Cannavo Salvatore, Almoto Barbara, Cavalli Giovanni, Squadrito Stefano, Romanello Giovanni, Vigo Maria Teresa, Fiumara Francesco, Benvenga Salvatore, Trimarchi Francesco
Sezione di Endocrinologia, Pad. H, piano 4 Azienda Ospedaliera Universitaria Policlinico G. Martino, Via Consolare Valeria 1, 98125 Messina, Italy.
J Clin Endocrinol Metab. 2006 Oct;91(10):3766-72. doi: 10.1210/jc.2005-2857. Epub 2006 Jul 11.
Coronary atherosclerosis in acromegaly was not extensively investigated in the literature until now. At autopsy, it was demonstrated in about 20% of patients with long-lasting disease, and myocardial infarction was reported as cause of death in a quarter of acromegalics.
The objective of the study was to evaluate coronary atherosclerosis in a cohort of acromegalics with controlled or uncontrolled disease.
Coronary risk was evaluated by the Framingham algorithm, according to the Framingham score (FS). Patients were stratified into low (<6%), intermediate (6-20%), and high (>20%) midterm risk. Coronary calcium deposits were detected by multidetector computed tomography and measured by the Agatston algorithm. Coronary artery calcium [Agatston score (AS)] was quantified at the level of left main artery, left anterior descendent artery, left circumflex artery, right coronary artery, and posterior descendent artery. Total AS values in healthy persons are less than 50 (aged < 60 yr) and less than 300 (age > or = 60 yr).
Thirty-nine patients (12 males and 27 females, aged 53.0 +/- 2.1 yr) were evaluated. In each patient, the mean of at least four determinations of serum IGF-I, assayed during the last 2 yr before study, was normalized for the age-matched normal range, and the result was presented as sd value (IGF-I sd). On the basis of serum IGF-I sd, acromegaly was considered controlled (< or =1.9 sd; n = 24) or uncontrolled (> or = 2.0 sd; n = 15).
The FS was intermediate in 12 and high in two acromegalics. Overall, the FS was not correlated with serum GH values and IGF-I sd. Mean FS was not significantly different between patients with controlled and uncontrolled acromegaly. Total AS was increased in nine patients, most frequently in left anterior descendent, left circumflex, and left main arteries. In these nine patients, mean AS was similar in individuals with controlled and those with uncontrolled acromegaly, and the rate of 17% patients with controlled disease having increased AS was not statistically different from the rate of 33% uncontrolled acromegalics. Total AS was increased in six of 12 males and in three of 27 females (chi(2) 7.1, P < 0.01). Overall, total AS correlated with FS (r(2) = 0.4, P < 0.0002) but not age, body mass index, disease duration, indexed left ventricular mass, serum cholesterol, triglycerides, GH, or IGF-I levels. Increased AS was more frequently observed in acromegalics with diabetes mellitus (chi(2) = 5.2, P < 0.05) or hypertension (chi(2) = 9.8, P < 0.002) but not in smokers (chi(2) = 1.34, P = NS). Seven of nine patients with coronary calcium deposits had a FS greater than 6%. In six of 13 patients with FS greater than 6%, multidetector computed tomography did not demonstrate coronary calcifications.
In our study, the integrated evaluation of FS and AS showed that 41% of acromegalics are at risk for coronary atherosclerosis and that coronary calcifications were evident in about half of them despite the fact that myocardial infarction was not more frequent in acromegalic patients than the general population. Moreover, the control of acromegaly did not influence significantly the extent of coronary atherosclerosis.
迄今为止,文献中对肢端肥大症患者的冠状动脉粥样硬化研究并不广泛。尸检发现,约20%的长期患病患者存在冠状动脉粥样硬化,且四分之一的肢端肥大症患者死因是心肌梗死。
本研究旨在评估一组疾病得到控制或未得到控制的肢端肥大症患者的冠状动脉粥样硬化情况。
根据Framingham评分(FS),采用Framingham算法评估冠状动脉风险。患者被分为低中期风险(<6%)、中中期风险(6 - 20%)和高中期风险(>20%)。通过多排螺旋计算机断层扫描检测冠状动脉钙化,并采用阿加斯顿算法进行测量。在左主干动脉、左前降支动脉、左旋支动脉、右冠状动脉和后降支动脉水平对冠状动脉钙化[阿加斯顿评分(AS)]进行量化。健康人的总AS值小于50(年龄<60岁)和小于300(年龄≥60岁)。
对39例患者(12例男性和27例女性,年龄53.0±2.1岁)进行了评估。在每位患者中,将研究前最后2年期间至少4次测定的血清IGF - I平均值根据年龄匹配的正常范围进行标准化,并将结果表示为标准差(IGF - I sd)值。根据血清IGF - I sd,肢端肥大症被认为得到控制(≤1.9 sd;n = 24)或未得到控制(≥2.0 sd;n = 15)。
12例肢端肥大症患者的FS为中风险,2例为高风险。总体而言,FS与血清GH值和IGF - I sd无关。疾病得到控制和未得到控制的肢端肥大症患者的平均FS无显著差异。9例患者的总AS升高,最常见于左前降支、左旋支和左主干动脉。在这9例患者中,疾病得到控制和未得到控制的患者的平均AS相似,疾病得到控制的患者中AS升高的比例为17%,与未得到控制的肢端肥大症患者中33%的比例无统计学差异。12例男性中有6例总AS升高,27例女性中有3例总AS升高(χ² = 7.1,P < 0.01)。总体而言,总AS与FS相关(r² = 0.4,P < 0.0002),但与年龄、体重指数、病程、左心室质量指数、血清胆固醇、甘油三酯、GH或IGF - I水平无关。在患有糖尿病(χ² = 5.2,P < 0.05)或高血压(χ² = 9.8,P < 0.002)的肢端肥大症患者中更常观察到AS升高,但在吸烟者中未观察到(χ² = 1.34,P =无显著性差异)。9例有冠状动脉钙化的患者中有7例FS大于6%。在FS大于6%的13例患者中有6例,多排螺旋计算机断层扫描未显示冠状动脉钙化。
在我们的研究中,FS和AS的综合评估显示,41%的肢端肥大症患者有冠状动脉粥样硬化风险,尽管肢端肥大症患者中心肌梗死并不比普通人群更常见,但约一半患者有明显的冠状动脉钙化。此外,肢端肥大症的控制对冠状动脉粥样硬化的程度没有显著影响。