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      Dual-release hydrocortisone vs conventional glucocorticoids in adrenal insufficiency

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          Abstract

          Background

          Dual-release hydrocortisone (DR-HC) improves metabolism in patients with adrenal insufficiency. The aims of this study were to compare the cardiovascular and metabolic effects of conventional glucocorticoids (GCs) vs. DR-HC and of high vs. low doses of GCs, after 48 months of observation.

          Methods

          We selected 27 patients on hydrocortisone (mean dose 17.5 ± 4.2 mg/day) and 20 patients on cortisone acetate (mean dose 37.5 ± 12.1 mg/day) who maintained this treatment (group A) and 53 patients switched to DR-HC (mean dose 22 ± 4.8 mg/day) (group B). At baseline and after 48 months, clinical and metabolic parameters and Framingham Risk Score (FRS) were obtained.

          Results

          After 48 months, patients in group A had a significant increase from baseline in BMI ( P < 0.001), waist circumference ( P = 0.001), systolic blood pressure ( P = 0.001), LDL cholesterol ( P = 0.018), HbA1c ( P = 0.020) and FRS ( P = 0.002). By contrast, patients in group B had a significant decrease in BMI ( P = 0.002), waist circumference ( P = 0.015), diastolic blood pressure ( P = 0.031), total ( P = 0.006) and LDL cholesterol ( P = 0.005), HbA1c ( P < 0.001) and FRS ( P = 0.015) compared to baseline. No significant differences between high and low doses of both conventional GCs and DR-HC were observed.

          Conclusions

          DR-HC is associated with an improvement of metabolic parameters and cardiovascular risk compared to conventional GCs, which are associated with a worsening of these parameters, regardless of the dose used.

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          Most cited references27

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          General cardiovascular risk profile for use in primary care: the Framingham Heart Study.

          Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions ("general CVD" algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P<0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non-laboratory-based predictors. A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care.
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            The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56).

            A definitive model for predicting absolute risk of coronary heart disease (CHD) in male and female people with Type II diabetes is not yet available. This paper provides an equation for estimating the risk of new CHD events in people with Type II diabetes, based on data from 4540 U.K. Prospective Diabetes Study male and female patients. Unlike previously published risk equations, the model is diabetes-specific and incorporates glycaemia, systolic blood pressure and lipid levels as risk factors, in addition to age, sex, ethnic group, smoking status and time since diagnosis of diabetes. All variables included in the final model were statistically significant (P<0.001, except smoking for which P=0.0013) in likelihood ratio testing. This model provides the estimates of CHD risk required by current guidelines for the primary prevention of CHD in Type II diabetes.
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              Glucocorticoids and cardiovascular disease.

              Chronic excessive activation of glucocorticoid receptors induces obesity, insulin resistance, glucose intolerance, dyslipidaemia and hypertension. Subtle abnormalities of the hypothalamic-pituitary-adrenal axis and/or of tissue sensitivity to glucocorticoids are also associated with these cardiovascular risk factors in patients with the metabolic syndrome. Furthermore, glucocorticoids have direct effects on the heart and blood vessels, mediated by both glucocorticoid and mineralocorticoid receptors and modified by local metabolism of glucocorticoids by the 11beta-hydroxysteroid dehydrogenase enzymes. These effects influence vascular function, atherogenesis and vascular remodelling following intra-vascular injury or ischaemia. This article reviews the systemic and cardiovascular effects of glucocorticoids, and the evidence that glucocorticoids not only promote the incidence and progression of atherogenesis but also modify the recovery from occlusive vascular events and intravascular injury. The conclusion is that manipulation of glucocorticoid action within metabolic and cardiovascular tissues may provide novel therapeutic avenues to combat cardiovascular disease.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                July 2019
                04 June 2019
                : 8
                : 7
                : 853-862
                Affiliations
                [1 ]Dipartimento di Promozione della Salute , Materno – Infantile, Medicina Interna e Specialistica di Eccellenza ‘G. D’Alessandro’ (PROMISE), Sezione di Malattie Endocrine, del Ricambio e della Nutrizione, Università di Palermo, Palermo, Italy
                Author notes
                Correspondence should be addressed to C Giordano: carla.giordano@ 123456unipa.it
                Article
                EC-19-0176
                10.1530/EC-19-0176
                6599082
                31252397
                9acccbf3-85ef-424c-940a-478bfd1bdc11
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 13 May 2019
                : 04 June 2019
                Categories
                Research

                dual-release hydrocortisone,cardiovascular risk,diabetes mellitus,adrenal insufficiency,conventional glucocorticoids

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