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

Aims: As 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. Methods: A 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. Results: Among 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. Conclusions: Reduced 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.