Lipoprotein Apheresis: Current Recommendations for Treating Familial Hypercholesterolemia and Elevated Lipoprotein(a).

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) and hyperlipoproteinemia(a) are relatively common disorders, posing a significant health burden due to increased risk of atherosclerotic cardiovascular disease (ASCVD). Development of electronic health record-based strategies with a linkage to the genetic test results has increased awareness, detection, and control of heritable lipid disorders. This review attempts to critically examine available data to provide a summary of the current evidence for lipoprotein apheresis in FH and elevated lipoprotein(a) (Lp(a)). REVIEW FINDINGS: Availability and indications for lipoprotein apheresis vary across the globe. On average, greater than 60% of atherogenic apoB-containing lipoproteins are immediately reduced following a single procedure, translating in substantial reduction of incident ASCVD events, and preventing accelerated vascular aging. Simultaneous lipid-lowering therapy targeting low-density lipoprotein (LDL) and Lp(a) enhances the efficacy of lipoprotein apheresis. Lipoprotein apheresis alters the proteomics of the lipoprotein particles, including reduction in the concentration of the oxidized-LDL and Lp(a) particles, and proinflammatory apoE bound to HDL particles and remnant lipoproteins. Other effects attributed to lipoprotein apheresis include improvement in blood rheology, endothelial function, microvascular flow, myocardial perfusion, reduction in circulating inflammatory markers. Development of lipoprotein apheresis registries provides data on benefits, challenges, and barriers to inform pertinent healthcare policies. Lipoprotein apheresis is a safe and effective procedure for lowering cholesterol in patients with combined and isolated FH and elevated Lp(a). It reduces the burden of ASCVD and improves long-term prognosis. A team approach is required by the patient, medical staff, and healthcare provider to initiate and maintain a lipoprotein apheresis program.

[Genetic diseases of lipid metabolism - Focus familial hypercholesterolemia]. / Genetische Erkrankungen des Lipidstoffwechsels.

Congenital disorders of lipid metabolism are characterised by LDL-C concentrations > 190 mg/dl (4.9 mM) and/or triglycerides > 200 mg/dl (2.3 mM) in young individuals after having excluded a secondary hyperlipoproteinemia. Further characteristics of this primary hyperlipoproteinemia are elevated lipid values or premature myocardial infarctions within families or xantelasms, arcus lipoides, xanthomas and abdominal pain. This overview summarises our current knowledge of etiology and pathogenesis of primary hyperlipoproteinemia.

Effect and significance of hyperlipoproteinemia on stent thrombosis in patients with implanted drug-eluting stents: The 5-year follow up study.

BACKGROUND: Elevated blood lipid level, also known as hyperlipoproteinemia (HLP), is the most common metabolic disorder in the general population. According to US National Heart Institute data, about 36% of adults and 10% of children aged 9 to 12 have elevated cholesterol levels. The risk of ischemic heart disease increases by 2-3% with every 1% increase in total cholesterol levels. Therefore, men aged 55-65 with a 10% increase in total cholesterol have about 38% increased ischemic heart disease mortality. The study's main objective is to determine the occurrence of thrombotic complications in patients in whom first-generation drug-eluting stents are implanted and how these events are influenced by the presence of HLP. METHODS: The study is retrospective, clinical, and non-interventional with a five-year follow-up period for each patient. Initially, 800 patients undergoing index percutaneous coronary angioplasty with sirolimus-eluting and paclitaxel-eluting stent implantation were enrolled. Clinical data collected included cardiac disorders, the presence of diabetes mellitus, hyperlipoproteinemia, and smoking as a risk factor. In the examined group of patients, stent thrombosis was monitored according to Academic Research Consortium (ARC) criteria. RESULTS: The study included 800 patients who underwent percutaneous coronary angioplasty index. At the end of the follow-up period, 701 patients (87.6%) completed the clinical trial and were included in the statistical analysis. Stent thrombosis, determined according to ARC criteria, was reported as 'definitive stent thrombosis' in 22 patients (3.06%), 'probable stent thrombosis' in 1 patient (0.14%), and 'possible stent thrombosis' in 1 patient (0.14%). Of the 404 patients with HLP, 120 patients had a total cholesterol value >300 mg/dL. Twenty patients with definitive stent thrombosis had cholesterol >300 mg/dL. Patients with probable and possible stent thrombosis did not have HLP. A comparison of patients with stent thrombosis, with HLP and without HLP, revealed a statistically significant difference (16.67% vs. 1.35%, p <0.001). Comparing patients with unstable angina pectoris, with cholesterol value >300 mg/dL and without HLP, a statistically significant difference was observed (71.7% vs. 17.2%, p <0.001). CONCLUSIONS: We report on the long-term follow up of patients with stent thrombosis after drug-eluting stent insertion with and without HLP. The results suggest that HLP influences the development of coronary disease, with a significant influence on complications following percutaneous coronary intervention.

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)

Biomarcadores cardiacos de aterotrombosis y su implicación en la estimación del riesgo de enfermedad cardiovascular / Cardiac biomarkers of atherothrombosis and their implication in estimating the risk of cardiovascular disease

Introducción: Las innovadoras estrategias para la estimación del riesgo cardiovascular que apelan al empleo de biomarcadores cardiacos de aterotrombosis, han evidenciado ser superiores en la estratificación del riesgo cardiovascular por encima de aquellas predicciones basadas exclusivamente en la evaluación de factores de riesgo tradicionales de manera aislada. Se realizó una revisión bibliográfica, análisis y categorización de diferentes artículos en las bases de datos Cumed, Lilacs, SciELO, Medline, los términos clave para la búsqueda fueron: homocisteína, lipoproteína (a) y riesgo cardiovascular, en español, inglés y portugués. Se consideraron artículos originales, de revisión, incluyendo revisiones sistemáticas y metaanálisis posteriores al año 2000. Objetivo: Analizar los biomarcadores cardiacos de aterotrombosis, involucrados en el desarrollo de la enfermedad cardiovascular aterosclerótica y sus complicaciones trombóticas. Desarrollo: La evidencia acumulada sustenta que biomarcadores cardiacos como la hiperhomocisteinemia, la hiperlipoproteinemia (a), el incremento de los niveles plasmáticos del fibrinógeno, el factor VII coagulante, el inhibidor del activador tisular del plasminógeno tipo 1 y la proteína C reactiva, son herramientas de gran utilidad para estratificar el riesgo cardiovascular en individuos de riesgo intermedio, o con riesgo inusual o de riesgo indefinido, esencialmente en el ámbito de la prevención primaria y secundaria de la enfermedad cardiovascular . Conclusiones: La identificación de biomarcadores emergentes de aterotrombosis predictivos adicionales, es trascendental para una prevención y terapéutica más eficaz de la enfermedad cardiovascular aterosclerótica(AU)

Introduction: Innovative cardiovascular risk estimation strategies that use cardiac biomarkers of atherothrombosis have been shown to be superior in cardiovascular risk stratification that those predictions based exclusively on the evaluation of traditional risk factors in isolation. A bibliographic review, analysis and categorization of different articles was performed in the databases Cumed, Lilacs, Scielo, Medline, the key terms for the search were: "homocysteine", "lipoprotein (a)" and "cardiovascular risk", in Spanish, English and Portuguese languages. Original review articles were considered, including systematic reviews and published meta-analyzes after 2000. Objective: To analyze some of the cardiac biomarkers of atherothrombosis that may be involved in the development of atherosclerotic cardiovascular disease and its thrombotic complications. Development: Accumulated evidence supports that cardiac biomarkers such as: hyperhomocysteinemia, hyperlipoproteinemia (a), increased plasma fibrinogen levels, coagulant factor VII, Plasminogen Tissue Activator Inhibitor type 1 and C-reactive protein are tools of Very useful for stratifying cardiovascular risk in those individuals with intermediate risk, or with unusual or undefined risk, essentially in the field of primary and secondary prevention of cardiovascular disease. Conclusions: The identification of additional predictive emergent atherothrombosis biomarkers is crucial for a more effective prevention and therapy of atherosclerotic cardiovascular disease(AU)

Lipoprotein(a) is robustly associated with aortic valve calcium.

OBJECTIVES: To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC. METHODS: We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC. RESULTS: The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (ß 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase). CONCLUSIONS: Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

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.

Cardiovascular events in patients with familial hypercholesterolemia and hyperlipoproteinaemia (a): Indications for lipoprotein apheresis in Poland.

BACKGROUND: Lipoprotein apheresis (LA) is a safe method of reducing atherogenic lipoproteins and improving cardiovascular (CV) outcomes. We aimed to assess the reductions in low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in patients undergoing regular LA therapy and to evaluate its influence on the incidence rate of adverse cardiac and vascular events (ACVE) and major adverse cardiac events (MACE). METHODS: A longitudinal study in Poland evaluated the prospective and retrospective observational data of 23 patients with hyperlipoproteinaemia (a) [hyper-Lp(a)] and familial hypercholesterolemia (FH), undergoing 1014 LA sessions between 2013 and 2020. Their pre- and post-apheresis LDL-C and Lp(a) levels were assessed to calculate the acute percent reductions. The time period used to evaluate annual rates of ACVE and MACE before and after initiation of LA was matched in each patient. RESULTS: The pre-apheresis LDL-C and Lp(a) concentrations were 155 (107-228) (mg/dL) (median and interquartile range) and 0.56 (0.14-1.37) (g/L), respectively. LA therapy resulted in a reduction of LDL-C to 50 (30-73.5) (mg/dL) and of Lp(a) to 0.13 (0.05-0.34) (g/L), representing a percent reduction of 70.0% and 72.7% for LDL-C and Lp(a), respectively. We found a significant reduction in the annual rate of ACVE (0.365[0.0-0.585] vs (0.0[0.0-0.265]; P = .047) and MACE (0.365[0.0-0.585] vs 0.0[0.0-0.265]; P = .031). CONCLUSIONS: The findings of our study indicate that LA treatment in patients with hyperlipoproteinaemia (a) and FH on maximally tolerated lipid lowering therapies leads to a substantial reduction in LDL-C and Lp(a) concentrations and lowers CV event rates in Polish patients.

Hyperlipoproteinemia (a) is associated with breast cancer in a Han Chinese population.

To investigate the relationship between serum lipoprotein (a) (LP(a)) levels and breast cancer as well as the clinicopathologic characteristics of breast cancer in a Han Chinese population.This study included 314 breast cancer patients, 51 patients with benign breast tumors, and 185 healthy control subjects. All study subjects were Han Chinese with similar socio-economic backgrounds, who were local residents of Zhoushan, Zhejiang, China or who had lived in Zhoushan for a long period of time. Serum concentrations of LP(a) were determined using a latex-enhanced immunoturbidimetric assay. Clinicopathological characteristics of patients were retrieved from medical records, which included the histopathological type, grade, stage, and molecular subtype of the disease, the expression of estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67, and the level of reproductive hormones. Correlations between 2 groups were evaluated using the Spearman correlation analysis. Associations among ≥3 groups were interpreted using the Kruskal-Wallis H test or the logistic regression test.Elevated serum LP(a) levels were detected in breast cancer patients compared with healthy control subjects, but no significant differences in LP(a) were detected between breast cancer and benign tumor or between benign tumor and healthy control. In breast cancer patients, serum LP(a) levels were inversely associated with HER2 expression, but they were not significantly correlated with any other clinicopathologic characteristics of breast cancer evaluated in this study.Elevated serum LP(a) levels were associated with breast cancer in a Han Chinese population.

The moderating role of underlying predictors of survival in patients with brain stroke: a statistical modeling.

Determining subclinical Brain stroke (BS) risk factors may allow for early and more operative BS prevention measures to find the main risk factors and moderating effects of survival in patients with BS. In this prospective study, a total of 332 patients were recruited from 2004 up to 2018. Cox's proportional hazard regressions were used to analyze the predictors of survival and the moderating effect by introducing the interaction effects. The survival probability 1-, 5- and 10-year death rates were 0.254, 0.053, and 0. 023, respectively. The most important risk factors for predicting BS were age category, sex, history of blood pressure, history of diabetes, history of hyperlipoproteinemia, oral contraceptive pill, hemorrhagic cerebrovascular accident. Interestingly, the age category and education level, smoking and using oral contraceptive pill moderates the relationship between the history of cerebrovascular accident, history of heart disease, and history of blood pressure with the hazard of BS, respectively. Instead of considerable advances in the treatment of the patient with BS, effective BS prevention remains the best means for dropping the BS load regarding the related factors found in this study.

GC × GC-MS analysis and hypolipidemic effects of polyphenol extracts from Shanxi-aged vinegar in rats under a high fat diet.

Oxidative stress, inflammation and gut microbiota disorders can be induced by long-term high-fat diets (HFD). In order to confirm that polyphenols can improve these symptoms, polyphenols from Shanxi-aged vinegar (SAVEP) were extracted, and the components were detected by Comprehensive two-dimensional gas chromatography mass spectrometry (GC × GC-MS). 41 polyphenols include 18 phenolic acids and 17 polyphenols, which have not been reported. The mechanism of SAVEP on oxidative stress and inflammatory stress induced by HFD in rats and its regulating effect on intestinal flora disorder were studied. The results showed that SAVEP could significantly improve the lipid, inflammatory stress and oxidative stress related indicators compared with the Model group ("Model" refers to the group that successfully constructed a hyperlipidemia model by feeding HFD without any drugs or SAVEP in subsequent experiments.). In addition, SAVEP decreased the Firmicutes/Bacteroidetes ratio compared with the Model group, and elevated the relative abundance of beneficial bacteria. Conclusively, SAVEP can alleviate the oxidative stress and inflammatory stress caused by HFD, improving intestinal microbial disorders. The Spearman's correlation analysis revealed that Desulfovibrio, Lactobacillus and Akkermansia were correlated negatively with all of the inflammatory indicators, whereas Ruminococcus was the opposite. These results suggest that SAVEP may be a novel strategy against oxidative stress and inflammation, restoring the normal microbial community ecology of the gut and the treatment of metabolic syndromes.

Factores de riesgo metabólico y enfermedad cardiovascular asociados a obesidad en una población laboralmente activa / Metabolic Risk Factors and Cardiovascular Disease Associated with Obesity in an Actively Working Population

Introducción: La obesidad se relaciona con múltiples consecuencias adversas para la salud, como hipertensión, diabetes, hiperlipoproteinemia, enfermedad cardiovascular y otras. La prevalencia de estas entidades se ha incrementado en Cuba en las últimas décadas, muy asociadas a la ganancia ponderal. Objetivo: Describir la relación de la obesidad con la enfermedad cardiovascular y los factores de riesgo metabólicos como hipertensión arterial, hiperlipoproteinemia y diabetes mellitus. Métodos: Se realizó un estudio descriptivo, de corte transversal, en 2902 pacientes que acudieron a chequeo médico en el Hospital Militar Central Dr. Carlos J. Finlay. Se recolectaron datos generales, antropométricos y factores de riesgo metabólico de enfermedad cardiovascular. Se realizó glucemia en ayunas, colesterol, triglicéridos, creatinina y prueba de tolerancia a la glucosa oral en casos indicados. Se calculó el filtrado glomerular. Los pacientes fueron clasificados en bajo peso, normo peso, sobrepeso y obeso, se identificó la relación entre el estado nutricional y los factores de riesgo metabólico y la enfermedad cardiovascular. Resultados: Se encontró 44,5 por ciento de sobrepeso, más frecuente entre los hombres (45,5 por ciento) y 29,2 por ciento de obesidad, más frecuente entre las mujeres (31,6 por ciento). El índice de masa corporal aumentó progresivamente con la edad. Los valores de glucemia, colesterol, triglicéridos, HbA1c y filtrado glomerular aumentaron con el estado nutricional, así como la frecuencia de diabetes, hipertensión, hiperlipoproteinemia y enfermedad cardiovascular. Conclusiones: La obesidad fue muy frecuente en este grupo de pacientes, en los cuales se relacionaron directamente los factores de riesgo metabólico hipertensión arterial, hiperlipoproteinemia, diabetes mellitus y enfermedad cardiovascular(AU)

Introduction: Obesity is associated with multiple adverse health consequences, such as hypertension, diabetes, hyperlipoproteinemia, cardiovascular disease, and others. The prevalence of these conditions has increased in Cuba in recent decades, closely associated with ponderal gain. Objective: To describe the relationship of obesity with cardiovascular disease and metabolic risk factors such as hypertension, hyperlipoproteinemia, and diabetes mellitus. Methods: A descriptive, cross-sectional study was carried out with 2902 patients who went for a medical check-up at Dr. Carlos J. Finlay Central Military Hospital. General, anthropometric and metabolic risk factors for cardiovascular disease were gathered. The tests of fasting blood glucose, cholesterol, triglycerides, creatinine and oral glucose tolerance were performed in indicated cases. Glomerular filtrate was calculated. Patients were classified as low weight, normal weight, overweight, and obese. The relationship between nutritional status and metabolic risk factors and cardiovascular disease was identified. Results: 44.5 percent were found in overweight, more frequent among men (45.5 percent). 29.2 percent were found in obesity, more frequent among women (31.6 percent). The body mass index increased progressively with age. Blood glucose, cholesterol, triglycerides, HbA1c, and glomerular filtration levels increased with nutritional status, as well as the frequency of diabetes, hypertension, hyperlipoproteinemia, and cardiovascular disease. Conclusions: Obesity was very frequent in this group of patients, in which the metabolic risk factors were directly associated with high blood pressure, hyperlipoproteinemia, diabetes mellitus, and cardiovascular disease(AU)

IDOL G51S Variant Is Associated With High Blood Cholesterol and Increases Low-Density Lipoprotein Receptor Degradation.

OBJECTIVE: A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride. CONCLUSIONS: Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.

Lipoprotein(a): An underrecognized genetic risk factor for malignant coronary artery disease in young Indians.

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD-a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians.

Patterns of serum lipids derangements and cardiovascular risk assessment in patients with primary biliary cholangitis.

INTRODUCTION AND OBJECTIVES: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC. PATIENTS: All patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. The 10-year cardiovascular risk was estimated by the Framingham risk score. RESULTS: Fifty four patients with PBC were included and compared to 106 controls. Differences in total cholesterol (263.8±123.9mg/dl vs. 199.6±40, p=0.0001), LDL-cholesterol (179.3±114.8 vs. 126.8±34.7, p=0.0001), HDL-cholesterol (62.4±36.2mg/dl vs. 47.3±12.3, p=0.0001) and triglycerides (149.1±59.1mg/dl vs. 126.4±55.4, p=0.001) were found. Hypercholesterolemia (>240mg/dl) was found in 52.4% of the patients with PBC vs. 11% in the control group, high LDL-cholesterol (160-189mg/dl) in 45.2% of the patients with PBC vs. 10% in controls and hyperalphalipoproteinemia (HDL-cholesterol >60mg/dl) in 45.2% of the patients with PBC vs. 16% in controls. The 10-year cardiovascular risk was 5.3%±5.9 in the patients with PBC and 4.1%±5.7 in the control group (p=0.723, IC 95%=0.637-1.104). Only one cardiovascular event (stroke) in a patient with PBC was registered in a mean follow up time of 57.9±36.5 months. CONCLUSIONS: Marked derangements in serum lipids and a high frequency of dyslipidemias are found in patients with PBC, however, these do not increase the risk of cardiovascular events.

Accelerated atherosclerosis, hyperlipoproteinemia and insulin resistance in long-term survivors of Hodgkin lymphoma during childhood and adolescence.

Long-term survivors of Hodgkin lymphoma during childhood or adolescence (HL survivors) are at high risk of developing treatment-related late cardiovascular sequelae. In our study we evaluated the presence of modifiable cardiovascular risk factors (hypertension, hyperlipoproteinemia, hyperinsulinemia, obesity), endothelial and inflammatory markers (E-selectin, PAI-1, hs-CRP) and atherosclerotic changes in the common carotid arteries. Assessment was performed in 80 young adult Hodgkin lymphoma long-term survivors at more than 10 years after the potentially cardiovascular toxic anticancer treatment (median age at evaluation 34.7 years; range 24.1-40.9 years). The HL survivors were compared with 83 age- and gender-matched healthy volunteers. The HL survivors showed unfavorable lipid profiles compared to those of healthy controls: triglycerides (p=0.01), total cholesterol (p=0.0004), low density lipoprotein cholesterol (p=0.005). In HL survivors, we found a higher prevalence of hypertension (p=0.004) and insulin resistance - HOMA-IR (p=0.0002). Ultrasonographic examination of both common carotid arteries revealed a higher prevalence of atherosclerotic plaques (p=0.0009) and higher carotid intima-media thickness (p<0.0001) in HL survivors. Markers of oxidative stress (advanced oxidation protein products, oxidized low-density lipoprotein), inflammation (hs-CRP) and endothelial dysfunction (E-selectin, PAI-1) were also higher in HL survivors (p<0.0001, p=0.0002, p=0.0031, p=0.0087, p=0.004, respectively). Adult survivors of Hodgkin lymphoma during childhood and adolescence need closer follow-up with screening of metabolic syndrome components, unfavorable lifestyle factors and early management of these risk factors.

[Clinical biochemistry methods in objectiva evalution of overeating foood of carnivores (meat)by a phylogenetically herbivorous homo sapiens (a patient).]

The abuse of food of carnivores (meat) by phylogeneticallyI herbivorous Homo sapiens (a patient) initiates atherosclerosis. Addressing biogenetic law of E. Haeckel that ontogeny recapitulates phylogeny (a universal anamnesis), we suggest a diagnostic technique that allows evaluation of the meat diet abuse by a herbivorous Homo sapiens. This technique is based on application of phylogenetic theory of general pathology to clinical practice. The degrees of objective evaluation of nonphysiological overeating of meat are: the first, an increase in the fast plasma content of oleic triglycerides palmitoyl-oleyl-palmitate (POP). The second, hyperglyceridemia + an increase in low density lipoprotein cholesterol (LDL-CL) content. The third, increased plasma content of apoС-III. The fourth, an increase in the concentration of apoВ-48. If electrophoregrams are analyzed and hyperlipoproteinemia (HLP) type is determined according to WHO classification, the first degree of meat overeating is not informative, the second, corresponds to type IV HLP; the third, to type IIb HLP, and the forth, to type V HLP, i.e, the patient diet consists practically of the food of carnivores. Hyperlipoproteinemia coincides with insulin resistance syndrome, hyperglycemia and hyperinsulinemia, which is based on blood increase of fatty acids in the form of polar unesterified fatty acids (UFA). According to phylogenetic theory of general pathology, in vivo cells do not internalize glucose if there is a possibility to internalize UFA. Preventive examination allows evaluation of disorders in the biological function of trophology (food consumption). Thus, the use of different methods in the analysis of this function offers evaluation of the effectiveness of diet therapy from the level of disorders when treatment was started.

Hyperlipoproteinaemia(a) in patients with spondyloarthritis: results of the Cardiovascular in Rheumatology (CARMA) project.

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.

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.