DataSheet_1_Reduced serum calcium is associated with a higher risk of retinopathy in non-diabetic individuals: The Chinese Multi-provincial Cohort Study.docx

AimsAs a common micro-vascular disease, retinopathy can also present in non-diabetic individuals and increase the risk of clinical cardiovascular disease. Understanding the relationship between serum calcium and retinopathy would contribute to etiological study and disease prevention.
MethodsA total of 1836 participants (aged 55–84 years and diabetes-free) from the Chinese Multi-Provincial Cohort Study-Beijing Project in 2012 were included for analyzing the relation between serum calcium level and retinopathy prevalence. Of these, 1407 non-diabetic participants with data on serum calcium in both the 2007 and 2012 surveys were included for analyzing the association of five-year changes in serum calcium with retinopathy risk. The retinopathy was determined from retinal images by ophthalmologists and a computer-aided system using convolutional neural network (CNN). The association between serum calcium and retinopathy risk was assessed by multivariate logistic regression.
ResultsAmong the 1836 participants (male, 42.5%), 330 (18.0%) had retinopathy determined by CNN. After multivariate adjustment, the odds ratio (OR) comparing the lowest quartiles (serum calcium < 2.38 mmol/L) to the highest quartiles (serum calcium ≥ 2.50 mmol/L) for the prevalence of retinopathy determined by CNN was 1.58 (95% confidence interval [CI]: 1.10 – 2.27). The findings were consistent with the result discerned by ophthalmologists, and either by CNN or ophthalmologists. These relationships are preserved even in those without metabolic risk factors, including hypertension, high hemoglobin A1c, high fasting blood glucose, or high low-density lipoprotein cholesterol. Over 5 years, participants with the sustainably low levels of serum calcium (OR: 1.58; 95%CI: 1.05 – 2.39) and those who experienced a decrease in serum calcium (OR: 1.56; 95%CI: 1.04 – 2.35) had an increased risk of retinopathy than those with the sustainably high level of serum calcium.
ConclusionsReduced serum calcium was independently associated with an increased risk of retinopathy in non-diabetic individuals. Moreover, reduction of serum calcium could further increase the risk of retinopathy even in the absence of hypertension, high glucose, or high cholesterol. This study suggested that maintaining a high level of serum calcium may be recommended for reducing the growing burden of retinopathy. Further large prospective studies will allow more detailed information.

研究目的：视网膜病变作为一类常见微血管疾病，亦可累及非糖尿病人群，且会提升临床心血管疾病的发病风险。阐明血清钙与视网膜病变间的关联，可为该疾病的病因学探索与预防干预提供理论依据。
研究方法：本研究纳入2012年中国多省份队列研究-北京项目中的1836名参与者（年龄55~84岁，无糖尿病病史），用于分析血清钙水平与视网膜病变患病率之间的关联。其中，在2007年与2012年两项调查中均具备血清钙检测数据的1407名非糖尿病参与者，被用于分析血清钙5年变化量与视网膜病变发病风险的相关性。视网膜病变的诊断由眼科医师联合采用卷积神经网络（convolutional neural network, CNN）的计算机辅助系统对眼底影像进行判读完成。采用多因素logistic回归模型评估血清钙与视网膜病变风险之间的关联。
研究结果：在1836名参与者中（男性占比42.5%），共330例（18.0%）经卷积神经网络判读确诊为视网膜病变。经多因素校正后，以血清钙最高四分位组（血清钙≥2.50 mmol/L）为参照，最低四分位组（血清钙<2.38 mmol/L）的视网膜病变患病率比值比（odds ratio, OR）为1.58（95%置信区间[CI]：1.10~2.27）。该结果与眼科医师人工判读的结果具有一致性，无论采用卷积神经网络还是眼科医师的诊断标准，所得关联均无显著差异。即便在无代谢危险因素（包括高血压、高糖化血红蛋白A1c、空腹血糖升高或低密度脂蛋白胆固醇升高）的亚组人群中，上述关联依然显著存在。随访5年后，与血清钙持续处于高水平的参与者相比，血清钙持续处于低水平的参与者（OR: 1.58; 95%CI: 1.05~2.39）以及血清钙水平出现下降的参与者（OR: 1.56; 95%CI: 1.04~2.35）的视网膜病变发病风险显著升高。
研究结论：血清钙水平降低与非糖尿病群体的视网膜病变发病风险升高存在独立相关性。此外，即便在无高血压、高血糖或高胆固醇血症的人群中，血清钙水平下降仍可进一步升高视网膜病变的发病风险。本研究提示，维持适宜的高水平血清钙或可有助于减轻视网膜病变的疾病负担。未来需开展更大样本量的前瞻性研究以获取更详尽的相关信息。