Increased Interleukin‐6 levels in pituitary‐deficient patients are independently related to their carotid intima‐media thickness

Leonsson, M.; Hulthe, Johannes; Johannsson, Gudmundur; Wiklund, O.; Wikstrand, John; Bengtsson, Bengt; Oscarsson, Jan

doi:10.1046/j.1365-2265.2003.01832.x

Cited by 44 publications

(35 citation statements)

References 59 publications

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“…The hypothesis that GHD increases the risk of cardiovascular disease is supported by findings that adult patients with GHD present a series of risk factors, such as adverse lipid profiles (10)(11)(12), increased blood pressure, abnormal body composition (13,14), increased body weight (15,16), increased coagulability (17), and increased markers of inflammation (18). These multiple abnormalities promote the development of an accelerated atherosclerotic disease, as shown by decreased aortic compliance (19) and increased intimamedia thickness (20).…”

Section: Introductionmentioning

confidence: 68%

Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults – a KIMS database analysis

et al. 2006

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Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) and some cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large number of patients over a prolonged period of time. Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serum concentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206 patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, resting blood pressure and body composition were also measured. Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profile demonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and the elevated BMI. The cholesterol concentration, BMI and body composition were significantly adversely affected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeutic effect of GH was essentially uniform across the whole population. GH replacement reduced significantly the mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintained during 2 years. Conclusions: This analysis of a large number of patients confirmed that GHD adults present with an increased cardiovascular risk. The sustained improvement of the adverse lipid profile and body composition suggests that GH replacement therapy may reduce the risk of cardiovascular disease and the premature mortality seen in hypopituitary patients with untreated GHD.European Journal of Endocrinology 155 79-90

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Section: Introductionmentioning

confidence: 68%

Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults – a KIMS database analysis

et al. 2006

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“…In patients with hypopituitarism receiving conventional replacement therapy, but not GH, both serum interleukin-6 and C-reactive protein levels are significantly elevated compared with controls (18,63).…”

Section: Other Cardiovascular Factorsmentioning

confidence: 97%

“…The hypothesis that GHD increases the risk of cardiovascular disease is supported by a series of risk factors common to the adult GHD syndrome, such as adverse lipid profiles (10)(11)(12), increased blood pressure (BP), abnormal body composition (13,14), increased body weight (15,16), increased coagulability (17), and increased markers of inflammation (18), leading to an accelerated atheromatosis.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular risk factors in hypopituitary GH-deficient adults

Verhelst¹,

Abs²

2009

European Journal of Endocrinology

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Design: Data on lipids, body composition, and blood pressure (BP) from all published KIMS papers are summarized and compared with a literature review. Results: KIMS data confirm and extend previous research showing that adults with GH deficiency (GHD) have an adverse cardiovascular risk profile. GHD patients have high levels of dyslipidemia, elevated body mass index, unfavorable waist-to-hip ratio and body composition, and a high risk of hypertension. These abnormalities are likely to explain the increased cardiovascular mortality observed in patients with hypopituitarism. When given GH replacement therapy, an improvement is seen in KIMS as well as earlier studies for lipid profile, body composition, and BP. The added value of the different KIMS papers over previous research is that KIMS involves a much larger number of patients, that lipid concentrations and IGF1 are measured in a single central laboratory, and that the effects of GH replacement therapy can be followed longer than the duration of earlier trials. By the large number of patients, KIMS gives insight into the effects of GH in different patients' subgroups such as elderly patients, patients with idiopathic GHD, patients with craniopharyngioma, patients after irradiation, and so on. In addition, KIMS has made it possible to calculate more exactly the influence of baseline parameters on these cardiovascular risk parameters and their response to GH. Conclusions: Taken together, data from KIMS confirm earlier knowledge about the important benefits of GH replacement therapy, but also on the use of GH in specific subgroups such as isolated GHD, patients above 65 years, and patients after irradiation. No subgroup yet has been identified as not responding well to GH.

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“…In acromegaly chronic elevated IGF levels are harmful, and associated with hypertension, DM, fluid retention and a specific hypertrophic cardiomyopathy characterised by the development of CHF (26). On the other hand, a high activity in the GH-IGF1 axis has some potential protective effects on vascular structures favouring reduced development of atherosclerosis (33)(34)(35). Thus, hypothetically protective and harmful effects of IGF1 on CVD might neutralize each other explaining why we, and others (36) observed no association between IGF levels and the overall incidence of CVD in background populations.…”

Section: Discussionmentioning

confidence: 99%

IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population

Andreassen

Raymond

Kistorp

et al. 2009

European Journal of Endocrinology

110

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Background: IGF1 is believed to influence ageing and development of cardiovascular disease (CVD) through complex mechanisms. Reduced IGF1 levels might be causally associated with conditions accompanying ageing including development of CVD. However, in animal models reduced GH-IGF1 signalling increases lifespan. Reduced IGF1 activity might also be associated with longevity in humans. Objective: The objective was to investigate if plasma IGF1 levels were associated with all cause mortality, and the development of chronic heart failure (CHF) and a major CV event.Patients and design: A population based study of 642 individuals, aged 50-89 years. Development of CHF was evaluated in 576 individuals with normal systolic function assessed by echocardiography and without the history of CHF or myocardial infarction. Development of the first major CV event was evaluated in 504 individuals with normal systolic function and without prevalent CVD. Outcomes were ascertained after 5 years using hospital discharge diagnoses. Results: Adjustment for risk factors IGF1 values in the fourth quartile versus values below the fourth quartile was associated with increased mortality (nZ103), hazard ratio (HR) 1.52 (95% confidence interval (CI) 1.01-2.28; PZ0.044). IGF1 in the fourth quartile was also independently associated with risk of development of CHF (nZ19), HR 5.02 (95% CI 2.00-12.64; PZ0.001) but showed no association with the overall incidence of major CV events (nZ58), HR 1.05 (95% CI 0.59-1.90; PZ0.861). Conclusions: High IGF1 levels were independently associated with increased all cause mortality and risk of development of CHF, whereas no relation with the overall incidence of CVD was observed.

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Increased Interleukin‐6 levels in pituitary‐deficient patients are independently related to their carotid intima‐media thickness

Abstract: IL-6 concentrations were increased in GHD patients compared to controls and independently related to IMT in patients. This finding may help to explain the variance in IMT and the increased vascular morbidity and mortality in hypopituitary patients with GHD.

Cited by 44 publications

References 59 publications

Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults – a KIMS database analysis

Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults – a KIMS database analysis

Cardiovascular risk factors in hypopituitary GH-deficient adults

IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population

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