Abstract
BackgroundPatients with Addison's disease (AD) in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD). Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa.MethodsIn a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden) matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP) and adiponectin were studied.ResultsAll patients were Caucasian and the majority were women N = 36 (65.5%). Mean (standard deviation; SD) ages of the Swedish and South African patients were 52.9 (13.0) and 52.6 (14.4) years and BMI 25.3 (3.2) and 25.8 (4.1) kg/m2, respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1) versus 24.3 (8.0) mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR) triglycerides (TG) [1.59 (1.1–2.46) versus 0.96 (0.74–1.6) mmol/l; p<0.001], total cholesterol (TC) [6.02(1.50) versus 5.13 (0.87) mmol/l; p<0.001], LDL-C [4.43 (1.44) versus 2.75 (0.80) mmol/l; p<0.001] and median hs-CRP [2.15 (0.93–5.45) versus 0.99 (0.57–2.10) mg/L; p<0.003] and lower HDL-C [0.80 (0.40) versus 1.86 (0.46) mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus.ConclusionsSouth African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors.
Highlights
There is a more than two-fold increase in relative risk of death in Swedish patients with Addison’s disease (AD), compared to the background population, predominantly due to cardiovascular disease (CVD) [1,2], with the greatest number of deaths from ischaemic heart disease followed by cerebrovascular disease [1]
In a diverse population of South African patients with AD, we previously demonstrated that AD patients had a wide range of cardiovascular risk factors including elevated triglycerides, lower high density lipoprotein cholesterol (HDL-C) and elevated high sensitivity C-reactive protein than healthy control subjects [3]
The Swedish and South African patients were well-matched with respect to age and body mass index (BMI) (Table 1)
Summary
There is a more than two-fold increase in relative risk of death in Swedish patients with Addison’s disease (AD), compared to the background population, predominantly due to cardiovascular disease (CVD) [1,2], with the greatest number of deaths from ischaemic heart disease followed by cerebrovascular disease [1]. In a diverse population of South African patients with AD, we previously demonstrated that AD patients had a wide range of cardiovascular risk factors including elevated triglycerides, lower high density lipoprotein cholesterol (HDL-C) and elevated high sensitivity C-reactive protein (hs-CRP) than healthy control subjects [3]. AD per se may have contributed to the excess mortality, inadequate or supra-physiological glucocorticoid (GC) replacement therapy may have conferred adverse effects on CVD risk factors [4]. Glucocorticoid (GC) excess has an important impact on cardiovascular risk factors [4]. In a large study of patients with hypopituitarism, a total daily replacement dose of hydrocortisone of $20 mg was associated with an increase in CVD risk factors, as evidenced by increased waist circumference, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) [6].
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