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Background: Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase genes (SDHx) are at risk of developing tumors, including paragangliomas, gastrointestinal stromal tumors, and renal cell carcinomas. Early tumor detection is paramount for improved clinical outcome. Blood-based biomarkers could aid in identifying individuals with PVs early and provide functional evidence in patients with variants of unknown significance. Methods: Blood plasma, urine, peripheral blood mononuclear cells, and erythrocytes from patients with and without SDHx PVs were investigated for central carbon metabolites. These were measured by liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy and included among others, succinate, fumarate, α-ketoglutarate, and lactate. Results: Plasma succinate to fumarate ratios effectively distinguished tumor-bearing and asymptomatic patients with and without SDHx PV with promising diagnostic performance (areas under the receiver operating characteristic curve 0.86-0.95), although higher levels were noted in individuals with SDHB PV. Metabolites in urine and in peripheral blood mononuclear cell extracts were largely similar between groups. Erythrocytes showed strong metabolic alterations in patients with SDHx PV compared to controls, with 8 of 13 low-molecular organic acids being significantly different (P < .05). The lactate-α-ketoglutarate-ratio of erythrocytes identified individuals with SDHx PV equally well as plasma, with a sensitivity and specificity of 92% (AUC 0.97). Conclusion: Blood biomarkers have been underutilized for identifying carriers of SDHx PV or to validate variants of unknown significance. Our findings advocate for further investigation into a combined approach involving plasma and erythrocytes for future diagnostic strategies.
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INTRODUCTION: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality. METHODS AND ANALYSIS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland. ETHICS AND DISSEMINATION: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences. PROTOCOL VERSION NUMBER: 01-15 November 2022. TRIAL REGISTRATION NUMBER: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.
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Alopurinol , COVID-19 , Doenças Cardiovasculares , Humanos , Alopurinol/uso terapêutico , Método Duplo-Cego , Doenças Cardiovasculares/prevenção & controle , COVID-19/complicações , Idoso , Pessoa de Meia-Idade , Masculino , SARS-CoV-2 , Feminino , Adulto , Síndrome de COVID-19 Pós-Aguda , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco de Doenças CardíacasRESUMO
Despite substantial progress in understanding the complex pathophysiology, hypertension remains a serious public health challenge affecting over 1.2 billion adults aged 30-79 years worldwide. Appropriate knowledge of the different pharmaceutical classes of antihypertensive agents and an understanding of the characteristics of individual molecules are essential to optimize clinical outcomes in patients with hypertension. We conducted a computer-assisted web interviewing (CAWI) quantitative survey in Italy, Poland, and Turkey to investigate physicians' prescriptions, knowledge, and perceptions of antihypertensive drugs with a focus on ß-blockers, to assess antihypertensive usage patterns and the reasons underlying prescription choices. The survey findings show that ß-blockers retain a pivotal role in the management of hypertension and are prescribed more often for patients with cardiovascular comorbidities than for patients with diabetic comorbidities. In all three countries, nebivolol is the only ß-blocker among the ones analyzed which is consistently prescribed to 20% or more of patients and is overall the most prescribed one for the population with comorbid diabetes. In terms of specific ß-blockers' features, this study revealed knowledge gaps that underline the need for educational activities focused on the differences among ß-blockers, which are important in choosing the most suitable agent for individualized antihypertensive therapy.
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Antagonistas Adrenérgicos beta , Anti-Hipertensivos , Hipertensão , Padrões de Prática Médica , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Turquia/epidemiologia , Pessoa de Meia-Idade , Polônia/epidemiologia , Itália/epidemiologia , Masculino , Feminino , Adulto , Padrões de Prática Médica/estatística & dados numéricos , Anti-Hipertensivos/uso terapêutico , Idoso , Conhecimentos, Atitudes e Prática em Saúde , Atitude do Pessoal de Saúde , Nebivolol/uso terapêutico , Inquéritos e Questionários , Médicos/estatística & dados numéricos , Médicos/psicologiaRESUMO
We describe herein the European Reference Network on Rare Endocrine Conditions clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, paediatric endocrinology, and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series. The guideline includes a brief description of the genetics and molecular pathophysiology associated with each condition, the patients to be screened, and how to screen. Diagnostic and treatment approaches for patients with genetically determined diagnosis are presented. The recommendations apply to patients with genetically proven familial hyperaldosteronism and not to families with more than one case of primary aldosteronism without demonstration of a responsible pathogenic variant.
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Hiperaldosteronismo , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Hiperaldosteronismo/terapia , Humanos , Europa (Continente) , Doenças Raras/diagnóstico , Doenças Raras/genética , Doenças Raras/terapiaRESUMO
Malignant hypertension (MHT) is a hypertensive emergency with excessive blood pressure (BP) elevation and accelerated disease progression. MHT is characterized by acute microvascular damage and autoregulation failure affecting the retina, brain, heart, kidney, and vascular tree. BP must be lowered within hours to mitigate patient risk. Both absolute BP levels and the pace of BP rise determine risk of target-organ damage. Nonadherence to the antihypertensive regimen remains the most common cause for MHT, although antiangiogenic and immunosuppressant therapy can also trigger hypertensive emergencies. Depending on the clinical presentation, parenteral or oral therapy can be used to initiate BP lowering. Evidence-based outcome data are spotty or lacking in MHT. With effective treatment, the prognosis for MHT has improved; however, patients remain at high risk of adverse cardiovascular and kidney outcomes. In this review, we summarize current viewpoints on the epidemiology, pathogenesis, and management of MHT; highlight research gaps; and propose strategies to improve outcomes.
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Hipertensão Maligna , Humanos , Hipertensão Maligna/epidemiologia , Hipertensão Maligna/fisiopatologia , Hipertensão Maligna/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologiaRESUMO
Introduction: Endocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing's syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT. Methods: Retrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus. Results: After adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites - 18 in PPGL, 15 in CS, and 23 in PA - were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites. Discussions: Our study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL's metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.
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Neoplasias das Glândulas Suprarrenais , Cortisona , Síndrome de Cushing , Diabetes Mellitus , Hipertensão , Paraganglioma , Feocromocitoma , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Hidrocortisona/metabolismo , Estudos Retrospectivos , Síndrome de Cushing/complicações , Esteroides , Neoplasias das Glândulas Suprarrenais/complicações , Hipertensão/complicações , Feocromocitoma/complicações , Paraganglioma/complicações , Catecolaminas , DesidroepiandrosteronaRESUMO
BACKGROUND: Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA). METHODS: Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others. Disease classifications were not achieved in 106 patients. Areas under receiver-operating characteristic curves (AUROC) and other measures were used to compare diagnostic performance. RESULTS: Mass spectrometry-based measurements yielded lower plasma aldosterone concentrations than immunoassay measurements. For the ARR based on immunoassay measurements of aldosterone, AUROCs were slightly lower (P = 0.018) than those using mass spectrometry measurements (0.895 vs 0.906). The cutoff for the ARR to reach a sensitivity of 95% was 30 and 21.5â pmol/mU by respective immunoassay and mass spectrometry-based measurements, which corresponded to specificities of 57% for both. With data restricted to patients with unilateral PA, diagnostic sensitivities of 94% with specificities >81% could be achieved at cutoffs of 68 and 52â pmol/mU for respective immunoassay and mass spectrometry measurements. CONCLUSIONS: Mass spectrometry-based measurements of aldosterone for the ARR provide no clear diagnostic advantage over immunoassay-based measurements. Both approaches offer limited diagnostic accuracy for the ARR as a screening test. One solution is to employ the higher cutoffs to triage patients likely to have unilateral PA for further tests and possible adrenalectomy, while using the lower cutoffs to identify others for targeted medical therapy.German Clinical Trials Register ID: DRKS00017084.
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Aldosterona , Hiperaldosteronismo , Espectrometria de Massas , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/sangue , Aldosterona/sangue , Imunoensaio/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Espectrometria de Massas/métodos , Sensibilidade e Especificidade , Curva ROC , Adulto , Renina/sangue , Idoso , Programas de Rastreamento/métodosAssuntos
Pressão Sanguínea , Oclusão Coronária , Frequência Cardíaca , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Doença Crônica , Oclusão Coronária/fisiopatologia , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Fatores de Tempo , Resultado do Tratamento , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
We address the reasons why, unlike other guidelines, in the 2023 guidelines of the European Society of Hypertension ß-blockers (BBs) have been regarded as major drugs for the treatment of hypertension, at the same level as diuretics, calcium channel blockers, and blockers of the renin-angiotensin system. We argue that BBs, (1) reduce blood pressure (the main factor responsible for treatment-related protection) not less than other drugs, (2) reduce pooled cardiovascular outcomes and mortality in placebo-controlled trials, in which there has also been a sizeable reduction of all major cause-specific cardiovascular outcomes, (3) have been associated with a lower global cardiovascular protection in 2 but not in several other comparison trials, in which the protective effect of BBs versus the other major drugs has been similar or even greater, with a slightly smaller or no difference of global benefit in large trial meta-analyses and a similar protective effect when comparisons extend to BBs in combination versus other drug combinations. We mention the large number of cardiac and other comorbidities for which BBs are elective drugs, and we express criticism against the exclusion of BBs because of their lower protective effect against stroke in comparison trials, because, for still uncertain reasons, differences in protection against cause-specific events (stroke, heart failure, and coronary disease) have been reported for other major drugs. These partial data cannot replace global benefits as the main deciding factor for drug choice, also because in the general hypertensive population whether and which type of event might occur is unknown.
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Doença da Artéria Coronariana , Hipertensão , Acidente Vascular Cerebral , Humanos , Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Hipertensão/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controleRESUMO
BACKGROUND: Secondary hypertension (SH) is a form of high blood pressure caused by an identifiable underlying condition. Although, it accounts for a small fraction of the overall hypertensive population, detection and management of SH is of utmost importance, because SH phenotypes carry a high cardiovascular risk and can possibly be cured by timely treatment. CONTENT: This review focuses on the endocrine causes of SH, such as primary aldosteronism, Cushing syndrome, thyroid disease, pheochromocytoma and paraganglioma, acromegaly, and rare monogenic forms. It discusses current biomarkers, analytical methods, and diagnostic strategies, highlighting advantages and limitations of each approach. It also explores the emerging -omics technologies that can provide a comprehensive and multidimensional assessment of SH and its underlying mechanisms. SUMMARY: Endocrine SH is a heterogeneous and complex condition that requires proper screening and confirmatory tests to avoid diagnostic delays and improve patient outcomes. Careful biomarker interpretation is essential due to potential interferences, variability, and method-dependent differences. Liquid chromatography-tandem mass spectrometry is a superior method for measuring low-concentration hormones and metabolites involved in SH, but it requires expertise. Omics approaches have great potential to identify novel biomarkers, pathways, and targets for SH diagnosis and treatment, especially considering its multifactorial nature.
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Biomarcadores , Hipertensão , Humanos , Hipertensão/diagnóstico , Doenças do Sistema Endócrino/diagnóstico , Hiperaldosteronismo/diagnóstico , Feocromocitoma/diagnóstico , Síndrome de Cushing/diagnósticoRESUMO
In June 2023, the European Society of Hypertension (ESH) presented and published the new 2023 ESH Guidelines for the Management of Arterial Hypertension, a document that was endorsed by the European Renal Association (ERA). Following the evolution of evidence in recent years, several novel recommendations relevant to the management of hypertension in patients with chronic kidney disease (CKD) appeared in these Guidelines. These include recommendations for target office blood pressure (BP) <130/80 mmHg in most and against target office BP <120/70 mmHg in all patients with CKD; recommendations for use of spironolactone or chlorthalidone for patients with resistant hypertension with estimated glomerular filtration rate (eGFR) higher or lower than 30 mL/min/1.73 m2, respectively; use of a sodium-glucose cotransporter 2 inhibitor for patients with CKD and estimated eGFR ≥20 mL/min/1.73 m2; use of finerenone for patients with CKD, type 2 diabetes mellitus, albuminuria, eGFR ≥25 mL/min/1.73 m2 and serum potassium <5.0 mmol/L; and revascularization in patients with atherosclerotic renovascular disease and secondary hypertension or high-risk phenotypes if stenosis ≥70% is present. The present report is a synopsis of sections of the ESH Guidelines that are relevant to the daily clinical practice of nephrologists, prepared by experts from ESH and ERA. The sections summarized are those referring to the role of CKD in hypertension staging and cardiovascular risk stratification, the evaluation of hypertension-mediated kidney damage and the overall management of hypertension in patients with CKD.
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Hipertensão , Nefrologia , Guias de Prática Clínica como Assunto , Sociedades Médicas , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Nefrologia/normas , Europa (Continente) , Anti-Hipertensivos/uso terapêutico , Insuficiência Renal Crônica/complicaçõesRESUMO
INTRODUCTION: The 2018 European Society of Cardiology / European Society of Hypertension guidelines recommended the use of combination therapy, especially in the form of singlepill combinations (SPCs), for treatment of hypertension. OBJECTIVES: We assessed adherence to these recommendations after their publication and during the COVID19 pandemic in Poland. PATIENTS AND METHODS: The frequencies of using individual antihypertensive drug classes and their combinations were analyzed for the years 2019, 2020, and 2021 in all patients who filled at least 1 prescription for an antihypertensive drug, using information from a database covering all prescriptions filled in Poland. RESULTS: In the years 2019, 2020, and 2021, a total of 10 328 341, 9 478 949, and 9 637 595 patients, respectively, fulfilled the inclusion criteria. There was a continuous decrease in the rate of patients meeting the criteria for coprescribing 2 or more antihypertensive drugs in the consecutive years (59.3%, 49%, 45.6%, respectively, in 2019, 2020, and 2021; P <0.001). In 2019, 2020, and 2021, a combination of reninangiotensin system blockers, calcium channel blockers and / or diuretics was respectively used by 41.7%, 40.9%, and 42% of the patients taking 2 antihypertensive drugs (P <0.001), and by 15.2%, 17.2%, and 18.5% of the patients taking 3 antihypertensive drugs (P <0.001). There was an increase in the use of ßblockers over the study period (62%, 62.8%, and 63.7%, respectively, in 2019, 2020, and 2021; P <0.001). Double SPCs were used by 28%, 28.7%, and 29.8% of the patients (P <0.001), and triple SPCs by 2.6%, 2.9%, and 3.4% of the patients (P <0.001), respectively, in 2019, 2020, and 2021. CONCLUSIONS: During the COVID19 pandemic, a decrease in the frequency of combination treatments and an increase in the frequency of dual and triple SPC use were observed. Despite the slow increase in the frequency of prescribing the guidelinerecommended drug combinations, their use remains suboptimal.
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COVID-19 , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Polônia , Pandemias , Hipertensão/tratamento farmacológicoRESUMO
No abstract available.