Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do not support Lp(a) as a risk factor for venous thrombotic events and impaired fibrinolysis. Very low Lp(a) levels may associate with increased risk of diabetes mellitus meriting further study. Lp(a) has pro-inflammatory and pro-atherosclerotic properties, which may partly relate to the oxidized phospholipids carried by Lp(a). This panel recommends testing Lp(a) concentration at least once in adults; cascade testing has potential value in familial hypercholesterolaemia, or with family or personal history of (very) high Lp(a) or premature ASCVD. Without specific Lp(a)-lowering therapies, early intensive risk factor management is recommended, targeted according to global cardiovascular risk and Lp(a) level. Lipoprotein apheresis is an option for very high Lp(a) with progressive cardiovascular disease despite optimal management of risk factors. In conclusion, this statement reinforces evidence for Lp(a) as a causal risk factor for cardiovascular outcomes. Trials of specific Lp(a)-lowering treatments are critical to confirm clinical benefit for cardiovascular disease and aortic valve stenosis

2017 Update of ESC/EAS Task Force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia

A correction has been published: European Heart Journal, Volume 39, Issue 22, 7 June 2018, Pages 2105Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017.info:eu-repo/semantics/publishedVersio

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM) paradigm : conceptual framework and therapeutic potential: A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARM) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARM agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARM agonist safely reduces residual cardiovascular risk.Peer reviewe

Residual vascular risk in diabetes – will the SPPARM alpha concept hold the key?

No abstract available

Aynı kardiyovasküler sonlanıma sahip ailevi hiperkolesterolemi ve yüksek lipoprotein (a) düzeyi olan tek yumurta ikizleri: Olgu sunumu ve literatürün gözden geçirilmesi

Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal dominant disease that leads to premature cardiovascular disease (CVD). Since monozygotic twins share the intrauterine environment and have the same age and gene profie, they could represent a very special resource for the investigation of the causes and the natural course of FH. This report is a description of 36-year-old monozygotic twin brothers with almost identical early coronary artery involvement due to FH concomitant with high lipoprotein(a) (Lpa) levels and a review of the literature. Sequence analysis revealed that the twins were homozygous for the LDLR c.1060+10G>A (rs12710260) mutation and heterozygous for the LDLR c.542C>T (rs557344672) mutations. Both were also homozygous for the c.1060+7T>C (rs2738442) and c.1586+53A>G (rs1569372) mutations in the LDLR gene as well as c.4265A>T (rs568413) mutations in the APOB gene. in the literature, there are 7 twin cases with reported FH, but none with high Lpa levels. the HoFH twins in this case report had lower low-density lipoprotein (LDL) cholesterol levels than expected (before treatment 204 and 223 mg/dL), with almost identical coronary involvement. Both had an extremely high Lpa level (308 and 272 nmol/L) with a very low coronary calcium score (16 AU) and a good response to statins (>60%). There was a history of the fist CVD event occurring at nearly the same age (32–34 years) in the family. This could be an important aspect of FH families as a result of the similar timing of cumulative LDL exposure exceeding the threshold of CVD events. in conclusion, this fist report of monozygotic HoFH twins with elevated Lpa levels and almost identical early coronary artery involvement at the same age provides evidence to substantiate the hypothesis of lifetime cholesterol burden/ exposure.Homozigot Ailevi hiperkolesterolemi (HoAH), erken kardiyovasküler hastalığa yol açan nadir, otozomal dominant bir hastalıktır. Monozigotik ikizler intrauterin çevreyi, yaşı ve tüm genlerini ortak paylaştıklarından, AH’nin nedenlerini ve doğal seyrini araştırmak için çok özel bir kaynağı temsil edebilirler. Bu yazıda AH ve yüksek lipoprotein a (Lpa) düzeylerine bağlı olarak hemen hemen aynı erken koroner arter tutulumu olan 36 yaşında monozigotik ikiz kardeşleri literatür derlemesi ile birlikte sunuyoruz. Dizi analizi ile ikizlerin LDLR c.1060+10G>A (rs12710260) mutasyonu için homozigot ve LDLR c.542C>T (rs557344672) mutasyonları için heterozigot olduğu gösterilmiştir. Her ikisi de LDLR genindeki c.1060+7T>C (rs2738442), c.1586+53A>G (rs1569372) mutasyonları ve APOB genindeki c.4265A>T (rs568413) mutasyonları için homozigottur. Literatürde AH için bildirilen toplam 7 ikiz vaka vardır ve hiç birinde yüksek Lpa düzeyleri bildirilmemiştir. HoAH olan ikizler, beklenenden daha düşük LDL seviyelerine sahipti (tedavi öncesi 204 ve 223 mg/dL) ve neredeyse aynı koroner tutulumu izlendi. Her ikisi de yüksek Lpa seviyeleri (308 ve 272 nmol/L) ve çok düşük koroner kalsiyum skoru (16 AU) na sahipti ve de statinlere iyi yanıt (>%60) verdiler. Ayrıca, ilk kardiyovasküler olayları ailede neredeyse aynı yaşlarda (yani 32–34 yaşlarında) meydana gelmişti. Bu, kardiyovasküler olay gelişimi eşiğini aşan kümülatif LDL maruziyetinin benzer zamanlaması nedeniyle AH ailelerinin önemli bir özelliği olabilir. Sonuç olarak, yüksek Lpa seviyeleri ve hemen hemen aynı erken koroner arter tutulumu olan monozigotik HoAH ikizler, ömür boyu kolesterol yükü / maruziyeti hipotezine doğrulayacı bir kanıt sayılabilir

Serum Pon-1 Activity but not Q192R Polymorphism is Related to The Extent of Atherosclerosis

Aim: Paraoxonase-1 (PON1) is an antioxidant enzyme located in high density lipoprotein (HDL). PON1 was defined as a protective factor against atherosclerosis. The aim of this study was to investigate the possible relationship between serum paraoxonase (PONase), homocysteine thiolactonase (HTase) activities and PON1 Q192R polymorphism, and the extent and severity of atherosclerosis. Methods: Blood specimens were collected from 142 individuals who had no coronary artery lesions angiographically (control group) and 128 individuals who had angiographically documented coronary artery disease of several degrees (patient group). The extent and severity of arterial lesions were evaluated by the Gensini scoring system. PONase and HTase activities were measured in serum using a spectrophotometric method. PON1 Q192R polymorphism was evaluated using PCR-RFLP after DNA isolation from blood. Results: Serum PONase and HTase activities were significantly lower in the patient group than in healthy controls (135.7 +/- 56.0 U/mL vs 153.8 +/- 62.0 U/mL, p < 0.05; 36.0 +/- 6.1 U/mL vs 43.0 +/- 4.04 U/mL, p < 0.01; respectively). In the patient group, there was a negative correlation between PONase, HTase activities and the Gensini score (r = -0.168, p = 0.039; r = -0.164, p = 0.006, respectively). In both groups, there was no significant difference in the distribution of PON1 Q192R polymorphism. In the patient group, the distribution of Gensini scores according to genotypes was not significant. Conclusion: It has been concluded that serum PONase and HTase activities might be a more relevant marker than PON1 genotype in evaluating the extent and severity of atherosclerosis.WoSScopu

Women, lipids, and atherosclerotic cardiovascular disease: a call to action from the European Atherosclerosis Society

Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women. [GRAPHICS]