This study found that H-type hypertension tended to have more severe retinal vessel abnormalities. Patients with H-type hypertension had smaller retinal arteries and more severe retinal arteriosclerosis.
H-type hypertension was first proposed by a Chinese research team in 2008. It refers to patients with hypertension and HHCY at the same time. H-type hypertension accounts for 75% of total hypertension. They found that HCY is another major risk factor for stroke in addition to hypertension. A meta-analysis had identified potentially relevant researches up to August 1, 2019. The conclusion was that hypertension was closely associated with HCY. According to previous findings, a high level of HCY did harm to systemic vascular endothelial cells [10, 11]. Elsherbiny et al further demonstrated that HHCY can undermine inner and outer blood–retinal barriers. We doubt that H-type hypertension may cause more serious retinal vessel lesions. Our study found that patients with H-type hypertension had a higher grade of retinal arteriosclerosis, and smaller diameter of retinal artery compared with isolated hypertension patients. The changes of retinal arteriosclerosis include thinning and straightening of the retinal artery, which is like copper wire or silver wire. The sclerotic artery can compress the vein at the intersection with the vein, which is called AVN. In severe cases, retinal vessel spasm, stenosis, obstruction, and hemorrhages can occur. In our study, retinal arteriosclerosis grades, CRAE and AVR seemed to be more sensitive compared with the rest of lesions. AVN barely failed to attain statistical significance(P = 0.066). And retinal arteries, instead of veins, showed differences between the two groups. Based on these findings, it’s indicative that a higher level of serum HCY may aggravate retinal vessel abnormalities. Researchers have found H-type hypertension could cause more severe cerebrovascular damage compared with isolated hypertension[13, 14]. Similarly, H-type hypertension may cause more serious damage to the retinal vessels. This is similar with what we observed in the present study.
We further analyzed the risk factors of retinopathy. The ratio of H-type hypertension was significantly higher in retinopathy group. Age, history of diabetes and courses of hypertension also showed significant differences in two types of outcomes. Further analysis demonstrated that although the related risk factors were adjusted, H-type hypertension was still a risk factor of retinopathy. Sottilotta et al found that elevated plasma homocysteine could be an independent risk factor of retinal vascular occlusive disease which is closely related to coronary, cerebral, and peripheral atherosclerotic vascular disease. A previous study also the evaluate the availability of HCY as a biomarker for diabetic retinopathy screening, and the result was that HCY could be a strong candidate. Retinopathy described above was closely related to the damage of the retinal vessels. The pathological changes of the retinal vessels are regarded as the window to observe systemic vascular problems. Hypertension can cause sclerosis of small arteries. Tyagi et al found that HCY is one of the circulating plasma factors that may play a critical role in the development of hypertension[16, 17]. There may be an interaction between HCY and hypertension. The mechanism of damage of HCY to small arteries is not completely clear, but the endothelium damage of small vessels by HCY may be an important one of the reasons.
The impact of HCY on small arteries has attracted more and more attention[18–20]. Retinal vessels are the unique small vessels that can be directly observed throughout the body. We directly measured the diameters to evaluate the changes of retinal vessels. And we found that artery was more likely decreased in H-type hypertension, yet the changes of venules were not obvious. The patients in this study all suffered from hypertension, and the difference of retinal abnormalities were caused by HCY. However, whether HCY damages retinal vessels through the superposition effect of hypertension or directly damages retinal vessels remains controversial[4, 12]. Serum HCY is a sulfur-containing amino acid, which is an important intermediate product produced during the metabolism of methionine and cysteine. It has three metabolic pathways. Abnormalities in any of these three metabolic pathways can lead to increased HCY. One of the metabolic pathways is that HCY is catalyzed by vitamin B6 dependent cystathionine β synthetase. HCY is converted to cysteine and eventually metabolizes in the body to produce H2S in the process. Accumulating evidence indicated that H2S is a physiological vasorelaxant and reduced production of H2S in the vascular tissue leads to hypertension[11, 21, 22]. Besides, HHCY may cause direct toxicity and vascular endothelial injury, which may induce hypertension or aggravating the damage of hypertension to vessels[23–25]. Collectively, HCY also activates certain metalloproteinases which can cause degradation of collagen and elastin leading to vascular hypertrophy[26, 27]. Moreover, the accumulation of HCY leads to increased cellular oxidative stress in which mitochondrial thioredoxin and peroxiredoxin are decreased and NADH oxidase activity is increased. In a word, the mechanism of HCY induced arteriosclerosis mainly includes endothelial cell injury, oxidative stress and vascular remodeling. In conclusion, H-type hypertension patients have more severe vascular injury than isolated hypertension patients.
Our study has several potential limitations. There may be manual errors in measuring the diameter of blood vessels even though we tried to avoid that by taking the average value of repeated measurement. It would be better if we could use a newer and more accurate method to analyze the retinal vessel abnormalities. Secondly, when we analyzed, the small sample limited the statistical power of the model. In the future, we need to increase the sample size and conduct cohort studies to better explain these associations and meet the needs of clinical applications.