Introduction

Hypertension is a prevalent chronic disease worldwide, and its prevalence is expected to increase in the future owing to an aging population and unhealthy lifestyles [1,2]. In the past three decades, the hypertensive population has significantly increased, nearly doubling from 6.5 million to 1.28 billion worldwide among people aged 30-79 years [3]. The age-standardized prevalence rates of hypertension are 32% and 34% for female and male adults, respectively, suggesting that roughly 1 in 3–4 adults is affected [4]. According to the 2023 Korean National Health and Nutrition Examination Survey, hypertension affects 28.6% of adults aged ≥19 years and 63.5% of those aged ≥65 [5]. It is the second most prevalent disease after periodontal disease, according to medical benefit statistics [6]. Despite the high prevalence of hypertension, its control rate, denoting the percentage of people with normal blood pressure in the prevalent population, is notably low. According to the KCDC [5], the control rate is 50.4% among individuals aged ≥19 years. However, it declined to 35.2% among those in their 40s as the prevalence of hypertension significantly increased.

Persistent uncontrolled hypertension can lead to microvascular and macrovascular complications. Hypertensive retinopathy (HTR) is a common disease found in adults with hypertension and is a representative microvascular complication of hypertension [7,8]. Studies conducted since 2000 have reported a high prevalence of HTR in both nondiabetic hypertensive patients, reaching up to 57.1% [9], and hypertensive patients with diabetes mellitus (DM), with rates ranging from 59.3% to 74.4% [7,10,11]. Retinal blood vessels differ from other blood vessels in that they lack sympathetic nerve innervation and are protected by a blood-retinal barrier. Therefore, an increase in blood pressure directly affects the retinal blood vessels. The primary responses to stimulation are arteriolar constriction and stenosis. Prolonged pressure can lead to reduced perfusion due to arteriosclerosis, causing retinal ischemia, vascular remodeling, and arteriovenous nicking. Whether acute or chronic, this sustained pressure accelerates vascular damage, leading to the breakdown of the blood-retinal barrier. This breakdown results in hemorrhage and the exudation of hard lipid exudates. Additionally, increased intracranial pressure compresses the optic nerve papilla and surrounding blood vessels, causing optic nerve papilla ischemia and papilledema, ultimately contributing to vision loss [12]. Although HTR can lead to vision loss, its significance lies in its role as a risk factor for the occurrence and worsening of diabetic retinopathy (DR). DR is one of the most common causes of irreversible visual impairment in working-age individuals [13]. Hypertension-induced damage to the retinal vessels is associated with proliferative changes and the worsening of DR [14]. Notably, the rigorous control of blood pressure to less than 150/85 mmHg slows the progression of DR and reduces the risk of vision loss compared with the control measures [15].

Considering the significant impact and severity of HTR, proactive measures are essential for its prevention and management. The prevention and control strategies to reduce the disease burden are generally categorized into population risk and high-risk strategies, which are often used in combination [16,17]. Population strategies focus on decreasing the overall risk of HTR by preventing the development of hypertension, which is the primary component of the disease. High-risk strategies are aimed at diminishing the risk of retinopathy in hypertensive individuals through the identification of risk factors, individual risk assessment, and the screening and management of those deemed to be at high risk. Population strategies can be applied to local populations who have not yet developed hypertension, while high-risk strategies should be prioritized for those who have been diagnosed with hypertension. However, recent systematic reviews have explored the risk factors for DR [14,18,19], but similar comprehensive reviews for HTR are currently lacking.

Both hypertension and hyperglycemia are significant associated factors for retinal diseases. From epidemiological, morphological, and pathophysiological perspectives, the signs of HTR exhibit striking similarities with those of DR [20]. Hypertension and DM share a reciprocal relationship [21], with hypertension being a risk factor for the development and exacerbation of DR [22]. Additionally, considering that approximately 20% of patients with HTR have comorbid diabetes [23], associated factors for HTR may vary depending on whether a patient has concurrent DM. Therefore, this systematic review aimed to identify associated factors for HTR in patients with hypertension, especially depending on the presence of DM.

Methods

Protocol and registration

The review was conducted in accordance with the JBI Manual for Evidence Synthesis [24] and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [25] (Appendix 1, 2). Prior to this study, the protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration date: October 6, 2023; registration number: CRD42023470124).

PEO and eligibility criteria

The key question guiding this review was “What are the associated factors for retinopathy among patients with hypertension depending on the presence of DM?”. In this context, participants (P) were defined as hypertensive patients aged 18 years or older with a high prevalence of HTR, exposure of interest (E) as associated factors, and outcomes (O) as retinopathy. Factors associated with HTR were limited to those analyzed by multiple logistic regression and multiple linear regression. Cross-sectional, case-controlled and cohort studies; studies published in Korean and English languages; and studies with available original full texts were included in the review. By contrast, abstracts, book chapters, posters, and protocols were also excluded.

Search strategy

The Cochrane Handbook recommends searching both MEDLINE and Embase for high-quality systematic reviews [26]. A comprehensive search was conducted using four international databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), and Web of Science) and three Korean databases (Research Information Sharing Service (RISS), Koreanstudies Information Service System (KISS), and DBpia) from their inception to June 24, 2023. The search terms were categorized into MeSH terms and natural language terms about HTR and its associated or risk factors, and then combined using the Boolean search operator “AND” (Table 1). The MeSH terms were derived from PubMed, while the natural language terms were identified from systematic reviews of DR [14,18,27] and refined with the assistance of a librarian. Appendix 3 presents the detailed search strategies. Gray literature search was limited to domestic literature as it was difficult to find foreign literature.

Study selection

Two groups of paired reviewers jointly screened the literature. Four reviewers assessed study eligibility for the international database, and two reviewers independently assessed study eligibility for the Korean database. In cases of disagreements among the reviewers, a third meta-analysis expert was consulted. Endnote, a bibliographic export program, was used to manage the bibliographic information of all articles, and duplicate articles were excluded. Following the removal of duplicates, titles and abstracts were reviewed to identify records that met the inclusion criteria, and ineligible studies were excluded. The remaining articles underwent a thorough eligibility check through a full-text review, and the reasons for exclusion were described.

Data extraction

Six researchers independently extracted the data from the articles, and the first and second authors confirmed the final review data. The first author, year, country of publication, study design, participant characteristics (sample size, mean or median age, diagnosis criteria for hypertension, and inclusion or exclusion of diabetes), diagnostic criteria for hypertension, independent variables, dependent variables, and associated factors (group category, adjusted odds ratio (OR) and its 95% confidence interval (CI) based on the multiple linear regression analysis) identified in the multiple regression analysis were extracted using Excel. The associated factors for HTR were summarized by listing the data extracted from each article and classified according to the presence of DM of the participants.

Methodological quality assessment

Six researchers independently evaluated the methodological quality of the selected studies using a checklist developed by the Joanna Briggs Institute (JBI). The JBI critical appraisal checklist for analytical cross-sectional studies [28] was utilized as the selected studies followed a cross-sectional design. The scoring criteria for assessment were categorized as “Yes,” “No,” “Unclear,” and “Not applicable.” A “Yes” response indicated that the methodological quality assessment criteria set by JBI were satisfied. The JBI quality assessment tool does not provide quantitative criteria for evaluating the quality of articles but rather assesses the appropriateness of the assessment questions. Six researchers independently evaluated the quality of the articles, and a consensus was reached through thorough discussion.

Ethical considerations

The study was conducted after receiving approval for exempt review from the Institutional Review Board (IRB) of Pusan National University (No.: 2023_121_HR).

Results

Search results

1. Study selection

A total of 19,094 potential records were retrieved from seven databases: PubMed (n=3,414), Embase (n=12,128), CINAHL (n=2,602), Web of Science (n=947), RISS (n=3), KISS (n=0), and DBpia (n=0). After removing 5,180 duplicates, 838 articles not published in Korean or English, and 4,157 studies with ineligible study designs, the titles and abstracts of the remaining 8,919 studies were screened. Sixty studies that met the inclusion criteria were selected for full-text review; however, the full texts of 15 studies were not available. An additional 34 studies were excluded as 10 of them did not investigate the associated factors for HTR and 23 included healthy individuals. A total of 11 studies were included in the final analysis (Appendix 4). Among the 11 studies, three included patients with DM, while eight excluded them. The entire search process is illustrated in the PRISMA flowchart (Figure 1).

2. Methodological quality assessment

Six studies met all eight criteria (72.7%) (Table 2). Two studies [29,30] provided limited information regarding the participants and settings. One study did not identify the confounding factors and thus failed to address them [31]. None of the studies were excluded based on methodological quality.

3. Characteristics of included studies

Table 3 presents a summary of the characteristics of the 11 included studies. A total of 21,954 participants from seven countries were included in this systematic review. Among the 11 studies, the sample sizes ranged from 73 [32] to 12,966 [23]. The mean age of the participants, where specified, ranged from 45.8±14.3 [33] to 63.9±7.3 years [23]. All included studies had a cross-sectional design. Three studies were conducted in the Republic of Türkiye [29,30,32], three studies in China [23,34,35], one study in Uganda [36], one study in the Democratic Republic of the Congo [31], one study in Tanzania [33], one study in Nepal [37], and one study in the United States [38]. All included studies regardless of the presence of DM were published after 2005, with the majority published within the last 10 years.

Factors associated with HTR

The identified factors associated with HTR included age, sex, lifestyle, blood pressure, changes in the heart and blood vessels, impaired kidney function, medications, and serum glucose and lipid levels (Table 3, 4). Among the 11 studies, three included patients with DM [23,31,34], while eight excluded them (Table 4). The common associated factors identified in both studies were age and impaired kidney function.

Some differences emerged in the findings based on the included participants. Among the three studies that identified age as an associated factor, one study including patients with hypertension with DM [31] reported a 77% lower association in those aged >50 years, while two studies excluding patients with hypertension with DM reported that older age posed a stronger association [30,36]. In terms of lifestyle factors, smoking was identified as a protective factor in a previous study that included participants with DM [31], while alcohol intake was identified as an associated factor in a study that excluded participants with DM [33].

Impaired kidney function was the most frequently reported associated factor in the included studies. Among the 11 studies, 10 examined various renal function indicators. Among these, the presence of chronic kidney disease (CKD) [31,33], hyperuricemia [23], microalbuminuria [30], high creatinine levels [30], urinary albumin-to-creatinine ratio (UACR), and albuminuria [34] were identified as significant associated factors in five studies. Among these factors, creatinine levels had the highest odds ratio at 10.46 (95% confidence interval [CI]: 2.45–44.74, p=.002) [30]. The likelihood of HTR increased significantly with a more severe stage of CKD, with odds ratios of 4.28 in stage 4 (95% CI:1.56–11.74, p=.005) and 8.62 in stage 5 (95% CI:3.56–20.87, p<.001), compared with stage 3 [33]. HTR was also 2.04 times more prevalent in patients with microalbuminuria (95% CI:1.22–3.41, p=.006) [30], 1.57–2.02 times higher in patients with albuminuria [34], and 1.18 times more common in the patients with hyperuricemia (95% CI: 1.05–1.33, p=.004) [23]. A higher grade of HTR was more likely to be associated with grade 3 UACR (β=5.17, p=.012) [23].

Blood pressure was not identified as an associated factor in any of the three studies that included participants with DM, while three studies that excluded participants with DM recognized blood pressure as an associated factor. In a study conducted in Uganda [36], HTR was 3.53 times more likely to occur in patients with a systolic blood pressure (SBP) of ≥140mmHg. In a study conducted in Tanzania, patients with grade I hypertension and patients with grade III hypertension had 2.67 times and 2.51 times higher risk of developing HTR, respectively, than those with normal blood pressure [33]. Karadag et al. [30] specifically examined the association between changes in blood pressure from daytime to nighttime and reported that a reduction of <10% in the mean SBP was as a significant associated factor, with an odds ratio of 2.20. A longer hypertension duration has also been associated with the development of HTR [35,36]. In both studies, a hypertension duration of >5 years was identified as an associated factor.

Four studies reported changes in the heart and blood vessels as associated factors [29,32,35,38]. HTR was more likely to occur in patients with aortic arch calcification, carotid plaques, carotid intima-media thickening, epicardial adipose thickness, and left ventricular hypertrophy (LVH), with odds ratios ranging from 1.674 to 13.13. In a study by Zhang et al. [34], the identification of endothelin-1(ET-1) as a significant associated factor for HTR also highlighted its diagnostic value. The authors suggested that 43.5ng/l can be used as a diagnostic threshold.

Medication, serum glucose, and lipid levels were also identified as associated factors in studies that excluded participants with DM. Among the antihypertensive medications, the association of HTR were 3.05 times higher in patients who used β-blockers, 2.16 times higher in patients who used calcium channel blockers, and 2.91 times higher in patients who used diuretics [36]. Higher serum glucose [29] and lipid levels [32,37] slightly increased the likelihood of developing HTR.

Discussion

A systematic review was conducted to examine the associated factors for HTR, and 11 cross-sectional studies were selected. These studies were categorized into two groups to analyze the factors associated with HTR. Three studies included hypertensive patients with DM, while eight studies only included patients with hypertension without DM.

Impaired kidney function is an associated factor for HTR regardless of the presence of DM [23,30,31,33,34]. Hypertension can either cause or result from CKD and also influence its progression [39]; its severity increases with the declining estimated glomerular filtration rate (eGFR) and advanced stages of CKD [33]. Additionally, DM is a chief associated factor for CKD, and the incidence of CKD is higher in patients with both hypertension and DM than in those with either hypertension or DM alone [40]. Among renal function indicators, CKD [31], UACR [34], albuminuria [34], and uric acid [23] were identified as significant factors in the studies that included individuals with DM, while CKD [33], creatinine levels [30], and microalbuminuria [30] were significantly associated with HTR in studies that excluded individuals with DM. Studies employing predictive models of DR have consistently highlighted abnormal UACR [41], high creatinine levels [42,43], and low eGFR [43] as associated factors for retinopathy, supporting our findings.

This suggests that individuals with hypertension, diabetes, and CKD or those with elevated levels of creatinine, albuminuria, and uric acid should undergo regular eye examinations in addition to periodic renal function assessments. However, due to the cross-sectional nature of the selected studies and variations in the types of renal function indicators and outcome test methods among the studies, it was not possible to determine the differences in renal function indicators based on the presence or absence of DM and identify the most sensitive predictors for HTR. Therefore, further longitudinal studies are warranted.

Among the general characteristics of the participants, age emerged as a factor associated with HTR in 3 of the 11 studies. Studies that involved patients with hypertension without DM demonstrated that older age is a significant associated factor for HTR [30,36]. Conversely, studies involving patients with hypertension with DM revealed that older age is a protective factor against HTR [31]. Previous studies on age and DR have shown that age is a protective factor against DR, with patients with DM aged ≥45 years having a reduced risk of severe fibrovascular proliferation compared with those aged <45 years [44]. Additionally, DR decreased with increasing age [42]. In light of these findings, active screening for retinopathy should be considered in older patients, primarily those with a longer duration of hypertension but without DM. Conversely, screening for retinopathy should begin at a younger age, specifically at the time of DM or hypertension diagnosis in patients with hypertension with DM.

Smoking was investigated in six studies and was shown to lower the risk of HTR in one study that included patients with DM [31]. The relationship between smoking and DR has demonstrated inconsistency, with smoking identified as an associated factor for DR in a study involving individuals with type 1 DM [45] and as a protective factor in some studies involving individuals with type 2 DM [45,46]. In general, smoking is known to reduce retinal blood flow due to the vasoconstrictor effects of nicotine [47] and to decrease blood oxygen-carrying capacity and retinal oxygen delivery by increasing carbon monoxide hemoglobin levels [48]. As the study that identified an association between smoking and HTR [31] was cross-sectional in nature without temporal follow-up, it was difficult to conclude the relationship between smoking and HTR. Further prospective cohort studies are needed to confirm the causality.

Alcohol consumption was investigated in 4 of the 11 studies and was a factor associated with HTR in one study that excluded individuals with DM [33]. This aligns with the results of previous research establishing positive correlations between alcohol consumption, blood pressure, hypertension prevalence, and cardiovascular disease risk [49]. However, this observation does not consider the potential amplification of vascular complications in the presence of comorbid DM, necessitating more stringent blood pressure control [21]. Therefore, additional studies are needed to investigate the effect of alcohol consumption on the incidence of HTR in patients with and without DM, and alcohol abstinence is recommended to prevent HTR.

Among blood pressure values, SBP was investigated in eight studies but was reported as a factor associated with HTR in only one study that excluded individuals with DM [36]. In addition, the duration of hypertension, high BP levels, and non-dipping hypertension (HTN) were identified only in studies that excluded individuals with DM. Additionally, the duration of hypertension was a predictor of HTR in two studies with conflicting results. Higher BP levels [33] and non-dipping HTN [30] have been shown to increase the risk of HTR. Persistently high blood pressure causes changes in the retinal arteries, triggering the occurrence of HTR symptoms including microaneurysms, hemorrhages, exudation of blood and lipids, retinal ischemia, and papilledema [50]. Given this pathophysiology, a robust association exists between the duration of high blood pressure and HTR [35,36]. Generally, a diagnosis of hypertension exceeding 5 years increases the risk of developing retinopathy [36]. However, little is known about the appropriate timing of eye examinations. Therefore, longitudinal studies including people with DM are needed to determine the risk of developing HTR depending on the degree and duration of hypertension, the presence of DM, and the appropriate timing of eye examinations after the diagnosis of hypertension.

Indicators related to lipid metabolism were investigated in studies that excluded individuals with DM, and low-density lipids were identified as a factor associated with HTR in one of two studies and hyperlipidemia in one of three studies. Hyperlipidemia causes increased blood viscosity, atherosclerosis formation, and thickening of the arterial wall, leading to endothelial cell damage and plaque formation. This process results in infarction and ischemic damage to the target organ and is closely associated with heart problems, stroke, and peripheral artery disease [32]. Dyslipidemia can also exacerbate elevated blood pressure, further amplifying the target organ damage throughout the body [37]. These findings underscore the necessity of treating hyperlipidemia to prevent HTR.

Moreover, changes in the cardiovascular parameters such as plasma levels of ET-1, fat thickness of the epicardium, LVH, intima-media thickness of the carotid artery, carotid atherosclerotic plaques, and aortic arch calcification were investigated in two studies. Among these, LVH was associated with a 4.01-fold increase in the odds ratio of HTR in a study that excluded patients with DM [38]. Furthermore, severe cardiac and carotid wall alterations have been observed in participants with severe HTR [38]. Plasma ET-1 levels and fat thickness of the outer cardiac membrane were investigated in studies excluding patients with DM and were shown to be associated factors for HTR [32,35]. Presence of aortic arch calcification was significantly associated with HTR in a study excluding individuals with DM [29]. These findings suggest that HTR can predict other conditions, including cardiovascular diseases, stroke, and CKD [12].

Finally, medication history was identified as a factor associated with HTR. In one study that excluded patients with DM, the association of HTR was higher in patients who used beta-blockers than in those who used diuretics or calcium channel blockers. In another study [38] that excluded patients with DM, medication use was not significantly associated with HTR. Given that newly diagnosed patients with hypertension without antihypertensive treatment have a higher incidence of HTR [32] and that effective blood pressure control reduces the risk of retinopathy [35], additional studies accounting for the adherence and adverse effects of medications are needed.

Nursing interventions and health education should be provided for the prevention and management of HTR in patients with hypertension in the community. Specifically, the Primary Care Chronic Disease Management Program should include screening and management of high-risk groups for hypertensive retinopathy in patients with hypertension. Currently, retinal disease is confirmed through questionnaires in patients with diabetes or hypertension, but eye examinations for patients with hypertension should be included in the screening and evaluation area. Specific guidelines are needed for patient risk group classification so that patients with hypertension can be classified as medium-risk or high-risk groups when they have kidney disease-related characteristics. Accordingly, close management including eye examinations is necessary. Nurses should educate patients with hypertension or diabetes that eye examinations and management should begin from the time diabetes or hypertension is additionally diagnosed. They should also educate that periodic kidney function evaluations are necessary.

The significance of this study lies in its rarity as a systematic review of HTR. While previous systematic reviews of retinopathy predominantly focused on diabetic retinopathy, this study identified the factors associated with HTR based on the adjusted values. Second, this study aimed to report the factors associated with HTR in patients with hypertension with and without DM to identify those who require early screening for HTR based on the concurrence of DM. Third, the procedures of conducting systematic reviews were strictly followed, including PROSPERO registration and adherence to JBI Manual for Evidence Synthesis and PRISMA guidelines. Additionally, a quality assessment was conducted to increase the precision of findings by selectively including studies that performed multiple regression analyses.

Nevertheless, this study has a few limitations that must be addressed. First, the studies included in this review were cross-sectional in nature and had a limitation in establishing a temporal relationship between HTR and associated factors. That is, though impaired kidney function or cardiovascular changes showed significant association with HTR, it is not known which precede. Therefore, further studies should employ longitudinal study designs, such as cohort studies, to establish etiological relationship between HTR and associated factors. Second, the limitation of including only written in English and Korean may have issues with language bias (selection bias), necessitating future studies in diverse languages. Third, the predominantly Turkish and Chinese origin of studies included in this review, with additional studies from the United States, Congo, Uganda, and Nepal, may limit the generalizability of the findings to other cultural contexts. Conducting associated factor studies for HTR in diverse cultures and regions is crucial for drawing generalizable conclusions. Nonetheless, this study is significant in that it provides an opportunity for new research by identifying gaps in existing knowledge, areas of insufficient evidence, and limitations of existing studies. Fourth, although the studies included in this review demonstrated good methodological quality, caution is advised when interpreting the results from the study by Kabedi et al. [31] due to its lower rating concerning confounding factor identification, strategies to address them, and valid and reliable measurements of the outcome variables. Fifth, the caution observed during the comparison of all included studies arises from the heterogeneity in the inclusion criteria, types of variables and measures, and the presentation of results. Additionally, the assessment of most factors, except for age and duration of hypertension, was conducted in only one study. Consequently, a meta-analysis was not performed. Hence, the pooled effect estimate could not be calculated. Finally, adjusted associated factors were extracted from each study, but some studies did not indicate exactly which variables were adjusted. Accordingly, this study presented explanatory variables that were expected to have been adjusted.

Conclusions

In this study, the factors associated with HTR, including older age, male sex, alcohol consumption, duration of hypertension, hyperglycemia, dyslipidemia, microalbuminuria, elevated serum creatinine levels, CKD, and abnormal cardiovascular findings, were identified through a systematic review of patients with hypertension without DM. In studies that included patients with hypertension with DM, younger age, non-smoking status, and impaired kidney function manifested by albuminuria, elevated serum creatinine levels, CKD, and uric acid were identified as associated factors. Regardless of the inclusion of participants with DM, the parameters of impaired kidney function, such as albuminuria, serum creatinine levels, and CKD, have been identified as major associated factors for retinopathy in patients with hypertension. However, considering limited number of evidence and lack of evidence to confirm causality, we recommend further research on renal function and HTR. Based on the findings of this study, community nurses can produce educational materials and provide education to prevent retinopathy in people with high blood pressure or high blood pressure with diabetes. In addition, nurses can recommend periodic retinopathy screening to those with associated factors for hypertensive retinopathy. 

Figure 1.

PRISMA 2020 flowchart of study selection

CINAHL=Cumulative Index to Nursing and Allied Health; DM=diabetes mellitus; HTR=hypertensive retinopathy; RISS= Research Information Sharing Service

References

• 1. Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, et al. Global disparities of hypertension prevalence and control: A systematic analysis of population-based studies from 90 countries. Circulation. 2016;134(6):441–450. https://doi.org/10.1161/CIRCULATIONAHA.115.018912ArticlePubMedPMC
• 2. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nature Reviews Nephrology. 2020;16(4):223–237. https://doi.org/10.1038/s41581-019-0244-2ArticlePubMedPMC
• 3. World Health Organization(WHO). More than 700 million people with untreated hypertension: Number of people living with hypertension has doubled to 1.28 billion since 1990 [Internet]. Geneva: WHO. 2021 [cited 2023 Dec 31]. Available from: https://www.who.int/news/item/25-08-2021-more-than-700-million-people-with-untreated-hypertension
• 4. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants. Lancet. 2021;11:398(10304):957-980. https://www.who.int/news/item/25-08-2021-more-than-700-million-people-with-untreated-hypertension
• 5. Statistics Korea. Trends in the prevalence of hypertension [Internet]. Daejeon: Statistics Korea. 2025 [cited 2025 Mar 16]. Available from: https://kosis.kr/statHtml/statHtml.do?orgId=177&tblId=DT_11702_N105&conn_path=I2
• 6. Kim SM, Kang DT. 2021 Medical Aid Statistics. Wonju: National Health Insurance Service; 2022 October. Report No.: 920015.
• 7. Erden S, Bicakci E. Hypertensive retinopathy: Incidence, risk factors, and comorbidities. Clinical and Experimental Hypertension. 2012;34(6):397–401. https://doi.org/10.3109/10641963.2012.663028ArticlePubMed
• 8. Yıldırım T, Özkan S, Yılmaz ÖÇ, Yavuz B. Increased rate of any retinopathy risk in patients with masked hypertension. Clinical and Experimental Hypertension. 2020;42(6):479–482. https://doi.org/10.1080/10641963.2019.1705320ArticlePubMed
• 9. Wong TY, Klein R, Sharrett AR, Manolio TA, Hubbard LD, Marino EK, et al. The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study. Ophthalmology. 2003;110(4):658–666. https://doi.org/10.1016/S0161-6420(02)01931-0ArticlePubMed
• 10. Kang S, Roh YJ, Moon JI. Hypertensive retinopathy and associated target organ damage in Korean hypertensive patients. Journal of the Korean Ophthalmological Society. 2010;51(9):1231–1236. https://doi.org/10.3341/jkos.2010.51.9.1231Article
• 11. Chen X, Liu L, Liu M, Huang X, Meng Y, She H, et al. Hypertensive retinopathy and the risk of stroke among hypertensive adults in China. Investigative Ophthalmology & Visual Science. 2021;62(9):28. https://doi.org/10.1167/iovs.62.9.28ArticlePubMedPMC
• 12. Dziedziak J, Zaleska-Żmijewska A, Szaflik JP, Cudnoch-Jędrzejewska A. Impact of arterial hypertension on the eye: A review of the pathogenesis, diagnostic methods, and treatment of hypertensive retinopathy. Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2022;28:e935135. https://doi.org/10.12659/MSM.935135ArticlePubMedPMC
• 13. Steinmetz JD, Bourne RRA, Briant PS, Flaxman SR, Tayler HRB, Jonas JB, et al. Causes of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the right to sight: An analysis for the global burden of disease study. The Lancet Global Health. 2021;9(2):e144–e160. https://doi.org/10.1016/S2214-109X(20)30489-7ArticlePubMed
• 14. Song P, Yu J, Chan KY, Theodoratou E, Rudan I. Prevalence, risk factors and burden of diabetic retinopathy in China: A systematic review and meta-analysis. Journal of Global Health. 2018;8(1):010803. https://doi.org/10.7189/jogh.08.010803ArticlePubMedPMC
• 15. UK Prospective Diabetes Study (UKPDS) Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Archives of Ophthalmology. 2004;122(11):1631–1640. https://doi.org/10.1001/archopht.122.11.1631ArticlePubMed
• 16. Hunter E, Kelleher JD. A review of risk concepts and models for predicting the risk of primary stroke. Frontiers in Neuroinformatics. 2022;16:883762. https://doi.org/10.3389/fninf.2022.883762ArticlePubMedPMC
• 17. Rose G. Sick individuals and sick populations. International Journal of Epidemiology. 1985;14(1):32–38. https://doi.org/10.1093/ije/14.1.32ArticlePubMed
• 18. Vivanco-Rojas O, López-Letayf S, Londoño-Angarita V, Magaña-Guerrero FS, Buentello-Volante B, Garfias Y. Risk factors for diabetic retinopathy in Latin America (Mexico) and the world: A systematic review and meta-analysis. Journal of Clinical Medicine. 2023;12(20):6583. https://doi.org/10.3390/jcm12206583ArticlePubMedPMC
• 19. Sarvepalli SM, Bailey BA, D'Alessio D, Lemaitre M, Vambergue A, Rathinavelu J, et al. Risk factors for the development or progression of diabetic retinopathy in pregnancy: Meta-analysis and systematic review. Clinical & Experimental Ophthalmology. 2023;51(3):195–204. https://doi.org/10.1111/ceo.14168ArticlePubMed
• 20. Grosso A, Cheung N, Veglio F, Wong TY. Similarities and differences in early retinal phenotypes in hypertension and diabetes. Journal of Hypertension. 2011;29(9):1667–1675. https://doi.org/10.1097/HJH.0b013e3283496655ArticlePubMed
• 21. The Korean Society of Hypertension. Clinical guidelines for hypertension [Internet]. Seoul: The Korean Society of Hypertension. 2022 [cited 2023 Dec 31]. Available from: https://www.koreanhypertension.org/reference/guide
• 22. Fraser-Bell S, Symes R, Vaze A. Hypertensive eye disease: A review. Clinical & Experimental Ophthalmology. 2017;45(1):45–53. https://doi.org/10.1111/ceo.12905ArticlePubMed
• 23. Chen X, Meng Y, Li J, She H, Zhao L, Zhang J, et al. Serum uric acid concentration is associated with hypertensive retinopathy in hypertensive Chinese adults. BMC Ophthalmology. 2017;17(1):83. https://doi.org/10.1186/s12886-017-0470-yArticlePubMedPMC
• 24. Moola S, Munn Z, Tufanaru C, Aromataris E, Sears K, Sfetcu R, et al. Systematic reviews of etiology and risk (2020). Aromataris E, Lockwood C, Porritt K, Pilla B, Jordan Z. In: JBI Manual for Evidence Synthesis [Internet] JBI. 2024. [cited 2024 Dec 20]. Available from: https://synthesismanual.jbi.global. https://doi.org/10.46658/JBIMES-24-06
• 25. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71ArticlePubMedPMC
• 26. Lefebvre C, Glanville J, Briscoe S, Featherstone R, Littlewood A, Metzendorf MI, et al. Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated October 2023) [Internet]. Cochrane. 2023. [cited 2023 Dec 31]. Available from: www.training.cochrane.org/handbook
• 27. Xuan J, Wang L, Fan L, Ji S. Systematic review and meta-analysis of the related factors for diabetic retinopathy. Annals of Palliative Medicine. 2022;11(7):2368–2381. https://doi.org/10.21037/apm-22-437ArticlePubMed
• 28. JBI. Checklist for analytical cross sectional studies: Critical Appraisal tools for use in JBI Systematic Reviews [Internet]. JBI. 2020 [cited 2023 Nov 5]. Available from: https://jbi.global/critical-appraisal-tools
• 29. Adar A, Onalan O, Sevik O, Turgut Y, Cakan F. Could aortic arch calcification help in detection of hypertensive retinopathy? Blood Pressure Monitoring. 2021;26(2):118–123. https://doi.org/10.1097/MBP.0000000000000498ArticlePubMed
• 30. Karadag B, Ozyigit T, Serindag Z, Ilhan A, Ozben B. Blood pressure profile is associated with microalbuminuria and retinopathy in hypertensive nondiabetic patients. Wiener Klinische Wochenschrift. 2018;130:204–210. https://doi.org/10.1007/s00508-017-1270-3ArticlePubMed
• 31. Kabedi NN, Mwanza JC, Lepira FB, Kayembe TK, Kayembe DL. Hypertensive retinopathy and its association with cardiovascular, renal and cerebrovascular morbidity in Congolese patients. Cardiovascular Journal of Africa. 2014;25(5):228–232. https://doi.org/10.5830/CVJA-2014-045ArticlePubMedPMC
• 32. Ozer S, Yucekul B, Yilmaz AS, Ozyildiz AG, Kinik M, Turan OE, et al. Epicardial fat thickness is associated with retinopathy in patients with newly diagnosed hypertension. Northern Clinics of Istanbul. 2021;8(4):365–370. https://doi.org/10.14744/nci.2020.23334ArticlePubMedPMC
• 33. Chillo P, Ismail A, Sanyiwa A, Ruggajo P, Kamuhabwa A. Hypertensive retinopathy and associated factors among nondiabetic chronic kidney disease patients seen at a tertiary hospital in Tanzania: A cross-sectional study. International Journal of Nephrology and Renovascular Disease. 2019;12:79–86. https://doi.org/10.2147/IJNRD.S196841ArticlePubMedPMC
• 34. Li J, Zhang W, Zhao L, Zhang J, She H, Meng Y, et al. Positive correlation between hypertensive retinopathy and albuminuria in hypertensive adults. BMC Ophthalmology. 2023;23(1):66. https://doi.org/10.1186/s12886-023-02807-6ArticlePubMedPMC
• 35. Zhang Y, Zhao L, Li H, Wang Y. Risk factors for hypertensive retinopathy in a Chinese population with hypertension: The Beijing eye study. Experimental and Therapeutic Medicine. 2019;17(1):453–458. https://doi.org/10.3892/etm.2018.6967ArticlePubMedPMC
• 36. Kangwagye P, Rwebembera J, Wilson T, Bajunirwe F. Microalbuminuria and retinopathy among hypertensive nondiabetic patients at a large public outpatient clinic in Southwestern Uganda. International Journal of Nephrology. 2018;2018:4802396. https://doi.org/10.1155/2018/4802396ArticlePubMedPMC
• 37. Thapa R, Das T. Risk stratification on systemic target organ involvement associated with hypertensive retinopathy. Journal of Nepal Health Research Council. 2023;20(3):577–585. https://doi.org/10.33314/jnhrc.v20i3.4273ArticlePubMed
• 38. Cuspidi C, Meani S, Valerio C, Fusi V, Catini E, Sala C, et al. Prevalence and correlates of advanced retinopathy in a large selected hypertensive population. The Evaluation of Target Organ Damage in Hypertension (ETODH) study. Blood Pressure. 2005;14(1):25–31. https://doi.org/10.1080/08037050510008805ArticlePubMed
• 39. Pugh D, Gallacher PJ, Dhaun N. Management of hypertension in chronic kidney disease. Drugs. 2019;79(4):365–379. https://doi.org/10.1007/s40265-019-1064-1ArticlePubMedPMC
• 40. Kaneyama A, Hirata A, Hirata T, Imai Y, Kuwabara K, Funamoto M, et al. Impact of hypertension and diabetes on the onset of chronic kidney disease in a general Japanese population. Hypertension Research. 2023;46(2):311–320. https://doi.org/10.1038/s41440-022-01041-9Article
• 41. Zhang C, Zhou L, Ma M, Yang Y, Zhang Y, Zha X. Dynamic nomogram prediction model for diabetic retinopathy in patients with type 2 diabetes mellitus. BMC Ophthalmology. 2023;23(1):186. https://doi.org/10.1186/s12886-023-02925-1Article
• 42. Li W, Song Y, Chen K, Ying J, Zheng Z, Qiao S, et al. Predictive model and risk analysis for diabetic retinopathy using machine learning: A retrospective cohort study in China. BMJ Open. 2021;11(11):e050989. https://doi.org/10.1136/bmjopen-2021-050989ArticlePubMedPMC
• 43. Jo K, Chang DJ, Min JW, Yoo YS, Lyu B, Kwon JW, et al. Long-term prediction models for vision-threatening diabetic retinopathy using medical features from data warehouse. Scientific Reports. 2022;12(1):8476. https://doi.org/10.1038/s41598-022-12369-0ArticlePubMedPMC
• 44. Wu YB, Wang CG, Xu LX, Chen C, Zhou XB, Su GF. Analysis of risk factors for progressive fibrovascular proliferation in proliferative diabetic retinopathy. International Ophthalmology. 2020;40(10):2495–2502. https://doi.org/10.1007/s10792-020-01428-yArticlePubMed
• 45. Cai X, Chen Y, Yang W, Gao X, Han X, Ji L. The association of smoking and risk of diabetic retinopathy in patients with type 1 and type 2 diabetes: A meta-analysis. Endocrine. 2018;62(2):299–306. https://doi.org/10.1007/s12020-018-1697-yArticlePubMed
• 46. Zhu C, Zhu J, Wang L, Xiong S, Zou Y, Huang J, et al. Development and validation of a risk prediction model for diabetic retinopathy in type 2 diabetic patients. Scientific Reports. 2023;13(1):5034. https://doi.org/10.1038/s41598-023-31463-5Article
• 47. Costa F, Soares R. Nicotine: A pro-angiogenic factor. Life Sciences. 2009;84(23-24):785–790. https://doi.org/10.1016/j.lfs.2009.03.002ArticlePubMed
• 48. Leone A. Biochemical markers of cardiovascular damage from tobacco smoke. Current Pharmaceutical Design. 2005;11(17):2199–2208. https://doi.org/10.2174/1381612054367391ArticlePubMed
• 49. Roerecke M, Kaczorowski J, Tobe SW, Gmel G, Hasan OSM, Rehm J. The effect of a reduction in alcohol consumption on blood pressure: A systematic review and meta-analysis. The Lancet Public Health. 2017;2(2):e108–e120. https://doi.org/10.1016/S2468-2667(17)30003-8ArticlePubMedPMC
• 50. Wong TY, Mitchell P. Hypertensive retinopathy. The New England Journal of Medicine. 2004;351(22):2310–2317. https://doi.org/10.1056/NEJMra032865ArticlePubMed

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