Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum.
Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum.
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DOI：
10.3390/jcm11092588
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发表时间：
2022-05-05
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
弹性假性黄瘤（PXE; OMIM 264800）是一种常染色体隐性代谢疾病，以皮肤、布鲁氏膜和脉管系统进行性钙化为特征。PXE的钙化是由ABCC6缺乏引起的循环焦磷酸盐（PPi）水平低引起的。在这项研究中，我们使用了107例PXE患者的队列来确定血浆PPi、冠状动脉钙化（CAC）、下肢动脉钙化（LLAC）和疾病严重程度之间的病理生理关系。总的来说，我们的数据显示PXE患者的血浆PPi与对照组相比存在缺陷。值得注意的是，受影响的女性PPi水平高于男性，但LLAC水平较低。PXE患者的年龄与PPi有很强的相关性（r = 0.423, p < 0.0001），而对照组无相关性（r = 0.059, p = 0.828）。PPi与CAC呈弱相关（r = 0.266, p < 0.02）；然而，与LLAC （r = 0.068, p = 0.518）或严重程度评分（r = 0.077, p = 0.429）无统计学意义相关。令人惊讶的是，我们发现血浆碱性磷酸酶活性与PPi之间没有显著相关性（r = 0.113, p = 0.252）， 10年心血管风险评分与所有其他变量之间也没有显著相关性。多因素分析证实LLAC和CAC与年龄密切相关，而与PPi无关。我们的数据显示，动脉钙化与循环PPi水平只有微弱的联系，而时间（即年龄）似乎是PXE疾病严重程度和钙化的主要决定因素。这些数据对于更好地了解这种疾病的自然史，对患者的随访和管理以及未来临床试验的设计都很重要。我们的研究结果还表明，PPi不是评估疾病严重程度和进展的良好生物标志物。
Pseudoxanthoma elasticum (PXE; OMIM 264800) is an autosomal recessive metabolic disorder characterized by progressive calcification in the skin, the Bruch’s membrane, and the vasculature. Calcification in PXE results from a low level of circulating pyrophosphate (PPi) caused by ABCC6 deficiency. In this study, we used a cohort of 107 PXE patients to determine the pathophysiological relationship between plasma PPi, coronary calcification (CAC), lower limbs arterial calcification (LLAC), and disease severity. Overall, our data showed a deficit in plasma PPi in PXE patients compared to controls. Remarkably, affected females showed higher PPi levels than males, but a lower LLAC. There was a strong correlation between age and PPi in PXE patients (r = 0.423, p < 0.0001) but not in controls (r = 0.059, p = 0.828). A weak correlation was found between PPi and CAC (r = 0.266, p < 0.02); however, there was no statistically significant connection with LLAC (r = 0.068, p = 0.518) or a severity score (r = 0.077, p = 0.429). Surprisingly, we found no significant correlation between plasma alkaline phosphatase activity and PPi (r = 0.113, p = 0.252) or between a 10-year cardiovascular risk score and all other variables. Multivariate analysis confirmed that LLAC and CAC were strongly dependent on age, but not on PPi. Our data showed that arterial calcification is only weakly linked to circulating PPi levels and that time (i.e., age) appears to be the major determinant of disease severity and calcification in PXE. These data are important to better understand the natural history of this disease but also for the follow-up and management of patients, and the design of future clinical trials. Our results also show that PPi is not a good biomarker for the evaluation of disease severity and progression.
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DOI：
10.1073/pnas.1319582110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Jansen, Robert S.;Kucukosmanoglu, Asli;van de Wetering, Koen
通讯作者：
van de Wetering, Koen
影响因子：
11.1
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动脉钙化对弹性假黄瘤周围动脉疾病的贡献。
影响因子：
3.7
作者：
Leftheriotis G;Kauffenstein G;Hamel JF;Abraham P;Le Saux O;Willoteaux S;Henrion D;Martin L
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Martin L
使用ATP硫酶方法的儿童中血浆焦磷酸血浆水平的参考范围。
DOI：
10.1210/clinem/dgab615
发表时间：
2022-01-01
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
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作者：
Bernhard E;Nitschke Y;Khursigara G;Sabbagh Y;Wang Y;Rutsch F
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Rutsch F
DOI：
10.1016/0735-1097(90)90282-t
发表时间：
1990-03-15
影响因子：
24
作者：
AGATSTON, AS;JANOWITZ, WR;DETRANO, R
通讯作者：
DETRANO, R