Preventive cardiology
Relation of Corneal Arcus to Cardiovascular Disease (from the Framingham Heart Study Data Set)

https://doi.org/10.1016/j.amjcard.2008.08.030Get rights and content

Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary artery disease (CAD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and CAD. A prospective analysis was performed using Cox proportional-hazards regression models in the Framingham Heart Study Original Cohort and Offspring Cohort database. This cohort included 23,376 patient-examinations, during 3,890 (17%) of which corneal arcus was identified. Corneal arcus was a predictor of CVD and CAD at 4 years (hazard ratios [HRs] 2.28 and 1.99, respectively) and 8 years (HRs 2.52 and 2.35, respectively) of follow-up (p <0.0001 for all). Corneal arcus was no longer predictive of either CVD or CAD, however, after adjustment for age and gender at 4 years (HRs 1.07 and 1.01, respectively) and 8 years (HRs 1.18 and 1.17, respectively) of follow-up (p >0.05 for all). In conclusion, corneal arcus predicted CVD and CAD in the community-based Framingham Heart Study cohort because of the strong association of corneal arcus with increasing age. To date, this is the largest and lengthiest population-based cohort study examining the direct association between corneal arcus and CVD and CAD.

Section snippets

Methods

The Framingham study was initiated in 1948 as a prospective study of the incidence of clinical coronary artery disease (CAD) in men aged 30 to 60 years. An initial cohort of 5,209 participants (the Original Cohort) was examined at initial visits and reexamined every 2 years by the Framingham Heart Study staff. The offspring of the Original Cohort (the Offspring Cohort), consisting of 5,124 participants, were examined every 4 years (except for an 8-year gap between the first and second

Results

Characteristics of the baseline exam for each cohort are listed in Table 1. In the Original Cohort, baseline mean values for age (64 years), systolic blood pressure (138 mm Hg), total cholesterol (232 mg/dl), and corneal arcus prevalence (28%) were higher than in the Offspring Cohort. The Offspring Cohort had larger percentages of men (47%) and current smokers (35%).

Corneal arcus at 4 and 8 years was significantly related to CVD (Table 2) and CAD events (Table 3). The hazard ratios (HR) were

Discussion

The results of the present study do not demonstrate that corneal arcus is an independent risk predictor for CVD and CAD. When analyzed by crude HRs, corneal arcus does predict CVD and CAD risk, but this value depends on the association of arcus with age.

The borderline p value and confidence intervals in the adjusted model of CVD risk prediction at 8 years might represent a trend toward statistical significance. Although a larger sample population might have affected this number toward a

References (25)

  • J.H. Nishimoto et al.

    Corneal arcus as an indicator of hypercholesterolemia

    J Am Optom Assoc

    (1990)
  • L.E. Chambless et al.

    The association of corneal arcus with coronary heart disease and cardiovascular disease mortality in the Lipid Research Clinics Mortality Follow-Up Study

    Am J Publ Health

    (1990)
  • Cited by (27)

    • The value of physical signs in identifying patients with familial hypercholesterolemia in the era of genetic testing

      2020, Journal of Cardiology
      Citation Excerpt :

      Epidemiologic studies examining the association between corneal arcus and CAD have yielded mixed results. Analysis from the Framingham Heart Study, the largest and lengthiest population-based cohort study, which examined the association between corneal arcus and CVD showed that corneal arcus was a predictor of CAD or CVD at 4 and 8 years of follow-up but lost its association after adjustment for age and gender [38]. The Copenhagen City Heart Study, a prospective population-based cohort study, found no association of corneal arcus with CVD during a mean follow-up of 22 years [30].

    • History and Physical Examination

      2018, Chronic Coronary Artery Disease: A Companion to Braunwald's Heart Disease
    • Detecting familial hypercholesterolemia by serum lipid profile screening in a hospital setting: Clinical, genetic and atherosclerotic burden profile

      2018, Nutrition, Metabolism and Cardiovascular Diseases
      Citation Excerpt :

      Rouhiainen et al. and other authors found a significant association between IMT and corneal arcus in hypercholesterolemic patients [36,37]. Other authors did not support this hypothesis and reported that corneal arcus predicts CVD and CHD in the community-based Framingham Heart Study cohort due to the strong association of corneal arcus with increasing age [38]. A possible explanation to support the association of IMT and corneal arcus may be that the last one could reflect a continuous exposure to high LDL cholesterol levels.

    • Is Corneal Arcus Independently Associated With Incident Cardiovascular Disease in Asians?

      2017, American Journal of Ophthalmology
      Citation Excerpt :

      Other longitudinal findings in whites have not shown consistent results. For example, the Framingham Heart Study found no significant associations of baseline CA with incident CVD and CHD after adjusting for age and sex,10 while others have reported that baseline CA was independently associated with incident CVD only in younger men <50 years of age.3,11,14 We also found an independent association of CA in incident CVD in men, but our study was consistent across all age groups.

    • History and Physical Examination

      2017, Chronic Coronary Artery Disease: A Companion to Braunwald's Heart Disease
    • ApoL1 levels in high density lipoprotein and cardiovascular event presentation in patients with familial hypercholesterolemia

      2016, Journal of Lipid Research
      Citation Excerpt :

      Cox proportional hazards analysis (stepwise selection of variables) was performed to assess the potential impact of age, lipid-related variables (including total cholesterol, LDL-C, HDL-C, TG, apoA-I, apoB, and apoL1 levels), and corneal arcus in the survival rate in FH patients treated to guidelines after suffering an ischemic cardiac event 3.5 years later (N = 73; Table 3). The presence/absence of corneal arcus was included in the model as it has been previously described that this typical symptom of FH is associated with a higher CVD risk (52), and our discovery proteomic analysis revealed that FH patients with corneal arcus showed significantly lower total apoA-IV, apoL1, and PON1 contents, as well as a decreasing trend in LCAT levels (supplementary Table 6), when compared with those without. There were no significant differences in the duration of statin treatment between patients with corneal arcus and those without this typical sign of FH (P = 0.324).

    View all citing articles on Scopus

    This work was supported by Contract No. N01-HC-25195 from the the National Heart, Lung and Blood Institute, Bethesda, Maryland, Framingham Heart Study.

    View full text