Cardiovascular remodeling in active and controlled acromegaly: association with sleep-disordered breathing.

PURPOSE: We hypothesized that an unfavorable cardiovascular profile in acromegaly is associated with sleep-disordered breathing (SDB), while acromegaly control improves both respiratory sleep characteristics and the cardiovascular profile. METHODS: The patients underwent the assessment of breathing during sleep and cardiovascular profile assessment at the start of the study including arterial stiffness, blood pressure, echocardiography, nocturnal heart rate variability (HRV). The assessment was repeated in patients with acromegaly at 1 year after transsphenoidal adenectomy (TSA). RESULTS: A total of 47 patients with acromegaly and 55 control subjects were enrolled. At one year after TSA, 22 patients with acromegaly were reassessed. Multiple linear regression analysis with adjustment for age, sex and body mass index (BMI) showed the associations of insulin growth-like factor 1 (IGF-1) with obstructive apnea index (OAI: ß=0.035/h, p<0.001), but not with cardiovascular parameters, in patients with acromegaly. The analysis of combined acromegaly and control dataset with adjustment for age, sex and BMI showed the association the presence of acromegaly with diastolic blood pressure (DBP; ß=17.99 mmHg, p<0.001), ejection fraction (EF; ß=6.23%, p=0.009), left heart remodeling (left ventricle posterior wall: ß=0.81 mm, p=0.045) and the association of the presence of SDB (apnea-hypopnea index≥15/h) with left ventricular function (EF: -4.12%, p=0.040; end systolic volume: 10.12 ml, p=0.004). Control of acromegaly was accompanied by the decrease in OAI (5.9 [0.8, 14.5]/h and 1.7 [0.2, 5.1]/h, p=0.004) and nocturnal heart rate (66.1 [59.2, 69.8] bpm and 61.7 [54.0, 67.2] bpm, p=0.025) and by the increase in blood pressure (DBP: 78.0 [70.3, 86.0] mm Hg and 80.0 [80.0, 90.0] mm Hg, p=0.012). CONCLUSION: The comorbidities of acromegaly, including sleep-disordered breathing, appear to have a long-term effect on cardiovascular remodeling in active acromegaly. Future studies should investigate the applicability of the treatment of SDB for the reduction of cardiovascular risk in acromegaly.

Pulse wave velocity is decreased in acromegaly compared to non-acromegaly study participants with similar cardiovascular risk profile.

OBJECTIVE: Acromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile. DESIGN: This prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used "The epidemiology of cardiovascular disease in different regions of the Russian Federation" study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex. RESULTS: Acromegaly patients had lower PWV (6.70 (5.75-7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70-8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73-8.60), p < 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p < 0.01; ß = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; ß = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; ß = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; ß = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; ß = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; ß = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; ß = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = -0.49, p ≤0.01; ß = -0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = -0.47, p = 0.01; ß = -0.005, p ≤0.01) as well as with diuretics treatment (ß = -1.17, p = 0.03). CONCLUSIONS: PWV is decreased in acromegaly patients compared to non-acromegaly control participants with similar cardiovascular risk profile. Future studies need to explore the role of GH/IGF-1 axis in the regulation of arterial wall properties and the reliability of PWV as a prognostic marker of cardiovascular complications in acromegaly.

Functional properties of bone marrow derived multipotent mesenchymal stromal cells are altered in heart failure patients, and could be corrected by adjustment of expansion strategies.

BACKGROUND: Bone marrow multipotent mesenchymal stromal cells (BM-MMSC) considered as a prospective substrate for cell therapy applications, however adult stem cells could be affected by donor-specific factors: age, gender, medical history. Our aim was to investigate how HF affects the functional properties of BM-MMSC. MATERIALS AND METHODS: BM-MMSC from 10 healthy donors (HD), and 16 donors with chronic HF were evaluated for proliferative activity, ability to differentiate, replicative senescence, expression of genes that affect regeneration and fibrosis. The effect of culturing conditions on efficiency of BM-MMSC expansion was determined. RESULTS: HF-derived BM-MMSC demonstrated early decrease of proliferative activity and upregulation of genes that control both, regeneration and fibrosis: Tgf-ß pathway, synthesis of ECM, remodeling enzymes, adhesion molecules. We assume that these effects were related to increase of frequency of myofibroblast-like CD146+/SMAα+ CFU-F in HF samples; (ii) low seeding density and hypoxia resulted in predominant purification and expansion of CD146+/SMAα- CFU-Fs. (iii) the activity of NPs system was downregulated in HF BM-MMSC; CONCLUSIONS: downregulation of NP signaling in combination with upregulation of Tgf-ß pathway in BM-MMSC would result in pro-fibrotic phenotype and make these cells non-effective for therapeutic applications; the corrections in culturing strategy resulted in 2(3)-2(7) increase of expansion efficiency.