In the present study, we estimated the prevalence of AMD among people who underwent health examination in Hunan, China and determined the relationship between dietary pattern and the risk of AMD. Among the 43,821 subjects who underwent health examination, 1229 (2.80%) had AMD including 1080 (2.5%) early AMD and 149 (0.034%) late AMD. The prevalence of early AMD was slightly higher in males than in females (2.6% vs. 2.3%). the prevalence of early AMD was increased gradually with age in both sexes. Multivariate logistic regression analysis demonstrated that BMI, salt intake and smoking increased the risk of early AMD, while meat consumption and alcohol drinking decreased the risk of early AMD.
According to the global estimation of the prevalence of AMD [1], early- and late-stage AMD were the most common in European populations, with prevalence of 11.20% and 0.50%; early AMD was rare in Asian populations, with a prevalence of 6.81%. At present, only four studies on the prevalence of AMD had been conducted in China, with the prevalence of early AMD ranging from 1.4–40.4% [9–12]. Of the four studies, two had been conducted 10 years ago [9, 10], two had been conducted among elderly populations in rural areas in Middle [10] and South China [11], one had been conducted among elderly populations in urban areas in East China [12]. These studies covered only limited populations in limited areas of China, with a wide time span. The differences in the aging trends of Chinese populations cannot be ignored. Currently, no report on the prevalence of AMD of the entire Chinese population has been published. Our study on the prevalence of AMD among subjects who underwent health examination may enrich the database of AMD in China.
Age was confirmed to be a risk factor of AMD. And the association between sex and the risk of AMD is under debate. Our data demonstrated that the prevalence of early AMD was significantly lower in females than in males among 43,672 subjects of ≥ 50 years old who underwent health examination. However, in multivariate logistic regression sex was not the risk factor of the early AMD analysis, which was in consistent with the results from many previous studies [1, 13–14].
The association between dietary pattern and diseases has been widely reported. Unhealthy dietary patterns, such as high fat and high red meat dietary patterns, are known to affect the development of AMD among genetic susceptible populations [15]. Healthy dietary patterns, such as Mediterranean dietary pattern [16], may provide antioxidant substances to the body and delay the occurrence of age-related diseases. At present, most studies on the direct influence of dietary pattern on AMD were conducted in European and American countries. Chiu et al. [17] used principal component analysis to analyze the food consumption data collected with the food frequency questionnaire (FFQ) released by the AREDS group and classified the dietary pattern as western and eastern dietary patterns. Through cross-sectional study, they found that the western dietary pattern, which was mainly composed of high-fat milk products, butter or margarine, gravy, processed food, eggs, sweeties, sport drinks, and refined food, increased the risk of AMD (OR = 3.70, 95% CI = 2.31–5.92, p < 0.0001); on the contrary, the eastern dietary pattern, which was mainly composed of vegetables, beans, rice, whole grains, fruits, tomato, vegetables with green leaves, low-fat milk products, fish and seafood, decreased the risk of AMD (OR = 0.38, 95% CI = 0.27–0.54, p < 0.0001). In China, diverse dietary patterns with complex compositions are adopted, and their associations with AMD have not been well studied. In the present study, we used the National Unified Physical Examination Questionnaire to collect dietary and lifestyle data and analyzed their associations with AMD. We found that excessive salt intake (OR = 1.60, 95% CI = 1.53–1.67, p < 0.001) and smoking (OR = 1.13, 95% CI = 1.11–1.18, p = 0.024) increased the risk of early AMD.
High-salt intake has been widely proved to be associated with the risks of many diseases, such as hypertension [18], angiocardiopathy [19], and gastric cancer [20]. According to the 2015 global disease burden study [21], high-salt intake was listed as one of the top ten largest contributors to global disability-adjusted life years. In the Diet, Nutrition, and the Prevention of Chronic Diseases: Report of a Joint WHO/FAO Expert Consultation conducted by World Health Organization (WHO) and Food and Agricultural Organization (FAO), the recommended salt intake for Chinese was lower than 5 g/day. The Chinese Nutrition Society suggested that the salt intake of Chinese should be no more than 6 g/day. Yu et al. [22] reported that the average salt intake of Chinese was 9.6 ± 0.3 g/day. Our data demonstrated that the average salt intake was 8.39 ± 0.68 g/day in subjects without AMD and 9.26 ± 0.56 g/day in those with early AMD. Yang et al. [6] analyzed the salt intake data from Hunan subjects of > 65 years old who underwent health examination and reported an average salt intake of 8.15 ± 1.89 g/day. These data indicate that the salt intake of elderly populations in Hunan, China is much higher than the recommended level, severely affecting the health of the eyes and the body. The high salt intake of people in Hunan is related to their eating habits. This area likes to eat salt-pickled meat, fish, etc. The major source of salt (about 70%) comes from processed food. The salt intake is increased rapidly along with the increased consumption of processed food. In the cell experiment, increased salt intake was reported to be an environmental risk factor of AMD [23]. High-salt intake may induce cellular dysfunctions, such as DNA double-strand break, DNA and protein oxidation, structural and functional impairment of mitochondria, cytoskeleton changes, and apoptotic cell death. It may increase the risk of AMD through inducing oxidative stress of RPE cells. The damage of high-salt intake to the retina varied among individuals. In a study on patients with refractory hypertension, it was reported that high-salt intake thickened the arteriolar wall in the retina [24]. In salt-sensitive rats, high-salt intake led to retina arteriolar spasm and ischemia [25].
Experimental study further proved that the high extracellular permeation pressure induced by high-salt intake stimulated RPE cells to express vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), pLacental growth factor (PlGF), and Heparin-binding epidermal growth factor (HB-EGF) [23,26−27]. The transcription activity of hypoxia-inducible factor-1 (HIF-1) and nuclear factor of activated T cell-5 (NFAT5), which is important in the regulation of VEGF, is also affected by the high-salt permeation pressure [23]. The increased plasma osmotic pressure induced by high-salt intake may stimulate regional inflammation in RPE and production of angiogenic factors, leading to the progression of AMD [27].
It is the first time to confirm that high salt intake increased the risk of AMD in the population study. The subgroup analysis found that high salt intake had statistical effect both in non-CKD group and in CKD group in our study. And we also observed the similar results both in non-DM group and in DM group. In addition, we observed some interesting phenomena. Although interactive analysis showed that there was an interaction between hypertension and salt intake. However, stratified analysis showed that high salt intake may have a greater impact on patients without hypertension (OR = 1.62, 95% CI = 1.45–1.81, p < 0.01). In the no hypertension group, the increased salt intake was associated with the higher risk of early AMD, while the corresponding values were not significant for hypertension person(OR = 1.00, 95% CI = 0.99–1.03, p = 0.083).
In subgroup analysis, our study still showed that high-salt intake had the statistical significance on the prevalence of AMD among no-smokers, before-smokers and current-smokers. Interactive analysis showed that there was no interaction between smoking and salt intake. Therefore, it also confirmed that smoking is an independent risk factor for AMD. Interestingly, in the present study, we found that the meat consumption decreased the risk of early AMD (OR = 0.89, 95% CI = 0.80–0.99, p = 0.037). This result was not in consistent with those from Chiu et al. [19]. They found that the western dietary pattern, which was mainly composed of meat, fat, and butter, increased the risk of AMD, but the relationship between meat and the risk of AMD was not investigated. The ketogenic diet was reported to increase β-hydroxybutyrate (β-HB) level, which may prevent or alleviate symptoms of age-related diseases, exert antiaging effect [28], and prolong the lifespan [29–30]. In mammals, β-HB may down-regulate senescence-associated secretory phenotype (SASP) and retard the senescence of vascular cells [31]. The ketogenic diet may also alleviate symptoms of Alzheimers disease, an age-related neurodegenerative disease [32–33]. The dietary pattern adopted by elderly populations in Hunan, China is high-fat and meat-dominant with limited carbohydrates, which is somewhat like to the characteristics of ketogenic diet. Our observation needs to be validated in a prospective cohort study.
Moreover, it should be noted that the confounding effect of lifestyle factors on the prevalence of AMD cannot be completely excluded. In addition, the subjects who underwent health examination in the present study could not represent general populations, especially those in poverty areas and rural areas with limited access to health examination. The proportion of such subjects was low in our cohort, indicating a sampling bias in the present study. In addition, selection bias could not be avoided due to the inclusion of various examinations, such as fundus examination, fundus photography, OCT, and MSI, for the diagnosis of AMD in the present study, affecting the estimation of the prevalence of AMD. Although these limitations existed, we still observed associations between unhealthy dietary patterns and the risk of early AMD.