The Influence of Cardiovascular Risk Factors and Hypogonadism on Cardiac Outcomes in an Aging Population of Beta-Thalassemia Patients

Barbero, Umberto; Ajassa, Matteo; Gaglioti, Carmen Maria; Piga, Antonio; Longo, Filomena

doi:10.3390/jcdd9010003

Cited by 5 publications

(9 citation statements)

References 31 publications

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“…Adequate awareness of cardiovascular disease is a prerequisite for the adoption of preventive actions and healthy behaviors, and it is particularly important for TM patients due to the heavy burden of CVD, which is associated with multiple causes (myocardial iron overload, traditional cardiovascular risk factors, cardiovascular inflammation, and fibrosis) [10][11][12][13][14]. This is the first study evaluating gender differences in knowledge and awareness of CVDs, knowledge of CVRFs and preventive measures, and perception of health status among Italian patients with TM.…”

Section: Discussionmentioning

confidence: 99%

“…Besides MIO, in TM, heart disease can also result from other causes such as chronic anemia, endocrine abnormalities [10,11], nutritional deficiencies, and genetic factors [12,13]. It has been shown that in TM diabetes mellitus significantly increases the risk for heart failure (HF), hyperkinetic arrhythmias, and myocardial fibrosis, independently from MIO [11].…”

Section: Introductionmentioning

confidence: 99%

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Gender Differences in Knowledge and Perception of Cardiovascular Disease among Italian Thalassemia Major Patients

Meloni

Pistoia

Maffei

et al. 2022

JCM

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We evaluated gender differences in knowledge and perception of cardiovascular disease (CVD) among Italian thalassemia major (TM) patients. An anonymous questionnaire was completed by 139 β-TM patients (87 (62.7%) females, 40.90 ± 8.03 years). Compared to females, males showed a significantly higher frequency of CVDs, and they less frequently selected tumors in general as the greatest health problem for people of the same age and gender (48.1% vs. 66.7%; p = 0.031) and as the greatest danger to their future health (26.9% vs. 43.7%; p = 0.048). CVDs were designated as the greatest danger to their future health by a significantly higher percentage of males than females (53.8% vs. 36.8%; p = 0.048). Both males and females showed a good knowledge of cardiovascular risk factors and preventive measures for CVDs. No gender differences were detected in the subjective well-being and the perceived cardiovascular risk. The perceived risk was not influenced by age, presence of cardiovascular risk factors, or disease, but no patient with a low perceived CVD risk had myocardial iron overload. Our findings highlight the need to implement future educational programs aimed at increasing the awareness of CVD as the greatest health issue, especially among the female TM population, and at informing TM patients of the different actors, besides iron, that play a role in the development of cardiovascular complications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gender Differences in Knowledge and Perception of Cardiovascular Disease among Italian Thalassemia Major Patients

Meloni

Pistoia

Maffei

et al. 2022

JCM

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“…Its prevalence varies among studies, related especially to whether or not the pubertal status is taken into consideration. Long-term hypogonadism induces a high cardiovascular risk in addition to toxic effects of cardiac IO [ 53 ]. According to one study, the prevalence is 23.6% among patients at puberty age, and ferritin negatively correlates with pituitary volume [ 27 ].…”

Section: Thalassemic Endocrine Diseasementioning

confidence: 99%

New Entity—Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement

et al. 2022

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Beta-thalassemia (BTH), a recessively inherited haemoglobin (Hb) disorder, causes iron overload (IO), extra-medullary haematopoiesis and bone marrow expansion with major clinical impact. The main objective of this review is to address endocrine components (including aspects of reproductive health as fertility potential and pregnancy outcome) in major beta-thalassemia patients, a complex panel known as thalassemic endocrine disease (TED). We included English, full-text articles based on PubMed research (January 2017–June 2022). TED includes hypogonadism (hypoGn), anomalies of GH/IGF1 axes with growth retardation, hypothyroidism (hypoT), hypoparathyroidism (hypoPT), glucose profile anomalies, adrenal insufficiency, reduced bone mineral density (BMD), and deterioration of microarchitecture with increased fracture risk (FR). The prevalence of each ED varies with population, criteria of definition, etc. At least one out of every three to four children below the age of 12 y have one ED. ED correlates with ferritin and poor compliance to therapy, but not all studies agree. Up to 86% of the adult population is affected by an ED. Age is a positive linear predictor for ED. Low IGF1 is found in 95% of the population with GH deficiency (GHD), but also in 93.6% of persons without GHD. HypoT is mostly pituitary-related; it is not clinically manifested in the majority of cases, hence the importance of TSH/FT4 screening. HypoT is found at any age, with the prevalence varying between 8.3% and 30%. Non-compliance to chelation increases the risk of hypoT, yet not all studies confirmed the correlation with chelation history (reversible hypoT under chelation is reported). The pitfalls of TSH interpretation due to hypophyseal IO should be taken into consideration. HypoPT prevalence varies from 6.66% (below the age of 12) to a maximum of 40% (depending on the study). Serum ferritin might act as a stimulator of FGF23. Associated hypocalcaemia transitions from asymptomatic to severe manifestations. HypoPT is mostly found in association with growth retardation and hypoGn. TED-associated adrenal dysfunction is typically mild; an index of suspicion should be considered due to potential life-threatening complications. Periodic check-up by ACTH stimulation test is advised. Adrenal insufficiency/hypocortisolism status is the rarest ED (but some reported a prevalence of up to one third of patients). Significantly, many studies did not routinely perform a dynamic test. Atypical EM sites might be found in adrenals, mimicking an incidentaloma. Between 7.5–10% of children with major BTH have DM; screening starts by the age of 10, and ferritin correlated with glycaemia. Larger studies found DM in up to 34%of cases. Many studies do not take into consideration IGF, IGT, or do not routinely include OGTT. Glucose anomalies are time dependent. Emerging new markers represent promising alternatives, such as insulin secretion-sensitivity index-2. The pitfalls of glucose profile interpretation include the levels of HbA1c and the particular risk of gestational DM. Thalassemia bone disease (TBD) is related to hypoGn-related osteoporosis, renal function anomalies, DM, GHD, malnutrition, chronic hypoxia-induced calcium malabsorption, and transplant-associated protocols. Low BMD was identified in both paediatric and adult population; the prevalence of osteoporosis/TBD in major BTH patients varies; the highest rate is 40–72% depending on age, studied parameters, DXA evaluation and corrections, and screening thoracic–lumbar spine X-ray. Lower TBS and abnormal dynamics of bone turnover markers are reported. The largest cohorts on transfusion-dependent BTH identified the prevalence of hypoGn to be between 44.5% and 82%. Ferritin positively correlates with pubertal delay, and negatively with pituitary volume. Some authors appreciate hypoGn as the most frequent ED below the age of 15. Long-term untreated hypoGn induces a high cardiovascular risk and increased FR. Hormonal replacement therapy is necessary in addition to specific BTH therapy. Infertility underlines TED-related hormonal elements (primary and secondary hypoGn) and IO-induced gonadal toxicity. Males with BTH are at risk of infertility due to germ cell loss. IO induces an excessive amount of free radicals which impair the quality of sperm, iron being a local catalyser of ROS. Adequate chelation might improve fertility issues. Due to the advances in current therapies, the reproductive health of females with major BTH is improving; a low level of statistical significance reflects the pregnancy status in major BTH (limited data on spontaneous pregnancies and growing evidence of the induction of ovulation/assisted reproductive techniques). Pregnancy outcome also depends on TED approach, including factors such as DM control, adequate replacement of hypoT and hypoPT, and vitamin D supplementation for bone health. Asymptomatic TED elements such as subclinical hypothyroidism or IFG/IGT might become overt during pregnancy. Endocrine glands are particularly sensitive to iron deposits, hence TED includes a complicated puzzle of EDs which massively impacts on the overall picture, including the quality of life in major BTH. The BTH prognostic has registered progress in the last decades due to modern therapy, but the medical and social burden remains elevated. Genetic counselling represents a major step in approaching TH individuals, including as part of the pre-conception assessment. A multidisciplinary surveillance team is mandatory.

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“…It presents with hemolytic anemia caused by abnormalities in the synthesis of beta chains of hemoglobin [ 98 ]. Despite the presence of anemia, which is caused by ineffective erythropoiesis, elevated iron and ferritin levels are observed [ 99 ]. Such disruptions of iron metabolism are caused by the necessity of life-long blood transfusions in the patient [ 99 ].…”

Section: Iron Metabolism Disorders As the Trigger Of Oxidative Stressmentioning

confidence: 99%

“…Despite the presence of anemia, which is caused by ineffective erythropoiesis, elevated iron and ferritin levels are observed [ 99 ]. Such disruptions of iron metabolism are caused by the necessity of life-long blood transfusions in the patient [ 99 ]. Kukongviriyapan et al, while conducting a study among 22 patients suffering from beta thalassemia, proposed that the auto-oxidation of excess beta globin chains and iron accumulation leads to oxidative stress and subsequent tissue and organ damage [ 100 ].…”

Section: Iron Metabolism Disorders As the Trigger Of Oxidative Stressmentioning

confidence: 99%

Vascular Aging and Damage in Patients with Iron Metabolism Disorders

et al. 2022

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Vascular aging is a physiological, multifactorial process that involves every type of vessel, from large arteries to microcirculation. This manifests itself as impaired vasomotor function, altered secretory phenotype, deteriorated intercellular transport function, structural remodeling, and aggravated barrier function between the blood and the vascular smooth muscle layer. Iron disorders, particularly iron overload, may lead to oxidative stress and, among other effects, vascular aging. The elevated transferrin saturation and serum iron levels observed in iron overload lead to the formation of a non-transferrin-bound iron (NTBI) fraction with high pro-oxidant activity. NTBI can induce the production of reactive oxygen species (ROS), which induce lipid peroxidation and mediate iron-related damage as the elements of oxidative stress in many tissues, including heart and vessels’ mitochondria. However, the available data make it difficult to precisely determine the impact of iron metabolism disorders on vascular aging; therefore, the relationship requires further investigation. Our study aims to present the current state of knowledge on vascular aging in patients with deteriorated iron metabolism.

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The Influence of Cardiovascular Risk Factors and Hypogonadism on Cardiac Outcomes in an Aging Population of Beta-Thalassemia Patients

Cited by 5 publications

References 31 publications

Gender Differences in Knowledge and Perception of Cardiovascular Disease among Italian Thalassemia Major Patients

Gender Differences in Knowledge and Perception of Cardiovascular Disease among Italian Thalassemia Major Patients

New Entity—Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement

Vascular Aging and Damage in Patients with Iron Metabolism Disorders

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