High prevalence of cardiac post-acute sequelae in patients recovered from Covid-19. Results from the ARCA post-COVID study.

Background: Many data were published about Long-Covid prevalence, very few about the findings of new cardiac alterations (NCA) in COVID-19-recovered people. ARCA-post-COVID is an observational study designed to investigate the prevalence of NCA in patients recovered from Covid-19.Methods: from June 2020 to December 2022, we enrolled 502 patients with a positive nasopharyngeal swab for SARS-CoV2 and a subsequent negative one. We performed anamnesis, lab-test, and routine cardiological tests (ECG, Holter, TTE). Results: The median age was 56 years (IQR 44-67); women were 52.19%; in the acute phase 24.1% of patients were treated in a medical department, 7.2% in the ICU and the others at home. At the visit, 389 patients (77.49%) complained of a broad range of symptoms. We reported patients' characteristics according to the course of the disease and the persistence of symptoms. NCA were found in 138 patients (27.49%): among them 60 cases (11.95%) of pericardial effusion. Patients with NCA were older (median 60y, IQR: 47-72, vs median 56y, IQR 42-65), had a higher prevalence of smokers (27% vs 17%; p0.014), CAD (11% vs 6%; p0.048) and stroke/TIA (3.6% vs 0.3%; p0.002) and a lower prevalence of hypercholesterolemia (18% vs 30%; p0.007). The prevalence of NCA seems constant with different subtypes of the virus. Conclusion: the prevalence of NCA in patients who recovered from COVID-19 is high and constant since the beginning of the pandemic; it is predictable based on hospitalization and long-lasting symptoms (9.64%-42.52%). Patients with one of these characteristics should undergo cardiological screening.

Alert-LDL-2: adherence to guidelines and goals attainment in the treatment of diabetic patients with dyslipidemia.

BACKGROUND: Type 2 diabetes mellitus is associated with a cluster of lipid and apolipoprotein abnormalities which increase the risk for atherosclerotic cardiovascular disease. The aim of this study was to evaluate the adherence to guidelines-oriented dyslipidemia treatment in diabetic patients and to assess the efficacy of a territorial goal-oriented program. METHODS: One thousand seventy-one diabetic patients at very high cardiovascular risk were enrolled in this prospective study. They performed a clinical-laboratory follow-up program, received lifestyle recommendations and optimization of their antihyperlipidemic therapies. At the beginning and the 3-month follow-up visit, LDL-c data were collected, and further therapies were prescribed to the patients that did not reach the target. After 12 month follow-up, LDL-c data were collected again. RESULTS: Diabetic patients significantly improved mean LDL cholesterol levels during one-year follow-up (LDLc mean value 135 mg/dL at baseline, 60 mg/dL at the end of the study), obtaining a greater reduction compared to non-diabetic patients participating in the same program. Accordingly, the percentage of patients that reached the lipid target was significantly higher in diabetic patients after 3-months and 12- follow-ups (P<0.05). Diabetic patients assuming statins, both in monotherapy and in combination with ezetimibe, increased during the follow-up (74.1% at the enrolment vs. 88.2% one year later). GLP1ra-treated patients achieved the greatest reduction in cholesterol levels compared to baseline. CONCLUSIONS: The results of the study recommend encouraging strategies and appropriate treatments to achieve a targeted lipid profile in diabetic patients at very high cardiovascular risk.

Effects of three-months folate supplementation on early vascular abnormalities in hyperhomocysteinemic patients with epilepsy.

BACKGROUND: Epilepsy has been associated with an increased risk of cardiovascular events. Anti-seizure medication (ASM) may contribute to vascular risk by several mechanisms, including increased homocysteine levels. This study aims to assess the global vascular burden in hyperhomocysteinemic people with epilepsy (PWE) on long-term ASM before and after folic acid supplementation and in subgroups of PWE treated with single enzyme-inducing or single non-enzyme inducing ASM. METHODS: One hundred and seventy-four hyperhomocysteinemic (HHcy) PWE who met the inclusion criteria were enrolled. Carotid Doppler ultrasonography, FMD and ultrasound assessment of the brachial artery properties at the baseline and after 90 days of folic acid supplementation were performed. The vascular biomarkers MMP-9 and TIMP-1 were also detected. RESULTS: After folic acid supplementation, in HHcy patients homocysteine levels reduced from 26.8 ± 10.5 to 20.2 ± 5.3 µmol/L, carotid Intima-Media-Thickness reduced from 0.83+0.06 mm to 0.79±0.05 mm, and FMD, distensibility coefficient and ß-stiffness improved (p < 0.05). Moreover, MMP-9 and TIMP-1 reduced after supplementation (p < 0.05). PWE treated with a single enzyme-inducing ASM showed an impairment of vascular parameters compared to patients treated with non-enzyme inducing ASM. CONCLUSIONS: The results highlight the importance of assessing homocysteine levels and estimating the cardiovascular risk of PWE, preferring non-enzyme inducing ASM in high cardiovascular-risk patients. An adequate correction of homocysteine levels with folate supplementation should be considered to improve the cardiovascular profile.

Clinical outcomes of newly diagnosed, stable angina patients managed according to current guidelines. The ARCA (Arca Registry for Chronic Angina) Registry: A prospective, observational, nationwide study.

BACKGROUND: Clinical outcomes of stable angina patients treated according to guidelines recommendations (medical therapy first, selective revascularization in high risk or unresponsive patients) are not fully known. METHODS AND RESULTS: Eight hundred thirty-three patients with newly diagnosed, stable angina were enrolled in a prospective, observational, nationwide registry and followed for 1 year. Symptoms and quality of life were evaluated with the CCS angina grading, with a self-assessment scale and with the SAQ-7. A composite end-point of MACEs (all-cause death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina) at 1 year was considered. Upon enrollment, all patients were prescribed guidelines directed medical therapy. After one month of therapy, angina relieved or improved in 47% of the overall population. Patients in CCS class I significantly increased from 28.4% at enrollment to 67.1% at 12 months, and the SAQ-7 score from 58.4 ± 20 to 85.9 ± 14. The rate of MACEs was low (2.9%) in the overall population. After one month of medical therapy, 40.6% of patients were referred for coronary angiography and revascularization for resistant symptoms (invasive strategy). Among these, 38.2% had normal coronary arteries and 47% actually underwent revascularization. No difference between invasive and medical groups was found at 12 months in symptoms, quality of life and MACEs, except for a greater improvement in self-assessed symptoms in the invasive group. Combined medical and invasive strategies left 28.5% of patients still symptomatic at the end of the study. CONCLUSIONS: The study confirms the efficacy and safety of a tailored approach to stable angina, as recommended by guidelines, with medical therapy first followed by selective revascularization when needed.

ALERT-LDL: adherence to guidelines in the treatment of patients with dyslipidemia.

The association between LDL-c levels and cardiovascular outcomes suggests tailoring lipid-lowering therapies according to total cardiovascular risk. We aimed to evaluate the adherence to guidelines-oriented dyslipidaemia's treatment in an outpatient population referring to ARCA cardiologists, and assess the efficacy of treatment's optimization for each specific level of risk. Three thousand seventy-five patients enrolled in this prospective study were classified according to cardiovascular risk category, and their therapies were optimized. At the beginning and the 3 month follow-up visit, LDL-c data were collected, and further therapies were prescribed to the patients that did not reach the target. A significant LDL-c reduction was observed in all subgroups at different cardiovascular risk at the end of the study (p < 0.05). The number of patients assuming statins, both in monotherapy and in combination with ezetimibe, increased during the follow-up (63% at the enrollment vs 89% after 12 months). At the enrollment, only 1.4% of patients were treated with PCSK-9 inhibitors while after 12 months the percentage increased both in high (5.8%) and very high-risk (18.4%) patients. At the beginning of the study, only 698/3075 patients (22.7%) reached lipid targets. At the end of the study, carried out by the referring cardiologists in the pertaining healthcare districts and specifically aimed to control the lipid profile, the percentage of patients on target increased in all risk categories (68.5%). Our results suggest carefully implementing measures that encourage outpatients and their cardiologists to achieve the targeted lipid profile according to cardiovascular risk.

Can pulse wave velocity (PWV) alone express arterial stiffness? A neglected tool for vascular function assessment.

Arterial stiffness, defined as the rigidity of the arterial wall, is the consequence of vascular aging and is associated with the full spectrum of cardiovascular diseases. Carotid-femoral pulse wave velocity (cf-PWV) is the gold standard method for arterial stiffness evaluation: it measures the velocity of the arterial pulse along the thoracic and abdominal aorta alongside arterial distensibility. Its value rises as stiffness progresses. Cf-PWV is helpful to assess residual cardiovascular risk (CVR) in hypertension (HT). In fact, an increase in pulsatility and arterial stiffness predicts CVR in patients affected by arterial HT, independently of other risk factors. Arterial stiffness can predict cardiovascular events in several other clinical conditions such as heart failure, diabetes, and pulmonary HT. However, cf-PWV has not been yet included in routine clinical practice so far. A possible reason might be its methodological and theoretical limitations (inaccuracy in the traveled distance, intra and interindividual variability, lack of well-defined references values, and age- and blood pressure-independent cutoff). To exceed these limits a strict adherence to guidelines, use of analytical approaches, and possibility of integrating the results with other stiffness examinations are essential approaches.

Management of patients with chronic heart failure and type 2 diabetes mellitus: the SCODIAC-II study.

SCODIAC was a pilot study which revealed an increasing use of SGLT2i in 123 outpatients affected with Heart Failure (HF) and Type 2 Diabetes Mellitus. SCODIAC-II study, the second phase of the program, has been carried out to determine diagnostic and therapeutic pathways in a larger group of patients and to verify whether the use of innovative antidiabetic therapies could modify echocardiographic parameters and cardiovascular therapies. 406 HF-diabetic patients, referred to Cardiologists and Diabetologists of pertaining healthcare districts in Campania, were enrolled in this retrospective study and divided in Group A, composed of 136 patients with preserved Ejection Fraction (HF-pEF)(> 45%) and Group B, formed of 270 patients with reduced EF (HF-rEF)(≤ 45%). All patients had performed periodic clinical and echocardiographic evaluations. The antidiabetic therapies resulted modified after 1 year with a greater use of GLP1-AR, gliptins and SGLT2i. Cardiovascular therapies resulted also modified with a greater use of sacubitril/valsartan and a reduction of ACEi and ARBs in HF-rEF patients. Echocardiography E velocity, A velocity and E/e' ratio resulted markedly reduced in 25 HF-pEF and in 60 HF-rEF patients treated with SGLT2i, in respect to both the whole sample of subjects at beginning and the other diabetic patients. LAVi resulted reduced only in HF-pEF patients and EF increased only in HF-rEF patients. The approach to the patients with HF and diabetes must necessarily take place in the healthcare districts, be multidisciplinary and integrated. SGLT2i could improve left ventricular function in HF-rEF patients and modify cardiovascular therapies, almost in this setting of patients.Trial registration The protocol was approved by the University of Naples Federico II Ethics Committee and registered at ClinicalTrial.gov (CT04375943). The principles outlined in the Declaration of Helsinki were followed.

Atorvastatin-linked rhabdomyolysis caused by the simultaneous intake of amoxicillin clavulanic acid.

Objectives Rhabdomyolysis is a rare syndrome in which a serious muscle damage suddenly appears, with the possible occurrence of severe complications such as kidney failure, electrolyte imbalances and death, and represents the most severe form of statin-induced muscle injury. Case presentation Here we present the case of a 55-year-old woman who started therapy with amoxicillin clavulanic acid on a background of atorvastatin therapy, resulting in rhabdomyolysis. Conclusions This case highlights the importance of evaluating potential drug interactions in patients taking statin and the need of monitoring clinical and laboratory findings suggestive of rhabdomyolysis.

Peripheral Vascular Function in Dilated Cardiomyopathy of Different Etiology.

Vascular function in dilated cardiomyopathy of different etiology has been poorly investigated. Moreover, reference values of flow-mediated dilation (FMD) in chronic heart failure (CHF) need to be updated according to the new standardized protocols. We characterized the vascular impairment in different stages of post-ischemic dilated cardiomyopathy (PI-DC) or idiopathic dilated cardiomyopathy (I-DC). Eighty consecutive outpatients with CHF in different New York Heart Association (NYHA) classes (45 PI-DC, 35 I-DC) and 50 control subjects underwent FMD and brachial distensibility coefficient measurement. Patients with CHF showed a marked impairment in FMD compared with controls that worsened from classes NYHA I-II to III-IV, independently of etiology (P < .05). New York Heart Association I-II PI-DC patients showed a worse FMD compared with NYHA I-II I-DC patients (P < .05). Brachial distensibility coefficient values were significantly lower in patients with CHF compared with controls (P < .001) without differences between PI-DC and I-DC. In conclusion, advanced CHF is characterized by vascular impairment that is independent of etiology. In the early stages of CHF, endothelial dysfunction is more severe in patients with PI-DC compared with I-DC probably due to the high cardiovascular risk profile. In I-DC, vascular function impairment is independent of cardiovascular risk factors and could participate in the pathogenesis of I-DC.

Adherence to guidelines in the management of patients with chronic heart failure follow-up: role of periodic echocardiographic examinations.

BACKGROUND AND AIM: The Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure trial showed a poor adherence to the current therapeutic guidelines in 660 chronic heart failure (CHF) patients. The second phase, Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure follow-up, was aimed to determine if periodic echocardiographic evaluations could improve the prognosis of CHF patients and/or increase the adherence to the guidelines. MATERIAL AND METHODS: Among 528 CHF patients with reduced ejection fraction from the ALERT registry, 436 patients accepted to participate in the second phase of the study between February and September 2013 and completed the 3-year follow-up phase between February and September 2016. They were randomized into two groups: Group A (n = 218) followed by clinical evaluation and ECG every 3 months, and echocardiography every 6 months and Group B (n = 218) monitored only with clinical evaluation and ECG every 3 months. RESULTS: The number of vascular events that occurred resulted as similar in both the groups: there were 78 hospitalizations (37 in Group A vs. 41 in Group B); 9 home-treated vascular events (4 in Group A and five in Group B); and 16 cardiovascular deaths (9 and 7, respectively). The adherence to the guidelines at the end of the trial resulted as significantly improved in both the groups in comparison with the basal evaluation, without differences between the two groups. CONCLUSION: A strict follow-up of CHF patients was associated with a lower number of events and an improvement in the adherence to the guidelines. Periodic echocardiography does not modify these results.

Long-term follow-up in high risk hypertensive patients with carotid dolicoarteriopathies.

BACKGROUND: Carotid dolicoarteriopathies (CDA) are a common finding during the carotid ultrasound or angiography, but their potential role in the development of cerebrovascular diseases is still unclear. Aim of this study is to clarify the possible relationship between CDA and the occurrence of cerebral events. METHODS: We performed a retrospective analysis on 2124 hypertensive patients with high cardiovascular risk that underwent carotid ultrasound from January 2000 to December 2008. Follow-up data on cerebrovascular events (transient ischemic attack and/or stroke occurrence) at 10 years were collected. RESULTS: The global prevalence of CDA in the study population was 12.9% (274/2124), and carotid kinking was more frequent in females and in the left carotid axis. The percentage of cerebrovascular events among hypertensive patients with CDA was similar to those occurred in the group of patients without CDA (10.94% vs. 10.97%, P=NS), with no differences in the number of strokes (8.39% vs. 8.38% P=NS) and TIA (2.55% vs. 2.59% P=NS). CONCLUSIONS: CDA are not associated with a major occurrence of cerebrovascular events in a high-risk population of hypertensives.

Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism.

OBJECTIVE: To investigate the effect of levothyroxine (L-T4) treatment on early markers of atherosclerotic disease in children with mild idiopathic subclinical hypothyroidism (SH). DESIGN: Two-year, open, case-control prospective study. METHODS: A total of 39 children, aged 9.18±3.56 years, with SH and 39 healthy controls were enrolled in the study. Waist-to-height ratio (WHtR), blood pressure, triglycerides, total cholesterol (total-C), HDL-C, LDL-C, non-HDL-C, triglycerides/HDL-C, atherogenic index (AI), homocysteine (Hcy), asymmetric dimethylarginine (ADMA), flow-mediated dilation (FMD) and intima-media thickness (IMT) were evaluated at baseline and after 2 years of L-T4 treatment in SH children and after 2 years of follow-up in controls. RESULTS: At study entry WHtR was higher in SH subjects compared with controls (0.56±0.08 vs 0.49±0.07, P=0.04) and significantly decreased after 2 years of treatment (0.50±0.06, P<0.0001). Mean HDL-C levels (50.47±11.43 vs 61.06±13.83mg/dL, P=0.002) were lower, while triglycerides/HDL-C (1.63±1.07 vs 1.19±0.69, P=0.05), AI (3.32±0.90 vs 2.78±0.68, P=0.005), and Hcy (9.35±2.61 vs 7.71±1.94µmol/L, P=0.01) were higher in SH subjects compared with controls and improved after 2 years of treatment (HDL-C 56.26±13.76mg/dL, P<0.0001; triglycerides/HDL-C 1.23±0.78, P=0.006; AI 2.82±0.68, P<0.0001; and Hcy 8.25±2.09µmol/L, P=0.06). ADMA concentrations at baseline were higher in SH subjects compared with controls (0.77±0.21 vs 0.60±0.16µmol/L, P=0.001) and decreased after therapy (0.58±0.13µmol/L, P<0.0001). FMD, IMT and other metabolic parameters were not different among SH subjects and controls at baseline and after 2 years. CONCLUSIONS: Children with SH may have subtle pro-atherogenic abnormalities. Although L-T4 treatment exerts some beneficial effects, the long-term impact of therapy on metabolic outcomes in SH children still remains unclear.

Mesoglycan improves vascular reactivity and insulin sensitivity in patients with metabolic syndrome.

OBJECTIVES: The aim of this study was to evaluate the acute and chronic effects of mesoglycan on the endothelial function and arterial elastic properties in patients with metabolic syndrome (MetS). BACKGROUND: MetS is defined by a clustering of vascular risk factors that demand both pharmacologic and non-pharmacologic interventions, including body weight reductions and physical activity. The correction of endothelial dysfunction and arterial wall distensibility associated with MetS have lately received increasing interest. METHODS: Thirty consecutive ambulatory patients affected by MetS were 2:1 randomized in a double-blind fashion to receive mesoglycan or placebo, respectively. In the first phase of the study, we evaluated the acute effects of a single i.m. administration of mesoglycan (60 mg) or placebo on vascular reactivity, as assessed by brachial flow-mediated dilation (FMD). Then, patients were chronically treated with mesoglycan per os (50 mg twice a day) or placebo for 90 days. At the end of this period, vascular reactivity and the arterial wall elastic properties were evaluated. RESULTS: In the mesoglycan group, FMD increased above baseline after acute administration, with a maximum increment of 52% after 2 h. FMD was also significantly greater than baseline after 90 days of chronic treatment. In the placebo group, FMD was unaffected by both acute and chronic mesoglycan administration. Moreover, after 90 days of mesoglycan treatment, a marked improvement in arterial distensibility and compliance was detected and arterial stiffness reduced significantly. CONCLUSIONS: This small, preliminary study shows that mesoglycan exerts relevant effects on vascular physiology, both in an acute setting as well as after prolonged, three-month treatment, in patients affected by metabolic syndrome.

ALERT-HF: adherence to guidelines in the treatment of patients with chronic heart failure.

BACKGROUND: The prognosis of chronic heart failure (CHF) may be substantially improved by strict adherence to current therapeutic guidelines. AIM AND METHODS: To assess the adherence to current guidelines, 660 CHF patients consecutively referred to the ARCA (Associazioni Regionali Cardiologi Ambulatoriali Campania) cardiologists were evaluated. As indicators of adherence to the guidelines, we considered use of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers, beta-blockers, loop diuretics, aldosterone antagonists, digoxin, anticoagulant therapy, and implantation of cardiac devices. RESULTS: The adherence to guidelines has been characterized in patients with reduced ejection fraction, who represent the majority in the ALERT-HF (Adherence to Guidelines in the Treatment of patients with Chronic Heart Failure) trial and in whom the current guidelines are well defined and shared. Among 528 patients affected by CHF with ejection fraction 45% or less, 399 (75.6%) were treated with a beta-blocker, 282 (53.4%) received an angiotensin-converting enzyme inhibitor and 199 (37.7%) an angiotensin receptor blocker. Four hundred and sixty-nine patients (88.9%) used loop diuretics, but only 163 patients (30.9%) an aldosterone antagonist. Among 148 patients with atrial fibrillation, 95 (64.2%) were treated with anticoagulants. As few as 31 patients received cardiac electrical stimulation devices: 10 patients were implanted with a cardioverter-defibrillator and 21 received a device for cardiac resynchronization therapy. CONCLUSION: The study reveals poor adherence to current therapeutic guidelines for CHF, particularly with regard to aldosterone antagonists and anticoagulant therapy in the presence of atrial fibrillation. Even poorer is the adherence to guidelines as regards the use of implantable cardiac devices. The underlying reasons are discussed in relation to the data of other registries.

[Healthcare networks for chronic heart failure management]. / La rete assistenziale per lo scompenso cardiaco cronico.

Chronic heart failure (CHF) is one of the leading causes of disability in the older population. In addition, the management of older CHF patients is particularly complex not only in cases of exacerbations, usually treated in the emergency department, but also in daily clinical practice, where a large commitment from the family and the presence of an accessible competent healthcare district are required. The management of CHF should include a network providing adequate follow-up of older patients and implement the continuity of care from hospital to territory. An adequate integration between hospital and territory can be obtained with a multilevel system made by a first territorial level (outpatient cardiologists and general practitioners), a second level for the treatment of exacerbations (day-hospital or full hospitalization), and a third level, characterized by the availability of comprehensive means for complex examinations and advanced treatments (academic or high-level specialized hospitals). The three levels identified should operate as a single, integrated unit in which all staff members operate synergistically, along common diagnostic and therapeutic pathways, established and shared according to the current guidelines for the treatment of older CHF patients.

Management of chronic heart failure: Role of home echocardiography in monitoring care programs.

AIM: To identify a possible role of home echocardiography for monitoring chronic heart failure (CHF) patients. METHODS: We prospectively investigated 118 patients hospitalized during the last year for CHF who could not easily reach the pertaining District Healthcare Center. The patients were followed up with 2 home management programs: one including clinical and electrocardiographic evaluations and also periodic home echocardiographic examinations (group A), the other including clinical and electrocardiographic evaluations only (group B). RESULTS: At the end of the 18-mo follow-up no signi-ficant differences were observed between the 2 groups as regards the primary endpoint: rehospitalization occurred in 4 patients of the group A and in 6 patients of the group B; major cardiovascular events occurred in 2 and in 3 patients, respectively. No significant differences were observed with respect to the secondary endpoints: one vascular event appeared in both the groups, 3 cardiovascular deaths occurred in group A and 2 in group B. No significant differences were observed between the 2 groups as regards the composite endpoint of death plus hospitalization. CONCLUSION: Home echocardiography for monitoring of CHF patients does not improve the cardiovascular endpoints. In our CHF patients, a low incidence of vascular events was observed.

Impaired diastolic function in naïve untreated human immunodeficiency virus infected patients.

AIM: To evaluate cardiac function and structure in untreated human immunodeficiency virus (HIV) patients without clinical evidence of cardiovascular disease. METHODS: Fifty-three naïve untreated HIV-infected patients and 56 healthy control subjects underwent clinical assessment, electrocardiography (ECG) and echocardiography, including tissue doppler imaging. Moreover, a set of laboratory parameters was obtained from all subjects, including HIV-RNA plasma levels, CD4 cell counts and tumor necrosis factor-α levels. RESULTS: The two groups showed normal ECG traces and no differences regarding systolic morphologic parameters. In contrast, a higher prevalence of left ventricular diastolic dysfunction (abnormal relaxation or pseudonormal filling pattern) was found in the HIV patients (36% vs 9% in patients and controls, respectively, P <0.001). CONCLUSION: Subclinical cardiac abnormalities appear in an early stage of the HIV infection, independent of antiretroviral therapy. The data suggest that HIV per se plays a role in the genesis of diastolic dysfunction.

Effects of long-term L-thyroxine treatment on endothelial function and arterial distensibility in young adults with congenital hypothyroidism.

OBJECTIVE: Patients with congenital hypothyroidism (CH) display subclinical abnormalities of the cardiovascular system that are related to unphysiological fluctuations of TSH levels and occur despite careful replacement therapy. DESIGN: The aim of the present case-control study was to evaluate the effects of long-term levothyroxine (l-T(4)) replacement therapy on the vascular district in CH patients by assessing endothelial function with flow-mediated dilation (FMD) and brachial artery distensibility with the measurement of the coefficient of distensibility (DC). METHODS: Thirty-two young adults with CH aged 18.9+/-0.2 years and 32 age- and sex-matched controls underwent brachial Doppler ultrasound examination to measure FMD and DC at the time of the study. Hypothyroidism was diagnosed by neonatal screening, and l-T(4) treatment was initiated within the first month of life. RESULTS: Compared to healthy controls, CH patients had significantly reduced brachial artery reactivity with lower FMD values (8.9+/-5.7 vs 14.1+/-5.1% P=0.003) and decreased vascular distensibility (24.6+/-1.6 vs 27.3+/-3 kPa(-1)x10(-3), P<0.0002). Linear regression analysis revealed that both total and pubertal mean TSH and number of episodes of undertreatment were independent determinants of FMD and DC. Pubertal mean TSH was the best predictor of both FMD and DC (r=0.81 and r=0.87 respectively, P<0.001). CONCLUSIONS: Young adults with CH treated with long-term l-T(4) replacement therapy may have significant impairment of both FMD and DC. Our data suggest that high TSH levels, inadequately corrected by l-T(4) replacement therapy in CH patients especially during puberty, can exert significant effects on the elastic and functional vessel properties.