To examine the association between systemic hypertension (HTN) and primary open-angle glaucoma (POAG) using Taiwan’s nationwide health insurance claims data.
A case-control study.
Data for this case-control study were retrieved from the Taiwan National Health Insurance Research Database for all 112,929 newly diagnosed patients with POAG from January 2010 through December 2015 (cases), and 449,840 propensity score-matched controls from Taiwan’s National Health Insurance system. We performed multiple logistic regression analysis to estimate the odds (ORs) of prior HTN among cases vs controls.
Of total 562,300 study patients, 296,975 (52.81%) had HTN prior to the index date, 63,528 (56.49%) among cases and 233,447 (51.90%) among controls ( P < .001). POAG was significantly associated with prior HTN (OR 1.31, 95% CI 1.29-1.33) after adjusting for age, sex, monthly income, geographic location and residential urbanization level, hyperlipidemia, diabetes, coronary heart disease, migraine, hypotension, and obstructive sleep apnea syndrome.
POAG is associated with pre-existing HTN, suggesting that internal medicine/family medicine physicians should refer patients with hypertension periodically for regular ophthalmological examinations and ophthalmologists should alert patients with glaucoma to have their blood pressure regularly monitored.
Systemic hypertension (HTN) affects more than 25% of the adult population worldwide and is a major public health concern. , Although it is well established that HTN adversely affects the heart and the kidney, , its association with primary open-angle glaucoma (POAG) has been inconclusive. Glaucoma is the second leading cause of blindness globally, causing irreversible damage of the retinal ganglion cells and nerve fiber layer. The Blue Mountains Eye Study demonstrated a positive association between HTN and POAG. The Rotterdam study showed no association between systolic blood pressure and POAG, but high diastolic blood pressure was associated with increased risk of low pressure glaucoma. The Baltimore Eye Survey reported an increased risk of glaucoma with increasing (diastolic or systolic) hypertension. In contrast, the Barbados Eye Study found that HTN was not associated with prevalence of POAG at baseline. Further the relative risk of POAG decreased with increasing baseline systolic blood pressure levels. In light of these conflicting results, this study investigated the association of HTN with POAG using population-based nationwide data from Taiwan.
Data were retrieved from the Taiwan National Health Insurance (NHI) Research Database (NHIRD), which is a database of all NHI beneficiaries, over 99% of the Taiwanese population. This database includes the registration files and all medical claims data for approximately 23 million NHI enrollees since 1995 when the NHI program was implemented. The NHIRD provides de-identified data to Taiwanese researchers, enabling longitudinal studies of patients with medical conditions. A large volume of research has been published based on the NHIRD in peer-reviewed international journals. This study was approved by the Institutional Review Board of Taipei Medical University (TMU-JIRB N201912007). This study adhered to the Declaration of Helsinki.
This study used a retrospective case control design. To select cases, we first identified 122,025 patients with a first-time diagnosis of POAG appearing in a claim for a clinic visit or hospital outpatient department visit from January 1, 2010, to December 31, 2015 (ICD-9-CM codes 365.1, 365.10, and 365.11). We used a look-back period of 3 years to exclude patients with POAG appearing in any claim prior to the index date during the study period. We selected patients with at least 2 claims showing a POAG diagnoses and showing a prescription for topical antiglaucoma medications (for diagnostic validity) and assigned the date of first POAG diagnosis as their index date. We excluded 3,114 patients under 18 years of age because of the low prevalence of POAG and HTN in that age group. The analytic study sample included 112,929 cases with POAG.
To select controls, we first excluded all patients with a medical claim showing a POAG diagnosis during the study period or aged less than 18 years. Out of the remaining NHI beneficiaries we selected a comparison group (controls) similar to cases on demographic and comorbidity variables at baseline. We selected four controls per POAG case by propensity score matching (n = 449,840) using age, sex, monthly income, geographic location (northern, central, southern, and eastern) residential urbanization level, and selected comorbidities expected to be associated with either POAG or HTN, hyperlipidemia, diabetes, coronary heart disease, migraine, hypotension, and obstructive sleep apnea syndrome. We assigned the date of their first utilization of ambulatory care during the index year of the matched case as the control patient’s index date. The final study sample included 112,460 POAG patients and 449,840 patients without POAG as controls.
The exposure of interest was HTN preceding the index date (for cases, POAG diagnosis date, and for controls, date of the first ambulatory care claim during the year of diagnosis of their matched case). The outcome of interest was POAG. We identified prior HTN by ICD-9-CM codes 401-405 in ambulatory care visit claims prior to the index date. To strengthen diagnostic validity we identified HTN only if a prescription for antihypertensive medication could be found in the claims.
Analyses were performed using the SAS statistical package (SAS System for Windows, V.9.4, SAS Institute, Cary, NC, USA). We used chi-squared tests to compare cases and controls on sex, monthly income (<NT$15,841, 15,841-25,000, ≥25,001), geographic location (northern, central, eastern, and southern Taiwan), urbanization level (5 levels: 1 most urbanized and 5 least urbanized), hyperlipidemia, migraine, obstructive sleep apnea syndrome, diabetes, coronary heart disease, and hypotension between patients with POAG and their matched controls. We performed multiple logistic regression analysis were to estimate the odds (ORs) of prior HTN among cases vs controls. A value of P = .05 was used to determine statistical significance.
Table 1 presents the demographic characteristics and medical comorbidities of cases and controls. After selecting controls by propensity score matching, we found small but statistically significant differences in age, sex, monthly income, geographical location, and urbanization level of the patient’s residence between cases and controls (all P < .001), significance largely attributable to large sample size. Cases were also slightly more likely to have diabetes (30.3% vs 30.0%, P = .031), migraine (3.0% vs 2.6%, P < .001), hypotension (0.7% vs 0.4%, P < .001), obstructive sleep apnea syndrome (1.8% vs 1.4%, P < .001), and coronary heart disease (16.9% vs 16.6%, P = .024) than controls.
|Variable||Patients with Primary Open-Angle Glaucoma (n = 112,460)||Controls (n = 449,840)||P Value|
|Total no.||%||Total no.||%|
|Age, mean (standard deviation)||59.16 (16.23)||59.49 (16.29)||<.001|
|1 (most urbanized)||50,782||45.16||200,325||44.53|
|5 (least urbanized)||3,163||2.81||16,108||3.58|
|Obstructive sleep apnea syndrome||1,980||1.76||6,304||1.40||<.001|
|Coronary heart disease||19,030||16.92||74,859||16.64||.024|