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Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5–10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature

Mental status and physical activity in patients with homozygous familial hypercholesterolemia: A subgroup analysis of a nationwide survey (A-HIT1 registry)

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening disease due to high serum low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol-lowering interventions are fundamental for patients with HoFH

Parameters of Patients with Diabetes Mellitus (TEMD Obesity Study)

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro-and microvascular complications of patients are not apparent. Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes. Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy. Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes. Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity. (c) 2019 The Author(s) Published by S. Karger AG, BaselC1 [Sonmez, Alper; Haymana, Cem; Demirci, Ibrahim] Univ Hlth Sci, Gulhane Sch Med, Dept Endocrinol & Metab, TR-06018 Ankara, Turkey.[Yumuk, Volkan] Istanbul Univ, Cerrahpasa Med Fac, Dept Endocrinol & Metab, Istanbul, Turkey.[Barcin, Cem] Univ Hlth Sci, Gulhane Sch Med, Dept Cardiol, Ankara, Turkey.[Kiyici, Sinem] Univ Hlth Sci, Bursa Yuksek Ihtisas Training & Res Hosp, Dept Endocrinol & Metab, Bursa, Turkey.[Guldiken, Sibel] Trakya Univ, Med Fac, Dept Endocrinol & Metab, Edirne, Turkey.[Oruk, Gonca] Izmir Katip Celebi Univ, Ataturk Educ & Res Hosp, Dept Endocrinol & Metab, Izmir, Turkey.[Saydam, Basak Ozgen] Dokuz Eylul Univ, Med Fac, Dept Endocrinol & Metab, Izmir, Turkey.[Baldane, Suleyman] Selcuk Univ, Med Fac, Dept Endocrinol & Metab, Konya, Turkey.[Kutluturk, Faruk] Gaziosmanpasa Univ, Med Fac, Dept Endocrinol & Metab, Tokat, Turkey.[Kucukler, Ferit Kerim] Hitit Univ, Med Fac, Dept Endocrinol & Metab, Corum, Turkey.[Deyneli, Oguzhan] Marmara Univ, Med Fac, Dept Endocrinol & Metab, Istanbul, Turkey.[Cetinarslan, Berrin] Kocaeli Univ, Med Fac, Dept Endocrinol & Metab, Kocaeli, Turkey.[Sabuncu, Tevfik] Harran Univ, Med Fac, Dept Endocrinol & Metab, Urfa, Turkey.[Bayram, Fahri] Erciyes Univ, Med Fac, Dept Endocrinol & Metab, Kayseri, Turkey.[Satman, Ilhan] Istanbul Univ, Med Fac, Dept Endocrinol & Metab, Istanbul, Turkey.[Ayturk, Semra] Trakya Univ, Sch Med, Dept Endocrinol & Metab, Edirne, Turkey.[Yilmaz, Murat] Corlu REYAP Private Hosp, Dept Endocrinol & Metab, Corlu, Turkey.[Asik, Mehmet] Canakkale 18 March Univ, Sch Med, Dept Endocrinol & Metab, Canakkale, Turkey.[Dinccag, Nevin; Cakmak, Ramazan; Turker, Fulya; Idiz, Cemile; Hacisahinogullari, Hulya; Bagdemir, Elif; Yildiz, Busra; Haliloglu, Ozlem] Istanbul Univ, Sch Med, Dept Endocrinol & Metab, Cerrahpasa, Turkey.[Sancak, Seda] Univ Hlth Sci, Sch Med, Fatih Sultan Mehmet Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.[Ozsari, Levent; Cagiltay, Eylem] Univ Hlth Sci, Sch Med, Sultanabdulhamit Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.[Imre, Eren] Marmara Univ, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Sait Gonen; Boysan, S. Nur] Istanbul Sci Univ, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Altuntas, Yuksel; Ozturk, Feyza Yener] Univ Hlth Sci, Sch Med, Sisli Hamidiye Etfal Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.[Mert, Meral; Piskinpasa, Hamide] Univ Hlth Sci, Istanbul Bakirkoy Dr Sadi Konuk Training & Res Ho, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Aydin, Hasan] Yeditepe Univ, Sch Med, Dept Endocrinol & Metab, Istanbul, Turkey.[Ersoy, Canan; Oz Gul, Ozen] Uludag Univ, Sch Med, Dept Endocrinol & Metab, Bursa, Turkey.[Selek, Alev] Kocaeli Univ, Sch Med, Dept Endocrinol & Metab, Kocaeli, Turkey.[Dogru, Teoman; Kirik, Ali] Balikesir Univ, Sch Med, Dept Internal Med, Balikesir, Turkey.[Kebapci, Nur; Efe, Belgin] Eskisehir Osmangazi Univ, Sch Med, Dept Endocrinol & Metab, Odunpazari Eskisehir, Turkey.[Kaya, Ahmet; Cordan, Ilker] Necmettin Erbakan Univ, Sch Med, Dept Endocrinol & Metab, Konya, Turkey.[Kirac, Cem Onur] Selcuk Univ, Sch Med, Dept Endocrinol & Metab, Konya, Turkey.[Capa, Zehra] Univ Hlth Sci, Gulhane Sch Med, Ankara, Turkey.[Capa, Zehra] Gulhane Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Cesur, Mustafa] Private Guven Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Yetkin, Ilhan] Gazi Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Corapcioglu, Demet; Canlar, Sule] Ankara Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Yildiz, Okan Bulent; Sendur, Suleyman Nahit] Hacettepe Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Cakir, Bekir; Ozdemir, Didem] Yildirim Beyazit Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Corakci, Ahmet] Ufuk Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Kutlu, Mustafa] Private Bayindir Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Bascil Tutuncu, Neslihan; Bozkus, Yusuf] Baskent Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Cakal, Erman] Univ Hlth Sci, Sch Med, Diskapi Yildirim Beyazit Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Demirbas, Berrin] TOBB Univ, Sch Med, Dept Endocrinol & Metab, Ankara, Turkey.[Ertek, Sibel] Private Mem Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Altay, Mustafa; Dagdeviren, Murat] Univ Hlth Sci, Sch Med, Kecioren Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Abedi, Amir Hassein] Erciyes Univ, Sch Med, Dept Endocrinol & Metab, Kayseri, Turkey.[Cetinkalp, Sevki; Ozisik, Hatice] Ege Univ, Sch Med, Dept Endocrinol & Metab, Izmir, Turkey.[Yener, Serkan] Dokuz Eylul Univ, Sch Med, Dept Endocrinol & Metab, Izmir, Turkey.[Guney, Engin; Unubol, Mustafa] Adnan Menderes Univ, Sch Med, Dept Endocrinol & Metab, Aydin, Turkey.[Yaylali, Guzin Fidan; Topsakal, Senay] Pamukkale Univ, Sch Med, Dept Endocrinol & Metab, Denizli, Turkey.[Hekimsoy, Zeliha] Celal Bayar Univ, Sch Med, Dept Endocrinol & Metab, Manisa, Turkey.[Akbaba, Gulhan] Mugla Univ, Sch Med, Dept Endocrinol & Metab, Mugla, Turkey.[Aslan, Ibrahim] Univ Hlth Sci, Antalya Training & Res Hosp, Sch Med, Dept Endocrinol & Metab, Antalya, Turkey.[Balci, Mustafa Kemal; Dalkiran, Sefika] Akdeniz Univ, Sch Med, Dept Endocrinol & Metab, Antalya, Turkey.[Akbay, Esen] Mersin Univ, Sch Med, Dept Endocrinol & Metab, Mersin, Turkey.[Gul, Kamile] Kahramanmaras Sutcu Imam Univ, Sch Med, Dept Endocrinol & Metab, Kahramanmaras, Turkey.[Agbaht, Kemal] Private Defne Hosp, Dept Endocrinol & Metab, Antalya, Turkey.[Yilmaz, Muge Ozsan] Mustafa Kemal Univ, Sch Med, Dept Endocrinol & Metab, Antakya, Turkey.[Bozkirli, Emre] Baskent Univ, Adana Training Hosp, Dept Endocrinol & Metab, Ankara, Turkey.[Tetiker, B. Tamer; Cetinkaya Altuntas, Seher] Cukurova Univ, Sch Med, Dept Endocrinol & Metab, Adana, Turkey.[Atmaca, Aysegul; Durmus, Elif Tutku] 19 Mayis Univ, Sch Med, Dept Endocrinol & Metab, Samsun, Turkey.[Mete, Turkan] Univ Hlth Sci, Sch Med, Samsun Training & Res Hosp, Dept Endocrinol & Metab, Samsun, Turkey.[Dikbas, Oguz] Giresun Univ, Sch Med, Dept Endocrinol & Metab, Giresun, Turkey.[Akin, Safak] Recep Tayyip Erdogan Univ, Sch Med, Dept Endocrinol & Metab, Rize, Turkey.[Nuhoglu, Irfan; Ersoz, Halil Onder] Karadeniz Tech Univ, Sch Med, Dept Endocrinol & Metab, Trabzon, Turkey.[Bayraktaroglu, Taner] Bulent Ecevit Univ, Sch Med, Dept Endocrinol & Metab, Zonguldak, Turkey.[Sisman, Pinar] Kars Harakani State Hosp, Dept Endocrinol & Metab, Kars, Turkey.[Sahin, Ibrahim; Cetin, Sedat] Inonu Univ, Sch Med, Dept Endocrinol & Metab, Malatya, Turkey.[Capoglu, Ilyas; Akbas, Emin Murat] Erzincan Univ, Sch Med, Dept Endocrinol & Metab, Erzincan, Turkey.[Ucler, Rifki] Yuzuncu Yil Univ, Sch Med, Dept Endocrinol & Metab, Van, Turkey.[Eren, Mehmet Ali] Harran Univ, Sch Med, Dept Endocrinol & Metab, Sanliurfa, Turkey.[Tuzcu, Alpaslan Kemal; Pekkolay, Zafer] Dicle Univ, Sch Med, Dept Endocrinol & Metab, Diyarbakir, Turkey.[Ozkaya, Mesut] Univ Hlth Sci, Sch Med, Gaziantep Ersin Arslan Res & Training Hosp, Gaziantep, Turkey.[Araz, Mustafa] Gaziantep Univ, Sch Med, Dept Endocrinol & Metab, Gaziantep, Turkey.[Salman, Serpil] Liv Hosp Ulus, Dept Endocrinol & Metab, Istanbul, Turkey.[Dizdar, Oguzhan Sitki] Kayseri Educ & Res Hosp, Dept Internal Med, Kayseri, Turkey.[Gurkan, Eren] Mustafa Kemal Univ, Dept Endocrinol & Metab, Antakya, Turkey.[Kargili Carlioglu, Ayse] Erzurum Reg Educ & Res Hosp, Dept Endocrinol & Metab, Erzurum, Turkey

Turkish nationwide survEy of glycemic and other Metabolic parameters of patients with Diabetes mellitus (TEMD study)

AIMS: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus. METHODS: A nationwide, multicenter survey consecutively enrolled patients who were under follow up for at least a year. Optimal control was defined as HbA1c < 7%, home arterial blood pressure (ABP) < 135/85 mmHg, or LDL-C < 100 mg/dL. Achieving all parameters indicated triple metabolic control. RESULTS: HbA1c levels of patients (n = 5211) were 8.6 ± 1.9% (71 ± 22 mmol/mol) and 7.7 ± 1.7% (61 ± 19 mmol/mol), in Type 1 and Type 2 diabetes, respectively. Glycemic control was achieved in 15.3% and 40.2%, and triple metabolic control was achieved in 5.5% and 10.1%, respectively. Only 1.5% of patients met all the criteria of being non-obese, non-smoker, exercising, and under triple metabolic control. Low education level was a significant predictor of poor glycemic control in both groups. CONCLUSIONS: Few patients with Type 2, and even fewer with Type 1 diabetes have optimal metabolic control in Turkey. TEMD study will provide evidence-based information to policy makers to focus more on the quality and sustainability of diabetes care in order to reduce the national burden of the disease

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0–34·5) versus 37·0 years (29·0–49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13–2·38). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH. Funding: Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Societ

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0–34·5) versus 37·0 years (29·0–49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13–2·38). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Homozygous Familial Hypercholesterolaemia International Clinical Collaborators: Tycho R Tromp, Merel L Hartgers, G Kees Hovingh, Antonio J Vallejo-Vaz, Kausik K Ray, Handrean Soran, Tomas Freiberger, Stefano A Bertolini, Mariko Harada-Shiba, Jing Pang, Gerald F Watts, Susanne Greber-Platzer, Martin Mäser, Thomas M Stulnig, Christoph F Ebenbichler, Khalid Bin Thani, David Cassiman, Olivier S Descamps, Daisy Rymen, Peter Witters, Raul D Santos, Liam R Brunham, Gordon A Francis, Jacques Genest, Robert A Hegele, Brooke A Kennedy, Isabelle Ruel, Mark H Sherman, Long Jiang, Luya Wang, Željko Reiner, Vladimir Blaha, Richard Ceska, Jana Dvorakova, Lubomir Dlouhy, Pavel Horak, Vladimir Soska, Lukas Tichy, Robin Urbanek, Helena Vaverkova, Michal Vrablik, Stanislav Zemek, Lukas Zlatohlavek, Sameh Emil, Tarek Naguib, Ashraf Reda, Sophie Béliard, Eric Bruckert, Antonio Gallo, Moses S Elisaf, Genovefa Kolovou, Hofit Cohen, Ronen Durst, Eldad J Dann, Avishay Elis, Osama Hussein, Eran Leitersdorf, Daniel Schurr, Nitika Setia, Ishwar C Verma, Mohammed D Alareedh, Mutaz Al-Khnifsawi, Ali F Abdalsahib Al-Zamili, Sabah H Rhadi, Foaad K Shaghee, Marcello Arca, Maurizio Averna, Andrea Bartuli, Marco Bucci, Paola S Buonuomo, Paolo Calabrò, Sebastiano Calandra, Manuela Casula, Alberico L Catapano, Angelo B Cefalù, Arrigo F G Cicero, Sergio D'Addato, Laura D'Erasmo, Alessia Di Costanzo, Tommaso Fasano, Marta Gazzotti, Antonina Giammanco, Gabriella Iannuzzo, Anastasia Ibba, Emanuele A Negri, Andrea Pasta, Chiara Pavanello, Livia Pisciotta, Claudio Rabacchi, Carlo Ripoli, Tiziana Sampietro, Francesco Sbrana, Fulvio Sileo, Patrizia Suppressa, Patrizia Tarugi, Chiara Trenti, Maria G Zenti, Mika Hori, Mahmoud H Ayesh, Sami T Azar, Fadi F Bitar, Akl C Fahed, Elie M Moubarak, Georges Nemer, Hapizah M Nawawi, Ramón Madriz, Roopa Mehta, Arjen J Cupido, Joep C Defesche, M Doortje Reijman, Jeanine E Roeters-van Lennep, Erik S G Stroes, Albert Wiegman, Linda Zuurbier, Khalid Al-Waili, Fouzia Sadiq, Krzysztof Chlebus, Mafalda Bourbon, Isabel M Gaspar, Katarina S Lalic, Marat V Ezhov, Andrey V Susekov, Urh Groselj, Min-Ji Charng, Weerapan Khovidhunkit, Melih Aktan, Bulent B Altunkeser, Sinan Demircioglu, Melis Kose, Cumali Gokce, Osman Ilhan, Meral Kayikcioglu, Leyla G Kaynar, Irfan Kuku, Erdal Kurtoglu, Harika Okutan, Osman I Ozcebe, Zafer Pekkolay, Saim Sag, Osman Z Salcioglu, Ahmet Temizhan, Mustafa Yenercag, Mehmet Yilmaz, Hamiyet Yilmaz Yasar, Olena Mitchenko, Alexander R M Lyons, Christophe A T Stevens, Julie A Brothers, Lisa C Hudgins, Christina Nguyen, Rano Alieva, Aleksandr Shek, Doan-Loi Do, Ngoc-Thanh Kim, Hong-An Le, Thanh-Tung Le, Mai-Ngoc T Nguyen, Thanh-Huong Truong, Dirk J Blom, Frederick J Raal, Marina Cuchel.Background: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods: The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings: Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5-27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6-18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6-5·8) versus non-high-income countries (9·3 mmol/L, 6·7-12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0-34·5) versus 37·0 years (29·0-49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13-2·38). Interpretation: Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH.Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Society.info:eu-repo/semantics/publishedVersio

Worldwide experience of homozygous familial hypercholesterolaemia: retrospective cohort study

Background Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic characteristics, as well as the impact, of current practice on health outcomes of HoFH patients globally. Methods The HoFH International Clinical Collaborators registry collected data on patients with a clinical, or genetic, or both, diagnosis of HoFH using a retrospective cohort study design. This trial is registered with ClinicalTrials.gov, NCT04815005. Findings Overall, 751 patients from 38 countries were included, with 565 (75%) reporting biallelic pathogenic variants. The median age of diagnosis was 12·0 years (IQR 5·5–27·0) years. Of the 751 patients, 389 (52%) were female and 362 (48%) were male. Race was reported for 527 patients; 338 (64%) patients were White, 121 (23%) were Asian, and 68 (13%) were Black or mixed race. The major manifestations of ASCVD or aortic stenosis were already present in 65 (9%) of patients at diagnosis of HoFH. Globally, pretreatment LDL cholesterol levels were 14·7 mmol/L (IQR 11·6–18·4). Among patients with detailed therapeutic information, 491 (92%) of 534 received statins, 342 (64%) of 534 received ezetimibe, and 243 (39%) of 621 received lipoprotein apheresis. On-treatment LDL cholesterol levels were lower in high-income countries (3·93 mmol/L, IQR 2·6–5·8) versus non-high-income countries (9·3 mmol/L, 6·7–12·7), with greater use of three or more lipid-lowering therapies (LLT; high-income 66% vs non-high-income 24%) and consequently more patients attaining guideline-recommended LDL cholesterol goals (high-income 21% vs non-high-income 3%). A first major adverse cardiovascular event occurred a decade earlier in non-high-income countries, at a median age of 24·5 years (IQR 17·0–34·5) versus 37·0 years (29·0–49·0) in high-income countries (adjusted hazard ratio 1·64, 95% CI 1·13–2·38). Interpretation Worldwide, patients with HoFH are diagnosed too late, undertreated, and at high premature ASCVD risk. Greater use of multi-LLT regimens is associated with lower LDL cholesterol levels and better outcomes. Significant global disparities exist in treatment regimens, control of LDL cholesterol levels, and cardiovascular event-free survival, which demands a critical re-evaluation of global health policy to reduce inequalities and improve outcomes for all patients with HoFH. Funding Amsterdam University Medical Centers, Location Academic Medical Center; Perelman School of Medicine at the University of Pennsylvania; and European Atherosclerosis Societ