Risk Heterozygous Familial Hypercholesterolemia?

Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder that elevates low-density lipoprotein cholesterol and increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). However, despite their atherogenic lipid profiles, the cardiovascular risk of HeFH varies in each individual. Their variety of phenotypic features suggests the need for better risk stratification to optimize their therapeutic management.

Substantially Elevated Atherosclerotic Risks in Japanese Severe Familial Hypercholesterolemia Defined by the International Atherosclerosis Society.

Background: The International Atherosclerosis Society (IAS) has proposed "severe familial hypercholesterolemia" (FH) as a phenotype with the highest cardiovascular risk. However, whether this criteria could appropriately stratify a high-risk Japanese patient with FH remains unknown.

Objectives: This study sought to characterize atherosclerotic cardiovascular diseases in IAS-defined Japanese subjects with severe FH.

A possible explanation for the contrasting results of REDUCE-IT vs. STRENGTH: cohort study mimicking trial designs.

Aims: We tested the hypothesis that the contrasting results for the effect of high-dose, purified omega-3 fatty acids on the prevention of atherosclerotic cardiovascular disease (ASCVD) in two randomized trials, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) vs. Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridaemia (STRENGTH), can be explained by differences in the effect of active and comparator oils on lipid traits and C-reactive protein.

Methods And Results: In the Copenhagen General Population Study (CGPS) with 106 088 individuals, to mimic trial designs we analysed those who met key inclusion criteria in REDUCE-IT (n = 5684; ASCVD = 852) and STRENGTH (n = 6862; ASCVD = 697).

Mid-Right Coronary Artery Spasm Diagnosed by an Ergometrine Provocation Test Through a Saphenous Vein Graft.

Although coronary artery spasm is a cause of acute coronary syndrome (ACS), demonstration of its possible cause in patients with a history of coronary artery bypass grafting remains challenging. We report a case of ACS that successfully provoked coronary artery spasm by pharmacological testing through a saphenous vein graft. ().

Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention.

Background: There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI).

Method And Results: Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24 h before and 3 h, 6 h, 1 day, and 2 days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR.

The association between the extent of lipidic burden and delta-fractional flow reserve: analysis from coronary physiological and near-infrared spectroscopic measures.

Background: Vulnerable plaque features including lipidic plaque have been shown to affect fractional flow reserve (FFR). Given that formation and propagation of lipid plaque is accompanied by endothelial dysfunction which impairs vascular tone, the degree of lipidic burden may affect vasoreactivity during hyperemia, potentially leading to reduced FFR. Our aim is to elucidate the relationship of the extent of lipidic plaque burden with coronary physiological vasoreactivity measure.

The feasibility and limitation of coronary computed tomographic angiography imaging to identify coronary lipid-rich atheroma in vivo: Findings from near-infrared spectroscopy analysis.

Background: Coronary computed tomography angiography (CCTA) non-invasively visualizes lipid-rich plaque. However, this ability is not fully validated in vivo. The current study aimed to elucidate the association of CCTA features with near-infrared spectroscopy-derived lipidic plaque measure in patients with coronary artery disease.

Patients With and Gene Variants Experienced Higher Incidence of Cardiovascular Outcomes in Heterozygous Familial Hypercholesterolemia.

Background Patients with familial hypercholesterolemia who harbored both low-density lipoprotein receptor () and (proprotein convertase subtilisin/kexin type 9) gene variants exhibit severe phenotype associated with substantially high levels of low-density lipoprotein cholesterol. In this study, we investigated the cardiovascular outcomes in patients with both and gene variants. Methods and Results A total of 232 unrelated patients with and/or gene variants were stratified as follows: patients with and () gene variants, patients with gene variant, and patients with gene variant.

Cardiac outcomes in patients with acute coronary syndrome attributable to calcified nodule.

Background And Aims: Calcified nodule (CN) is an eruptive calcified mass causing acute coronary syndrome (ACS). Since coronary calcification is associated with an elevated cardiac event's risk, ACS attributable to CN may exhibit worse clinical outcome following percutaneous coronary intervention (PCI).

Methods: We retrospectively analyzed 657 ACS patients receiving PCI with newer-generation drug-eluting stent (DES) implantation under intravascular ultrasound (IVUS) guidance.

Diminished response to statins predicts the occurrence of heart failure after acute myocardial infarction.

Background: Lowering low-density lipoprotein cholesterol (LDL-C) levels using a statin is a cornerstone of preventive therapeutic management following acute myocardial infarction (AMI). In addition to its anti-atherosclerotic effects, recent studies reported a lower occurrence of heart failure (HF) under statin therapy. However, there is a wide variability in statin response.