Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial.

BACKGROUND AND AIMS: Lerodalcibep, a novel small recombinant fusion protein of a proprotein convertase subtilisin/kexin type 9 gene-binding domain (adnectin) and human serum albumin, demonstrated highly effective low-density lipoprotein cholesterol (LDL-C) reduction with monthly 300 mg in 1.2 mL subcutaneous dosing in Phase 2. In this global Phase 3 trial, the safety and efficacy of lerodalcibep were evaluated in heterozygous familial hypercholesterolaemia patients requiring additional LDL-C lowering. METHODS: Patients were randomized 2:1 to monthly subcutaneous injections of either lerodalcibep 300 mg or placebo for 24 weeks. The primary efficacy endpoints were the per cent change from baseline in LDL-C at Week 24 and the mean of Weeks 22 and 24. RESULTS: In 478 randomized subjects [mean age (range); 53 (18-80) years, 51.7% female, mean (SD) baseline LDL-C 3.88 (1.66) mmol/L], lerodalcibep reduced LDL-C, compared with placebo by an absolute amount of 2.08 (0.11) mmol/L [LS mean (SE); 95% confidence interval -2.30 to -1.87] with a percentage difference of -58.61 (3.25)% at Week 24 and by 2.28 (0.10) mmol/L (95% confidence interval -2.47 to -2.09) with a percentage difference of -65.0 (2.87)% at the mean of Weeks 22 and 24 (P < .0001 for all). With lerodalcibep, 68% of subjects achieved both a reduction in LDL-C ≥ 50% and the recommended European Society of Cardiology LDL-C targets during the study. Except for mild injection site reactions, treatment-emergent adverse events were similar between lerodalcibep and placebo. CONCLUSIONS: Lerodalcibep, a novel anti-proprotein convertase subtilisin/kexin type 9 gene small binding protein dosed monthly as an alternative to monoclonal antibodies, significantly reduced LDL-C in subjects with heterozygous familial hypercholesterolaemia with a safety profile similar to placebo.

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.

2023 Update on European Atherosclerosis Society Consensus Statement on Homozygous Familial Hypercholesterolaemia: new treatments and clinical guidance.

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy-both pharmacologic intervention and lipoprotein apheresis (LA)-is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Evaluation of the Effectiveness of Individually Tailored Lifestyle Intervention in Patients With Familial Hypercholesterolemia.

OBJECTIVES: The aim of this study was to evaluate the effect of a theoretically-based individually tailored lifestyle intervention on healthy lifestyle changes and improvement in disease management in patients with familial hypercholesterolemia (FH). METHODS: In this randomized controlled clinical trial, 120 patients with FH were randomly assigned (1:1) to receive education and counseling based upon the Transtheoretical Model of Health Behavioral Change (n = 60) or conventional clinical education (n = 60). All patients were evaluated for healthy lifestyle changes, adherence to therapy, lipid levels, blood pressure, body mass index, and waist measurement at baseline and at 12th and 24th weeks' visits. RESULTS: Motivational interviews resulted in a significant improvement in healthy lifestyle changes and treatment adherence in the intervention group. In addition, there were significant decreases in body mass index (-7.49%), low-density lipoprotein cholesterol (-37.14%), and blood pressure (13.3%) in the intervention group. CONCLUSIONS: Our results showed that an individually tailored lifestyle intervention was effective in facilitating healthy lifestyle changes and improvement in treatment adherence and in decreasing cardiovascular risk factors including cholesterol levels in patients with FH.

Management of LDL-cholesterol levels in patients with Diabetes Mellitus in Cardiology Practice: Real-life evidence of Under-treatment from the EPHESUS registry.

BACKGROUND AND AIMS: Effective treatment of high low-density lipoprotein cholesterol (LDL-C) levels has been shown to improve cardiovascular outcomes of patients with diabetes mellitus (DM). Herein, we aimed to provide insight to the real-life management of patients with DM in terms of LDL-C goal attainment and adherence to lipid management recommendations. Our objective was also to reveal the reasons of poor LDL-C goal attainment by assessing the perceptions of both physicians and patients. METHODS: We compared the diabetic and non-diabetic patients from the database of a nationwide registry conducted in cardiology outpatient clinics with regard to the demographic characteristics, educational status, comorbidities, medications, laboratory parameters and LDL-C goal attainment. Also, both the patients and attending physicians were surveyed to analyse perceptions and awareness of hypercholesterolemia. RESULTS: Of the 1868 consecutively enrolled patients, 873 (47%) had DM. Proportion of patients on statins was significantly lower in patients with DM (67.8% vs 55.3%; P < .001). The proportion of patients who attained LDL-C targets were lower among the diabetic patients (17.8% vs 15%; P = .06). The most common causes of the discontinuation of statin therapy were negative media coverage about statins (32.1%), and recommendations of physicians to stop the lipid lowering therapy (29.6%). Analysis of the physician survey revealed that the physicians could determine the off-target patients accurately (negative predictive value 98.4%) while the positive predictive value (48.8%) was low. The reasons for not attaining the LDL-C goals in diabetic patients were not prescription of statins (38%) and inadequate (eg low-dose, non-adherent) statin (28.3%) dosages. CONCLUSIONS: In real-life clinical cardiology practice, diabetic patients are far below the recommended LDL-C treatment goals. High-intensity statin treatment in diabetic population is still avoided because of the concerns about polypharmacy and drug interactions. Also, the inertia of physicians and even cardiologists is probably a major cause of refraining of prescription of optimal statin dosages.

LDL Apheresis and Lp (a) Apheresis: A Clinician's Perspective.

PURPOSE OF REVIEW: Lipoprotein apheresis is the most effective means of lipid-lowering therapy. However, it's a semi-invasive, time consuming, and chronic therapy with variable adherence. There are still no specific guideline recommendations for the management of patients on lipid apheresis. The purpose of this review is to discuss the clinical indications and major drawbacks of lipid apheresis in the light of recent evidence. RECENT FINDINGS: Lipoprotein apheresis should be initiated at early ages and performed frequently to receive the expected cardiovascular benefits. However, in clinical practice, most patients experience ineffective apheresis and fail to reach lipid targets. This real-world failure is due to several factors including late diagnosis, delayed referral, and improper frequency of procedures. All these denote that awareness is still low among physicians. Another important factor is the semi-invasive, time consuming nature of the apheresis, leading to high refusal and low adherence rates. Moreover, apheresis decreases quality of life and increases the risk of depression. Mental status is also deteriorated in patients with familial hypercholesterolemia on lipid apheresis. New effective lipid lowering agents are underway with promising cardiovascular results. To overcome the drawbacks, a structured approach, including standardized protocols for lipoprotein apheresis with regular cardiovascular follow-up is warranted. New effective lipid lowering agents with documented cardiovascular benefit, should be integrated into the treatment algorithms of patients on lipoprotein apheresis.

Familial Hypercholesterolemia: Global Burden and Approaches.

PURPOSE OF REVIEW: Familial hypercholesterolemia (FH) is the most common genetic metabolic disorder characterized by markedly elevated LDL-C levels from birth leading to atherosclerotic cardiovascular disease (ASCVD) and premature deaths. The purpose of this review is to share the current knowledge in the diagnosis, risk estimation, and management of patients with FH in the light of recent evidence and guideline recommendations. RECENT FINDINGS: Recent registries underscored the prevalence of FH as 1/200-250 translating to an almost 1500 million subjects suffering from FH worldwide. However, only a minority of FH patients are identified early and effectively treated. In most cases, mutations in the LDL-receptor (LDLR) gene and to a lesser degree in the apolipoprotein B-100 (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL-receptor adaptor protein 1 (LDLRAP1) genes cause FH. Diagnostic scores such as Dutch Lipid Clinic Network criteria using clinical manifestations are helpful in identifying FH. Traditional risk factors and high lipoprotein(a) affect the course of the disease. Vascular ultrasound imaging and coronary calcium scoring are helpful for further risk estimation of these patients. Getting to LDL-C goals is possible with currently available treatments including statins, ezetimibe, and PCSK9 inhibitors, as well as lipoprotein apheresis, lomitapide, and mipomersen in more severe phenotypes. Additionally, novel agents bempedoic acid, inclisiran, and evinacumab expanded the treatment choices for some patients with FH. Early diagnosis and initiation of LDL-C lowering are still required to achieve the greatest reduction in ASCVD morbidity and mortality in patients with FH. FH is a common genetic disorder characterized by markedly elevated LDL-C levels from birth onward, resulting in significantly increased risk for ASCVD. Despite major advances in our understanding of the disease and effective therapies, FH is still underdiagnosed and undertreated. Early initiation of LDL-C lowering by increased awareness of FH among the healthcare professionals, patients, and the public is necessary to achieve meaningful reduction in ASCVD morbidity and mortality in these patients.

Brief recommendations on the management of adult patients with familial hypercholesterolemia during the COVID-19 pandemic.

Individuals with Familial Hypercholesterolaemia (FH) are at very high risk of cardiovascular disease, which is associated with poor outcomes from coronavirus infections. COVID-19 puts strain on healthcare systems and may impair access to routine FH services. On behalf of the International Lipid Expert Panel (ILEP) and the European FH Patient Network (FH Europe), we present brief recommendations on the management of adult patients with FH during the COVID-19 pandemic. We discuss the implications of COVID-19 infections for FH patients, the importance of continuing lipid-lowering therapy where possible, issues relating to safety monitoring and service delivery. We summarise the evidence for additional benefits of statins and other lipid-lowering drugs during viral infections. The recommendations do not override in any way the individual responsibility of physicians to make appropriate and accurate decisions taking into account the condition of a given patient and the doses, rules, and regulations applicable to drugs and devices at the time of their prescription/use.

The reasons of poor lipid target attainment for secondary prevention in real life practice: Results from EPHESUS.

OBJECTIVE: There are lack of studies considering the suboptimal management of dyslipidemia especially in cardiology outpatient clinics. This study was conducted to assess the patient adherence to cholesterol treatment recommendations and attainment of low-density-lipoprotein cholesterol (LDL-C) goals. METHODS: EPHESUS (NCT02608645) is a national, observational and multicenter registry which has been designed as a cross-sectional study to allow inclusion of all consecutive patients with hypercholesterolemia in cardiology outpatient clinics. The present subgroup analyses of the EPHESUS trial included patients with known peripheral artery disease or atherosclerotic cerebrovascular disease, and coronary heart disease namely secondary prevention. RESULTS: The present analysis of the EPHESUS study included 1482 patients (62.79 ± 10.4 years, 38.2% female) with secondary prevention from 40 sites in Turkey. Regarding recommended lipid targets for LDL-C, only 267 patients (18%) were below the target of 70 mg/dL. Females were significantly more off-target when compared with male patients (396, 85.5% vs 67, 14.5%; P = 0.017). Moreover, the achievement of LDL-C goal was significantly decreased with illiteracy (233, 19.2% vs 35, 13.1%; P = 0.02). Patients who think that the cholesterol treatment should be terminated when the cholesterol level of a patient has normalised were higher in the off-target group (34.0% vs 24.7%, P < 0.001). Besides, physician perceptions about LDL-C goal for secondary prevention were significantly related with LDL-C target attainment. CONCLUSIONS: EPHESUS is an important study with large population in terms of representing real-life practice of the adherence to dyslipidemia guidelines in secondary prevention patients in Turkey. Perceptions, knowledge, and compliance with the guidelines for secondary prevention have increased, but it is far below from the desired levels even in cardiology outpatient clinics. There is a need for patients' and physicians' education regarding the treatment of hyperlipidemia.

Right ventricular free-wall longitudinal speckle tracking strain in patients with pulmonary arterial hypertension under specific treatment.

BACKGROUND: Right ventricular (RV) dysfunction is a major determinant of outcomes in patients with pulmonary arterial hypertension (PAH), although the optimal measure of RV function is poorly defined. We evaluated the utility of RV free-wall speckle tracking strain as an assessment tool for RV function in patients with PAH who are already under specific treatment compared with conventional echocardiographic parameters and investigated the relationship of RV free-wall strain with clinical hemodynamic parameters of RV performance. METHODS: Right ventricular free-wall strain was evaluated in 92 patients (Group-1 and Group-4 pulmonary hypertension) who were on PAH-specific treatment for at least 3 months. Right atrial (RA) area, RV FAC, TAPSE, tricuspid S, functional class, 6-minute walking distance, and NT-proBNP were studied. The mean duration of follow-up was 222±133 days. RESULTS: All patients were under PAH-specific treatment, and mean RV free-wall strain was -13.16±6.3%. RV free-wall strain correlated well with functional class (r=.312, P=.01), NT-proBNP (r=.423, P=.0001), RA area (r=.427, P=.0001), FAC (r=-.637, P=.0001), TAPSE (r=-.524, P=.0001), tricuspid S (r=-.450, P=.0001), 6-minute walking distance (r=-.333, P=.002). RV free-wall strain significantly correlated with all follow-up adverse events, death, and clinical right heart failure (RHF) (P=.04, P=.03, P=.02, respectively). According to the receiver operator characteristic analysis, the cutoff value for RV free-wall strain for the development of clinical RHF was -12.5% (sensitivity: 71%, specificity: 67%) and for all cardiovascular adverse events (death included) was -12.5% (sensitivity: 54%, specificity: 64%). CONCLUSION: Assessment of RV free-wall strain is a feasible, easy-to-perform method and may be used as a predictor of RHF, clinical deterioration, and mortality in patients already under PAH-specific treatment.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Rationale and Design.

Familial hypercholesterolemia (FH) is a genetic disorder with well-known genetic transmission and clinical course. Despite great recent progress, FH is still underestimated, under-diagnosed and thus undertreated. Furthermore it represents a significant healthcare challenge as a common risk factor for the premature development of coronary heart disease. The ScreenPro FH Project is an international network project aiming at improving complex care - from timely screening, through diagnosis to up-to-date treatment of familial hypercholesterolemia in Central, Eastern and Southern Europe. An important task for the project is to harmonise and unify diagnostic and therapeutic approaches in participating countries, where the situation differs from country to country. Countries with more experience should serve as a model for countries developing the FH network.Key words: diagnosis - familial hypercholesterolemia - screening - treatment optimization.

ScreenPro FH - Screening Project for Familial Hypercholesterolemia in Central, Southern and Eastern Europe: Basic Epidemiology.

INTRODUCTION: Despite great recent progress, familial hypercholesterolemia (FH) is still underestimated, under-diagnosed and thus undertreated worldwide. We have very little information on exact prevalence of patients with FH in the Central, Eastern and Southern Europe (CESE) region. The aim of the study was to describe the epidemiological situation in the CESE region from data available. METHODS: All local leaders of the ScreenPro FH project were asked to provide local data on (a) expert guess of FH prevalence (b) the medical facilities focused on FH already in place (c) the diagnostic criteria used (d) the number of patients already evidenced in local database and (e) the availability of therapeutic options (especially plasma apheresis). RESULTS: With the guess prevalence of FH around 1 : 500, we estimate the overall population of 588 363 FH heterozygotes in the CESE region. Only 14 108 persons (2.4 %) were depicted in local databases; but the depiction rate varied between 0.1 % and 31.6 %. Only four out of 17 participating countries reported the the LDL apheresis availability. CONCLUSION: Our data point to the large population of heterozygous FH patients in the CESE region but low diagnostic rate. However structures through the ScreenPro FH project are being created and we can hope that the results will appear soon.Key words: diagnosis - epidemiology - familial hypercholesterolemia - screening.

Current practice in identifying and treating cardiovascular risk, with a focus on residual risk associated with atherogenic dyslipidaemia.

A panel of European experts on lipids and cardiovascular disease discussed clinical approaches to managing cardiovascular risk in clinical practice, including residual cardiovascular risk associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence, and its impact on cardiovascular risk. Atherogenic dyslipidaemia can be defined by high fasting triglyceride levels (≥2.3 mmol/L) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1.0 and ≤1.3 mmol/L in men and women, respectively) in statin-treated patients at high cardiovascular risk. The use of a single marker for the diagnosis and treatment of AD, such as non-HDL-c, was advocated. Interventions including lifestyle optimization and low-density lipoprotein (LDL)-lowering therapy with statins (±ezetimibe) are implemented by all experts. Treatment of residual AD can be performed with the addition of fenofibrate, since it can improve the complete lipoprotein profile and reduce the risk of cardiovascular events in patients with AD. Specific clinical scenarios in which fenofibrate may be prescribed are discussed, and include patients with very high triglycerides (≥5.6 mmol/L), patients who are intolerant or resistant to statins, and patients with AD and at high cardiovascular risk. The fenofibrate-statin combination was considered by the experts to benefit from a favourable benefit-risk profile. Cardiovascular experts adopt a multifaceted approach to the prevention of atherosclerotic cardiovascular disease, with lifestyle optimization, LDL-lowering therapy, and treatment of AD with fenofibrate routinely used to help reduce a patient's overall cardiovascular risk.

[Homozygous familial hypercholesterolemia]. / Ailevi hiperkolesterolemi tedavisinde yeni ajanlar: Lomitapide--Mipomersen.

Familial hypercholesterolemia (FH) is caused by genetic deficiency of LDL receptors leading to extremely high cholesterol levels and atherosclerosis at early ages. For the prevention of early atherosclerotic cardiovascular events, effective reduction of LDL-cholesterol is necessary from the early ages. However, particularly in homozygous patients, it's almost impossible to achieve target LDL-cholesterol levels with antilipid agents including statin agents, due to the severe LDL receptor dysfunction. LDL apheresis is an effective treatment modality in severe AH patients. However, the invasive, chronic time consuming nature of this treatment decreases the compliance of these patients. Moreover, atherosclerosis progress in 25% of the patients undergoing regular and effective apheresis even though since early ages. Clinical data also indicate that there is still an unmet medical need for new effective treatments for AH patients. This review will address new therapeutic strategies targeting Apolipoprotein (Apo) B including MTTP inhibitor Lomitapideand oligonucleotide Mipomersen. As both agents are targeted against ApoB, they are expected to be effective even in receptor negative homozygous AH patients.

[Long-term follow-up in patients with homozygous familial hypercholesterolemia; 13-year experience of a university hospital lipid clinic]. / Homozigot ailevi hiperkolesterolemili hastalarin uzun dönem izlemi:Bir u¨niversite hastanesi lipit polikliniginin 13 yillik deneyimi.

OBJECTIVES: Familiar hypercholesterolemia (FH) is a genetic disease characterized with extremely high levels of cholesterol leading to premature atherosclerosis. In homozygous individuals (HoFH) cardiovascular events could develop in childhood. In this article, long-term clinical experience with adult HoFH patients who are followed in Department of Cardiology, Ege University Faculty of Medicine is presented. STUDY DESIGN: Seventeen HoFH patients (11 females, 6 males) who are being followed between the years 2000-2013 were included. All data including clinical characteristics, family history, lipid levels, treatment, lipid-apheresis, cardiovascular events, complications were obtained retrospectively from patient chart records. RESULTS: Mean age was 31 ± 10 years at admission to our clinic. First diagnosis age was 25 ± 14. At diagnosis, mean cholesterol level was 625 ± 136 mg/dl. Admission complaints were dermatologic (41%) and ischemic symptoms (41%). A total of 3 patients (18%) were diagnosed during family screening. 65% of the patients' parents had consanguineous marriage. Xantomas was present in 59%, aortic valve pathology in 59%, and carotid artery plaques in 47%. Coronary artery disease was documented in 59%. Though all patients had indication for apheresis, 10 patients received apheresis due to high refusal rate. Age at the first apheresis was 27 ± 12 (minimum 10-maximum 42) and adherence to apheresis was 60%. With 2 years regular apheresis skin depositions were vanished, however carotid atherosclerosis and aortic pathology progressed. During the 43 ± 42 months follow-up, 4 patients died (mean age: 25 ± 5). CONCLUSION: Diagnosis is late in HoAH. Due to the delayed treatment of lipid apheresis, atherosclerosis and aortic stenosis progress in these patients. The awareness of the physicians and knowledge of the public is warranted.

Clinical practice recommendations on lipoprotein apheresis for children with homozygous familial hypercholesterolaemia: An expert consensus statement from ERKNet and ESPN.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation.

Effect of fluid management guided by bioimpedance spectroscopy on cardiovascular parameters in hemodialysis patients: a randomized controlled trial.

BACKGROUND: Fluid overload is the main determinant of hypertension and left ventricular hypertrophy in hemodialysis patients. However, assessment of fluid overload can be difficult in clinical practice. We investigated whether objective measurement of fluid overload with bioimpedance spectroscopy is helpful in optimizing fluid status. STUDY DESIGN: Prospective, randomized, and controlled study. SETTING & PARTICIPANTS: 156 hemodialysis patients from 2 centers were randomly assigned to 2 groups. INTERVENTION: Dry weight was assessed by routine clinical practice and fluid overload was assessed by bioimpedance spectroscopy in both groups. In the intervention group (n = 78), fluid overload information was provided to treating physicians and used to adjust fluid removal during dialysis. In the control group (n = 78), fluid overload information was not provided to treating physicians and fluid removal during dialysis was adjusted according to usual clinical practice. OUTCOMES: The primary outcome was regression of left ventricular mass index during a 1-year follow-up. Improvement in blood pressure and left atrial volume were the main secondary outcomes. Changes in arterial stiffness parameters were additional outcomes. MEASUREMENTS: Fluid overload was assessed twice monthly in the intervention group and every 3 months in the control group before the mid- or end-week hemodialysis session. Echocardiography, 48-hour ambulatory blood pressure measurement, and pulse wave analysis were performed at baseline and 12 months. RESULTS: Baseline fluid overload parameters in the intervention and control groups were 1.45 ± 1.11 (SD) and 1.44 ± 1.12 L, respectively (P = 0.7). Time-averaged fluid overload values significantly decreased in the intervention group (mean difference, -0.5 ± 0.8 L), but not in the control group (mean difference, 0.1 ± 1.2 L), and the mean difference between groups was -0.5 L (95% CI, -0.8 to -0.2; P = 0.001). Left ventricular mass index regressed from 131 ± 36 to 116 ± 29 g/m(2) (P < 0.001) in the intervention group, but not in the control group (121 ± 35 to 120 ± 30 g/m(2); P = 0.9); mean difference between groups was -10.2 g/m(2) (95% CI, -19.2 to -1.17 g/m(2); P = 0.04). In addition, values for left atrial volume index, blood pressure, and arterial stiffness parameters decreased in the intervention group, but not in the control group. LIMITATIONS: Ambulatory blood pressure data were not available for all patients. CONCLUSIONS: Assessment of fluid overload with bioimpedance spectroscopy provides better management of fluid status, leading to regression of left ventricular mass index, decrease in blood pressure, and improvement in arterial stiffness.

Pulmonary arterial hypertension and pregnancy.

This is the case report of a pregnant woman who refused pregnancy termination when diagnosed with pulmonary arterial hypertension (PAH) functional class 2-3 at the 24th week of gestation and of her newborn. A pregnant woman with PAH functional class 2-3 was treated with inhaled prostacyclin analog (iloprost), oral sildenafil, oxygen, and low molecular weight heparin. She delivered at 32nd week by Cesarean section. The infant required oxygen up to 36th week postconceptional age and had a short steroid treatment. The mother needed close cardiovascular monitorization, intensive oxygen and pulmonary vasodilator therapy for 2 months and was discharged with oxygen and oral iloprost treatment. A multidisciplinary approach together with pulmonary vasodilator therapy may be succesful in such a high-risk pregnant woman.

Dyslipidemia prevalence in nonobese, nondiabetic patients with obstructive sleep apnea: does sex matter?

STUDY OBJECTIVES: Dyslipidemia in obstructive sleep apnea (OSA) has been attributed to confounding obesity and/or diabetes. This study aimed to examine lipid profiles in nondiabetic, nonobese patients with OSA and identify the possible effects of age and sex. METHODS: We retrospectively evaluated the lipid parameters of 3,050 adults who underwent polysomnography. A total of 2,168 patients were excluded due to obesity (body mass index ≥ 30 kg/m2), diabetes, alcoholism, untreated hypothyroidism, lipid-lowering drug use, missing sleep data, or treatment for suspected OSA. RESULTS: Of 882 patients (75% males, aged 46.8 ± 12.2 years) included in the study, 88.4% had OSA. Levels of total cholesterol (P = .003), low-density-lipoprotein (LDL) cholesterol (P = .005), non-high-density-lipoprotein (non-HDL) cholesterol (P = .001), and triglycerides (P = .007) were significantly higher in patients with OSA than in those without, whereas HDL-cholesterol levels did not differ. The proportion of patients with hypercholesterolemia and/or elevated non-HDL cholesterol (> 160 mg/dL) was significantly higher in OSA than in non-OSA. Correlation analyses by sex revealed stronger and more significant relationships between lipid parameters and apnea-hypopnea index in women than in men (r = .135, P < .001, vs r = .080, P = .043 for total cholesterol; r = .111, P < .001, vs r = .080, P = .046 for non-HDL cholesterol; r = .122, P < .001, vs r = .061, P = .107 for LDL cholesterol, respectively). In regression analysis, the rate of hypercholesterolemia increased with age (P < .001 for women and P = .031 for men); non-HDL- and LDL-cholesterol levels significantly increased with OSA severity (P = .035 and P = .023, respectively) and age (P = .004 and P = .001, respectively) in women. CONCLUSIONS: After excluding confounding obesity and diabetes, patients with OSA have an impaired lipid profile including total cholesterol, LDL cholesterol, non-HDL cholesterol, and triglycerides. A significant association between dyslipidemia and OSA severity was observed in women but not in men. CITATION: Basoglu OK, Tasbakan MS, Kayikcioglu M. Dyslipidemia prevalence in nonobese, nondiabetic patients with obstructive sleep apnea: does sex matter? J Clin Sleep Med. 2023;19(5):889-898.