[Hyperlipoproteinaemia(a) and stroke. A case report of a family with early-onset severe atherosclerotic disease]. / Hiperlipoproteinemia(a) e ictus. A propósito de una familia con enfermedad ateroesclerótica grave precoz.

TITLE: Hiperlipoproteinemia(a) e ictus. A propósito de una familia con enfermedad ateroesclerótica grave precoz.

Síndrome de quilomicronemia: aspectos genéticos y revisión de la literatura / Chylomicronemia syndrome: genetic aspects and literature review

Chylomicronemia syndrome is a metabolic condition characterized by severe hypertriglyceridemia and fasting chylomicronemia, secondary to an alteration in the ability to metabolize triglycerides. It can respond to different etiologies, the most frequent being multifactorial. Familial chylomicronemia syndrome, on the other hand, represents an infrequent cause of chylomicronemia syndrome, showing an autosomal recessive inheritance pattern. It's caused by pathogenic variants in genes related to chylomicron's metabolism, mainly LPL1 gene. One of the main associated risks is the occurrence of acute pancreatitis, which can also have a recurrent course. The primary therapy goal in patients with this condition is prevention of pancreatitis and related comorbidities. The treatment basis consists in reduce chylomicron formation by restriction of dietary fat, in association with physical activity and pharmacologic therapy. It is important to distinguish the etiology of chylomicronemia syndrome since it has repercussions in terms of response to treatment, complications, and recurrence risk. (AU)

Expert position statements: comparison of recommendations for the care of adults and youth with elevated lipoprotein(a).

PURPOSE OF REVIEW: Summarize recent recommendations on clinical management of adults and youth with elevated lipoprotein(a) [Lp(a)] who are at-risk of or affected by cardiovascular disease (CVD). RECENT FINDINGS: There is ample evidence to support elevated Lp(a) levels, present in approximately 20% of the general population, as a causal, independent risk factor for CVD and its role as a significant risk enhancer. Several guidelines and position statements have been published to assist in the identification, treatment and follow-up of adults with elevated levels of Lp(a). There is growing interest in Lp(a) screening and strategies to improve health behaviors starting in youth, although published recommendations for this population are limited. In addition to the well established increased risk of myocardial infarction, stroke and valvular aortic stenosis, data from the coronavirus pandemic suggest adults with elevated Lp(a) may have a particularly high-risk of cardiovascular complications. Lp(a)-specific-lowering therapies are currently in development. Despite their inability to lower Lp(a), use of statins have been shown to improve outcomes in primary and secondary prevention. SUMMARY: Considerable differences exist amongst published guidelines for adults on the use of Lp(a) in clinical practice, and recommendations for youth are limited. With increasing knowledge of Lp(a)'s role in CVD, including recent observations of COVID-19-related risk of cardiovascular complications, more harmonized and comprehensive guidelines for Lp(a) in clinical practice are required. This will facilitate clinical decision-making and help define best practices for identification and management of elevated Lp(a) in adults and youth.

The dedicated "Lp(a) clinic": A concept whose time has arrived?

The emergence of pathophysiological, epidemiologic, and genetic data strongly supports the causality for lipoprotein(a) [Lp(a)] in cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). In parallel, novel Lp(a) lowering approaches have been developed that have re-invigorated clinical interest in Lp(a). Because Lp(a) is the most prevalent monogenetic lipid disorder globally, with prevalence of Lp(a) > 50 mg/dL estimated at >1.4 billion people, the rationale for diagnosing and managing Lp(a)-mediated risk is now stronger than ever. Patients with elevated Lp(a) are significantly under-diagnosed and the diagnosis is frequently made ad hoc rather than systematically. Elevated Lp(a) levels are associated with atherothrombotic risk and patients present with varied clinical phenotypes, ranging from stroke in pediatric age groups, to ST-segment elevation myocardial infarction in young males, to CAVD in elderly individuals. A new clinical care paradigm of a dedicated "Lp(a) Clinic" would serve to evaluate and manage such patients who have elevated Lp(a) as the pathophysiological etiology. Such a clinic would include multidisciplinary expertise in lipid metabolism, clinical cardiology, vascular medicine, valvular disease, thrombosis, and pediatric aspects of clinical care. This viewpoint argues for the rationale of an Lp(a) outpatient clinic where patients with elevated Lp(a) and their affected relatives can be referred, evaluated, managed and followed, to ultimately reduce Lp(a)-mediated CVD and CAVD risk.

Lipemia retinalis in a 27 day old neonate: A case report.

Familial combined hyperlipidemia, which presents as hypercholesterolemia or hypertriglyceridemia, is the commonest form of genetic hyperlipidemia and is associated with premature coronary artery disease. This is a rare case report of a 27 day-old neonate born out of a third-degree consanguineous marriage, with grade III lipemia retinalis secondary to familial-combined hyperlipidemia.

Lipoprotein(a) in Patients Undergoing Transcatheter Aortic Valve Replacement.

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for calcific aortic valve stenosis (CAVS) for which transcatheter aortic valve replacement (TAVR) is increasingly utilized as treatment. We evaluated the effect of a program to increase testing of and define the prevalence of elevated Lp(a) among patients undergoing TAVR. Educational efforts and incorporation of a "check-box" Lp(a) order to the preoperative TAVR order set were instituted. Retrospective chart review was performed in 229 patients requiring TAVR between May 2013 and September 2018. Of these patients, 57% had an Lp(a) level measured; testing rates increased from 0% in 2013 to 96% in 2018. Lipoprotein(a) testing occurred in 11% of patients before and in 80% of patients after the "check-box" order set ( P < .001). The prevalence of elevated Lp(a) (≥30 mg/dL) was 35%; these patients had a higher incidence of coronary artery disease requiring revascularization compared with patients with normal Lp(a) (65% vs 47%; P = .047). Patients with Lp(a) ≥30 mg/dL also had higher incidence of paravalvular leak compared with those with normal Lp(a) (13% vs 4%; P = .04). This study defines the prevalence of elevated Lp(a) in advanced stages of CAVS and provides a practice pathway to assess procedural complications and long-term outcomes of TAVR in patients with elevated Lp(a) levels.

Lack of Correlation of Carotid Intima-Media Index and Peripheral Artery Disease.

INTRODUCTION: Increased carotid intima-media thickness (IMT) measurement is usually seen as a surrogate marker of peripheral artery disease (PAD) but there is scarce cumulated evidence to support this view. AIM: To evaluate prevalence of increased IMT among patients with symptomatic PAD as well as the frequency of some cardiovascular risk factors in these patients. METHODS: They were recruited 230 patients with diagnosis of medium peripheral artery disease in the Vascular Surgery Service outpatient's office. Serum cystatin C, homocysteine, and lipoprotein (a) were measured. GFR was estimated using the CKD-EPI equation and the Larsson one from cystatin C. RESULTS: The global prevalence of increased IMT was 16.5% (n = 38, 95% CI 12.3-21.9). In all the frequency of hyperlipoproteinemia (a) was 34.2% (95% CI 28.4-40.5%). The global prevalence of hyperhomocysteinemia was 61.5% (95% CI 54.6-68.1%) and the proportion of patients with high cystatin C levels was 38.5% (95% CI 32.1-42.5). The prevalence of stage III chronic kidney disease or higher by CKD-EPI formula was much lesser (13.6%, 95% CI 9.7-18.7) as was the frequency obtained by the Larsson equation (28.7%, 95% CI 23.2-34.9). No differences were found between groups. CONCLUSIONS: Increased IMT is not common among PAD patients. Hyperlipoproteinemia (a) and hyperhomocysteinemia are very frequent in these patients. High serum cystatin levels are also very prevalent but reduced GFR is not so frequent. There were no differences in the prevalence of the studied cardiovascular risk factors between those patients with increased IMT and those ones with normal IMT.

High levels of lipoprotein (a) and premature acute coronary syndrome.

BACKGROUND AND AIMS: High levels of lipoprotein(a) [Lp(a)] are associated with increased risk of acute coronary syndrome (ACS). We explored whether Lp(a) exhibits a stronger association with premature ACS. METHODS: A case-control study was conducted; 1457 patients with a history of ACS (54.8 ± 13 years, 86% males) and 2090 age-sex matched adults free of cardiovascular disease were enrolled. Bio-clinical characteristics [risk factors, low-density lipoprotein-cholesterol, Lp(a)] were derived through standard procedures. RESULTS: A 10 mg/dL increase in Lp(a) was associated with 4% (95% CI, 1.01 to 1.02) higher likelihood of having ACS in younger (<45 years) and 2% (95% CI, 1.01 to 1.02) higher likelihood in middle-aged (45-60 years) individuals. Adjusting for common risk factors, elevated Lp(a), i.e. >50 mg/dL, was still associated with increased likelihood of ACS in younger adults (<45 years) (OR = 2.88, 95% CI, 1.7 to 4.6) and in middle aged ones (45 and 60 years) (OR = 2.06, 95% CI, 1.4 to 3.2), but not in older participants (>60 years) (OR = 1.31, 95% CI, 0.8 to 2.4). CONCLUSIONS: Lp(a) seems to be an independent risk factor for ACS in individuals <45 years, and high Lp(a) levels increase by ∼3folds the risk for ACS. The association is preserved but is less in middle-aged individuals (45-60 years) and is abolished >60 years.

Effect of different lipid apheresis methods on plasma polyunsaturated fatty acids.

Lipoprotein apheresis has been shown to improve the cardiovascular outcome in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). An elevated intake of omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with a reduced cardiovascular risk. However, until now only little is known about the effect of apheresis treatment on the levels of omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA) in patients. Using gas chromatography (GC) the present study analyzed the content of n-6 and n-3 PUFA as well as saturated fatty acids and monounsaturated fatty acids in the plasma of 20 patients with hyperlipidemia undergoing regular lipoprotein apheresis procedures in direct pre- and post-therapy measurements. Lipoprotein apheresis uniformly reduced the concentrations of arachidonic acid (AA), EPA and DHA fatty acids analyzed in the plasma. However, the three different apheresis methods analyzed (heparin precipitation, membrane filtration and direct absorption) had different effects on the fatty acid profile in the plasma. We found that heparin precipitation and direct absorption apheresis procedures led to a significant decrease of plasma n-3 and n-6 PUFA by 40-50%. In contrast, patients undergoing membrane filtration apheresis, levels pre- and post-apheresis did not change significantly, with AA and EPA being only reduced by approximately 10% while levels of DHA were maintained pre- and post-apheresis. In contrast, total triglyceride levels were lowered most potently by membrane filtration apheresis. In summary, heparin precipitation and direct absorption apheresis approaches significantly lowered polyunsaturated fatty acids in plasma, while membrane filtration did not. This might have implications for cardiovascular and inflammatory risk/benefit profiles associated with n-6 and n-3 PUFA levels in the body.

Lipoprotein apheresis downregulates IL-1α, IL-6 and TNF-α mRNA expression in severe dyslipidaemia.

BACKGROUND AND AIMS: Dyslipidaemias are associated with cardiovascular mortality and morbidity, driven by unstable atherosclerotic plaques with inflammatory infiltrates. Levels of messenger RNA (mRNA) for pro-inflammatory cytokines have been positively correlated with atherosclerotic disease progression. Therapeutic lipoprotein apheresis (LA) reduces plasma lipid levels and reduces inflammation. We evaluated the effects of LA on expression of mRNA coding for key pro-inflammatory cytokines in patients with dyslipidaemia, homo-/hetero-zygous familial hypercholesterolaemia (HoFH, HeFH) or hyperlipoprotein(a)aemia [hyperLp(a)] and associated coronary artery disease (CAD). APPROACH: Ten patients (five males and five females, mean age 47 ± 9.2 years) were enrolled, all with HyperLp(a) or confirmed genetic diagnoses of dyslipidaemia, HoFH, or HeFH; all had associated CAD. mRNA determinations were via reverse transcriptase polymer chain reaction (RT-qPCR). RESULTS: LA was associated with downregulation of mRNA expression for IL-1α, IL-6 and TNF-α, starting after the first LA session. The observed reduction was progressively enhanced during the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session (IL-1α: -49%, p < 0.001; IL-6: -35%, p < 0.001; TNF-α: -56%, p < 0.001). CONCLUSIONS: LA suppresses the expression of IL-1α, IL-6 and TNF-α mRNA in patients with dyslipidaemias. This may contribute to the arterial anti-inflammatory effect of LA.

Kinetics of Lipoprotein(a) in patients undergoing weekly lipoprotein apheresis for Lp(a) hyperlipoproteinemia.

INTRODUCTION: Lipoprotein apheresis (LA) represents the only effective therapeutic option for patients with elevated Lipoprotein(a) (Lp(a)) levels. We aimed at analyzing the Lp(a) reduction, rebound rates as well as mean interval values between two weekly apheresis sessions, since this might be important for the prediction of the residual cardiovascular risk and development of individualized approaches for this special therapeutic strategy. MATERIALS AND METHODS: 20 patients under weekly and 2 patients under twice weekly apheresis were included. We measured serum concentrations of Lp(a), total, LDL-, HDL - cholesterol and triglycerides daily over 7 days after single LA sessions. RESULTS: Mean Lp(a) levels was 158.1 ± 69.82 nmol/l before the LA session, decreased acutely by 76 ± 7% and increased to 97 ± 13% of the baseline value within 7 days in patients under weekly treatment. By mathematical modeling, the acute Lp(a) reduction can be calculated from the function: y (nmol/l) = 3.415 + 0.738 * x (R2 = 0.970), where x is the baseline Lp(a) value. The recovery rate can be predicted from the equation: y (%) = 22.49 + 18.64 * x - 1.14 * x2 (R2 = 0.874), where x is the day after apheresis. The empirical formula for the mean interval value is: y (nmol/l) = x - 12, where x is the absolute reduction in nmol/l. CONCLUSION: We modeled - for the first time - equations to predict the course of Lp(a) serum levels under weekly LA which are simple, reliable and enable the development of optimal individualized protocols of this costly lipid lowering therapy.

Most significant reduction of cardiovascular events in patients undergoing lipoproteinapheresis due to raised Lp(a) levels - A multicenter observational study.

OBJECTIVES: Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study. METHODS: 113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start. RESULTS: Before start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (-77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (-74%, p < 0.001) than in subjects with isolated hypercholesterolemia (-53%, p 0.06). CONCLUSION: This study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted.

Persistent High Non-High-Density Lipoprotein Cholesterol in Early Childhood: A Latent Class Growth Model Analysis.

OBJECTIVES: To examine patterns of non-high-density lipoprotein (HDL) cholesterol in early childhood and identify factors associated with persistent high non-HDL cholesterol in healthy urban children. STUDY DESIGN: We identified all children enrolled in a primary care practice-based research network called TARGet Kids! (The Applied Research Group for Kids) with ≥3 laboratory measurements of non-HDL cholesterol. Latent class growth model analysis was performed to identify distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then categorized into "normal" vs "persistent-high" non-HDL cholesterol based on guideline cut-off values and logistic regression was completed to examine the association between trajectory group and the presence of anthropometric and cardiometabolic risk factors. RESULTS: A total of 608 children met inclusion criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9 months). Four trajectory groups were identified with 2 groups (n = 451) categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI 1.27-3.28) was associated significantly with persistent high non-HDL cholesterol, whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78), longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent high non-HDL cholesterol. CONCLUSIONS: Patterns of non-HDL cholesterol are identified during early childhood, and family history of high cholesterol was associated most strongly with persistent high non-HDL cholesterol. Future research should inform the development of a clinical prediction tool for lipids in early childhood to identify children who may benefit from interventions to promote cardiovascular health.

Lipoprotein(a) in nephrological patients.

In contrast to existing EAS/ESC guidelines on the management of lipid disorders, current recommendations from nephrological societies are very conservative and restrictive with respect to any escalation of lipid lowering/statin therapy. Furthermore, lipoprotein(a) (Lp(a)) - an established cardiovascular risk factor - has not even been mentioned. While a number of retrospective and prospective studies suggested that Lp(a) has relevant predictive value and might have - at least in stage-3 chronic kidney disease (CKD) - the same negative effects if draged along in non-CKD patients, there is no guidance on diagnostic or therapeutic procedures. The persistent lack of recognition automatically leads to therapeutic nihilism, which might pose a number of relatively young patients to a significantly increased risk for adverse cardiovascular events. Further evaluation of Lp(a) in CKD is very important to provide appropriate treatment to patients with high Lp(a) levels, even in the presence of CKD.

Lipoprotein(a)-hyperlipoproteinemia as cause of chronic spinal cord ischemia resulting in progressive myelopathy - successful treatment with lipoprotein apheresis.

High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life.Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.