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; β = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; β = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; β = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; β = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; β = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; β = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; β = 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; β = −0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = −0.47, p = 0.01; β = −0.005, p ≤0.01) as well as with diuretics treatment (β = −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.

中文翻译：

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与心血管风险相似的非肢端肥大症研究参与者相比，肢端肥大症患者的脉搏波速度降低

客观的

据报道，肢端肥大症患者的动脉僵硬度增加，这可能导致该人群中频繁出现心血管并发症。GH和IGF-1的慢性过量可能通过不同的机制导致动脉硬化，包括高血压、糖耐量受损和血脂异常，然而，尚不清楚GH/IGF-1轴的激活是否会影响动脉硬化而独立于心血管风险因素。这项前瞻性病例对照研究的目的是比较具有相似心血管风险的肢端肥大症组与非肢端肥大症组用脉搏波速度 (PWV) 评估的动脉僵硬度。

设计

这项前瞻性病例对照研究包括 27 名活动性肢端肥大症患者，他们接受了临床、生理、生化参数的评估以及压平眼压计评估 PWV。我们使用“俄罗斯联邦不同地区心血管疾病流行病学”研究数据库（n  = 522）建立了一个心血管风险相似的非肢端肥大症对照组（n = 54)。除了测量血清 GH 和 IGF-1 水平外，非肢端肥大症对照参与者接受了与肢端肥大症患者相同的评估。我们将肢端肥大症患者的 PWV 与一般非肢端肥大症人群及其亚群进行比较，并与肢端肥大症患者的心血管危险因素相匹配。我们还使用校正年龄和性别的相关性和回归分析研究了肢端肥大症和非肢端肥大症组中 PWV 与临床、生理和生化参数的关联。

结果

与未匹配的非肢端肥大症对照组 (7.50 (6.70–8.57) m/s, p  = 0.01) 和心血管匹配的非肢端肥大症对照组相比，肢端肥大症患者的 PWV (6.70 (5.75–7.65) m/s) 较低风险因素 (7.45 (6.73–8.60), p  < 0.01)。在非肢端肥大症对照组中，PWV 与 BMI (ρ = 0.40, p  < 0.01; β = 0.09, p  < 0.01)、肥胖 ( r  = 0.46, p  < 0.01; β = 1.36, p < 0.01)、收缩压相关压力 (ρ = 0.60, p  < 0.01; β = 0.05, p  < 0.01), 舒张压 (ρ = 0.62, p  < 0.01; β = 0.07, p  < 0.01), 甘油三酯 (ρ = 0.55, p < 0.01; β = 0.58, p  = 0.04)、葡萄糖 (ρ = 0.54, p < 0.01; β = 0.70, p < 0.01) 和糖尿病 ( r  = 0.40, p < 0.01; β = 1.10, p  = 0.03)，而在肢端肥大症中组 PWV 与以 mcg/ml 表示的 IGF-1 相关（ρ = -0.49，p  ≤0.01；β = -0.002，p  ≤0.01）和正常上限的百分比（ρ = -0.47，p  = 0.01；β = -0.005，p ≤0.01）以及利尿剂治疗（β = -1.17，p  = 0.03）。

结论

与心血管风险相似的非肢端肥大症对照参与者相比，肢端肥大症患者的 PWV 降低。未来的研究需要探索 GH/IGF-1 轴在调节动脉壁特性中的作用以及 PWV 作为肢端肥大症心血管并发症预后标志物的可靠性。