Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Associations between retinal arteriolar and venular calibre with the prevalence of impaired fasting glucose and diabetes mellitus: A cross-sectional study.

BACKGROUND: This study aims to explore retinal vessel calibre in individuals at risk of coronary artery disease (CAD), diagnosed with impaired fasting glucose (IFG) or diabetes mellitus (DM), and whether indices of CAD extent and severity modifies these associations with DM. METHODS: A cross-sectional study was undertaken of 1680 patients presenting to Westmead Hospital (Sydney, Australia) for evaluation of potential CAD. Baseline digital retinal photographs, cardiovascular risk factor measurements, fasting blood tests and self-reported diabetes by patient questionnaire was recorded. Extent and severity of CAD was assessed using Extent and Gensini scores from angiography findings, respectively. Multivariate analysis including age and hypertension was undertaken to assess the association between retinal vessel calibre and IFG or DM. RESULTS: A total of 748 patients were included; 96 (12.8%) and 189 (25.3%), respectively, had IFG or DM (together termed 'hyperglycaemia'). No consistent association between hyperglycaemia and retinal arteriolar calibre was apparent. Wider retinal venular calibre (second and third tertile) carried a significantly higher odds of DM in men only (multivariable-adjusted OR 2.447, p = 0.005; and OR 2.76, p = 0.002; respectively). No equivalent association was apparent in women. This association was marginally significant (p = 0.08) in patients with CAD Extent scores below the median (i.e. less diffuse CAD). Retinal vessel calibre was not associated with impaired fasting glucose. CONCLUSIONS: This study reports a significant association between retinal venular widening and diabetes mellitus in men. This association was marginally stronger among participants with less diffuse CAD.

Chronic kidney disease and the severity of coronary artery disease and retinal microvasculature changes: a cross-sectional study.

BACKGROUND: Prior studies have suggested the association between incidence of coronary artery disease (CAD) with chronic kidney disease (CKD) and poor glomerular filtration function. However to the best of our knowledge, few studies have specifically assessed this relationship based on the severity of CAD as quantified using Extent and Gensini scores. METHODS: Between June 2009 and January 2012, data were collected from 1,680 participants as part of the Australian Heart Eye Study (AHES) cohort. Coronary angiograms were scored according to Gensini (severity) and Extent scores. Retinal vessel calibres were measured using validated semi-automated software. Potential confounders were adjusted for using multivariate analysis. RESULTS: There were no significant associations found between CKD status with Extent and Gensini scores for CAD severity, both unadjusted and when adjusted for confounding factors. In unadjusted analyses, a significant association between CKD and narrower retinal arteriolar diameter was observed (P=0.0072). After multivariate adjustment, the association between CKD and retinal arteriolar diameter was attenuated and was no longer significant (P=0.1466). No associations were observed between retinal venular calibre and prevalent CKD. CONCLUSIONS: The present study demonstrated no independent associations between CKD and CAD severity. These results warrant validation by future large, prospective longitudinal studies.

Severity of coronary artery disease and retinal microvascular signs in patients with diagnosed versus undiagnosed diabetes: cross-sectional study.

BACKGROUND: There is increasing evidence that a considerable proportion of patients with diabetes remain undiagnosed and untreated, however, it is unclear whether this is associated with more severe coronary artery disease (CAD) and microvasculature changes compared with diagnosed patients. We assessed CAD extent and severity, along with changes to the retinal microvascular structure in participants with undiagnosed versus diagnosed type 2 diabetes. METHODS: Participants of the Australian Heart Eye Study were stratified into participants with previously diagnosed diabetes (n=489), undiagnosed diabetes (n=76) and no diabetes (n=1,112). Retinal vessel caliber was measured from digital retinal images. Extent and severity of CAD was assessed using Extent and Gensini scores from angiography findings, respectively. RESULTS: Participants with undiagnosed and diagnosed diabetes versus those with no diabetes (reference group) had increased odds of being in the highest quartile of Gensini scores, multivariate adjusted odds ratios (OR) =7.02 [95% confidence interval (CI), 2.04-24.1] and OR =2.76 (95% CI, 1.67-4.55), respectively. Participants with undiagnosed and diagnosed diabetes versus those with no diabetes also had increased odds of being in the highest quartile of Extent scores, multivariate adjusted OR =7.63 (95% CI, 2.15-27.10) and OR =3.72 (95% CI, 2.22-6.27), respectively. No significant differences were observed in retinal vessel caliber between participants with undiagnosed versus diagnosed diabetes. CONCLUSIONS: The present study demonstrated that participants with undiagnosed diabetes compared to those with previously diagnosed diabetes, had a stronger likelihood of having more severe and extensive CAD. However, retinal microvascular signs did not differ by diabetes status.

Metabolic syndrome and retinal microvascular calibre in a high cardiovascular disease risk cohort.

AIMS: To investigate the independent associations between metabolic syndrome and retinal vessel calibre in a high cardiovascular risk cohort, and to determine whether these associations also exist in patients without diabetes, hypertension or coronary artery disease (CAD). METHODS: The Australian Heart Eye Study is an observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Metabolic syndrome was defined according to the Third Report of the National Cholesterol Education Program. Retinal arteriolar calibre narrowing and retinal venular calibre widening were measured from retinal photographs. CAD was quantified using severity (Gensini) and extent scores. Diabetes and hypertension were defined from clinical investigation (fasting plasma glucose >7.0 mmol/L and blood pressure >130/85 mm Hg) or from self-reported clinical diagnosis, including the use of medications. RESULTS: A total of 979 participants had complete information on metabolic syndrome components and were included in cross-sectional analyses. After adjusting for age, sex, smoking status and fellow vessel calibre, persons with metabolic syndrome (compared with persons without metabolic syndrome) had narrower retinal arteriolar calibre (mean difference 4.3 µm, p<0.0001). No significant difference in venular calibre was observed (p=0.05). This association persisted in persons without diabetes (mean arteriolar calibre difference 4.4 µm, p=0.0006) but not in participants without CAD and those without hypertension. CONCLUSIONS: Metabolic syndrome is independently associated with narrower retinal arterioles but not wider retinal venules among those at high risk of CAD. The association between metabolic syndrome and narrower retinal arterioles is likely due to the presence of CAD or hypertension in individuals with this syndrome, as the association is not significant in individuals without hypertension or without CAD.

Association between Retinal Arteriolar and Venule Calibre with Prevalent Heart Failure: A Cross-Sectional Study.

BACKGROUND: There is evidence to suggest that microvascular disease, particularly diabetic retinopathy, plays a role in the pathogenesis of HF. However, whether changes in retinal vessel calibre predicts HF is unclear. The purpose of this study was to examine the association of retinal microvascular structure with prevalent heart failure (HF). METHODS: The Australian Heart Eye Study (AHES) is a cross-sectional study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential coronary artery disease by coronary angiography. Retinal vessel calibre was graded using retinal photography and participants' self-reported echocardiography-confirmed HF was obtained via an extensive medical questionnaire. RESULTS: There were 107 participants (8.1%) with prevalent self-reported HF. Persons with wider retinal arteriolar calibre (comparing highest versus lowest tertile or reference) were more likely to have prevalent HF (OR 3.5; 95% CI, 1.7-7.2) when adjusted for age and sex. After further adjustment for body mass index, hypertension, diabetes, smoking status, triglycerides and estimated glomerular filtration rate, this association remained significant (OR 4.5; 95% CI, 2.0-9.8). After further stratification, this association remained significant among participants with diabetes (OR 10.3; 95% CI, 2.7-39.3) but not in those without diabetes (OR 2.7; 95% CI, 0.9-7.5). The strength of this association was not dependent on the length of history of diabetes, or retinopathy status. There was no significant association between retinal venular calibre and prevalence of HF. CONCLUSIONS: Wider retinal arteriolar diameter was significantly and independently associated with prevalent HF in participants of a cross-sectional study. This association was significant stronger among participants with diabetes compared to without diabetes. No association was found between retinal venule calibre with prevalent HF.

Prevalence and risk factors of epiretinal membrane in a cohort with cardiovascular disease risk, compared with the Blue Mountains Eye Study.

AIMS: To describe the prevalence of idiopathic and secondary epiretinal membranes (ERM) in a clinical cohort (Australian Heart Eye Study, AHES) and compare to the Blue Mountains Eye Study, and to determine whether associations exist between idiopathic ERM and the extent and severity of coronary artery disease (CAD). METHODS: The AHES is an observational study that surveyed 1680 participants who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Severity and extent of CAD was assessed using three scoring systems: (1) segment/vessel scores, (2) Gensini and (3) extent scores. Two types of ERM were identified: a more severe form, termed 'preretinal macular fibrosis' (PMF) in which retinal folds were identified; and a less severe form termed 'cellophane macular reflex' (CMR), without visible retinal folds. RESULTS: Overall prevalence of ERM was 7.0% (n=115), with CMR and PMF each 3.5%. 72.7% of ERM cases were idiopathic (no secondary cause identified). Prevalence of PMF, but not CMR, was significantly higher than the corresponding age-standardised prevalence in the baseline Blue Mountains Eye Study (p<0.001). There was no significant association between extent and severity of CAD and idiopathic ERM. CONCLUSIONS: This study suggests that cardiovascular disease (specifically severity and extent of CAD) is not associated with ERM. However, there may be a greater prevalence of severe ERM (PMF) in a high cardiovascular risk cohort relative to a population-based cohort.

Gender differences in the severity and extent of coronary artery disease.

OBJECTIVE: To investigate whether women presenting with suspected angina would show less severe coronary artery disease in than men as determined by the extent score. METHODS: We examined 994 participants of the Australian Heart Eye Study presenting for coronary angiography in the investigation of chest pain from June 2009 to February 2012. People were excluded if there was a history of coronary artery bypass surgery, previous stenting procedure or incomplete angiogram scoring. An extent and vessel score was calculated using invasive coronary angiography. Normal coronary arteries were defined as having no luminal irregularity (Extent score = 0). Obstructive coronary artery disease was defined as a luminal narrowing of greater than 50%. RESULTS: Women compared to men without infarction had a lower burden of CAD with up to 50% having normal coronary arteries in the 30-44 year group and 40% in the 45-59 year group. Compared to men, women with chest pain had lower mean extent scores (19.6 vs 36.8; P < 0.0001) and lower vessel scores (0.7 v 1.3; P < 0.0001). Although the mean extent score was lower in women than men with myocardial infarction, this was not statistically significant (34.8 vs 41.6 respectively; P = 0.18). CONCLUSION: There is a marked difference in coronary artery disease severity and burden between females and males presenting for the investigation of suspected angina. Women are more likely to have normal coronary arteries or less severe disease than age-matched men, particularly if they do not present with myocardial infarction.

Severity of coronary artery disease is independently associated with the frequency of early age-related macular degeneration.

BACKGROUND/AIMS: To describe the prevalence of early, late and any age-related macular degeneration (AMD) in a clinical cohort (Australian Heart Eye Study, AHES) and to determine whether associations exist between extent and severity of coronary artery disease (CAD) and AMD, independent of traditional cardiovascular risk factors. METHODS: The AHES is an observational study that surveyed 1680 participants between 2009 and 2012 who presented to a tertiary referral hospital for the evaluation of potential CAD by coronary angiography. Severity and extent of CAD was assessed using three scoring systems: (1) segment/vessel scores, (2) Gensini and (3) extent scores. RESULTS: Prevalence of early and late AMD was 5.8% (n=86) and 1.4% (n=21), respectively. After multivariable adjustment, patients with stenosis >50% in any coronary artery segment (vessel score) had approximately twofold higher odds of early AMD, OR 1.95 (95% CI 1.07 to 3.57). Patients with obstructive coronary stenosis in all three main coronary arteries (segment score) had greater than twofold higher likelihood of early AMD, OR 2.67 (95% CI 1.24 to 5.78). Participants in the highest versus lowest tertile of Gensini scores were also twice as likely to have early AMD, multivariable-adjusted OR 2.27 (95% CI 1.12 to 4.58). Extent scores were not associated with AMD. There was no significant association between CAD and late AMD. CONCLUSIONS: Severity of coronary stenosis and the presence of stenotic lesions were independently associated with early AMD. These findings could have potential clinical significance as they suggest that individuals with evidence of CAD may be screened for early AMD.

Associations between retinal microvascular structure and the severity and extent of coronary artery disease.

OBJECTIVE: Microvascular mechanisms are increasingly recognized as being involved in a significant proportion of coronary artery disease (CAD) cases, but their exact contribution or role is unclear. We aimed to define the association between retinal microvascular signs and both CAD extent and severity. METHODS: 1120 participants of the Australian Heart Eye Study were included. Retinal vessel caliber was measured from digital retinal images. Extent and severity of CAD was assessed using several approaches. First, a simple scoring classifying participants as having one-vessel, two-vessel, and three-vessel disease was used. Gensini and Extent scores were calculated using angiography findings. RESULTS: After multivariable adjustment, significantly narrower retinal arteriolar caliber in women (comparing lowest versus highest quartile or reference) and wider venular caliber in men (comparing highest versus lowest quartile or reference) were associated with 2-fold and 54% higher odds of having at least one stenosis ≥50% in the epicardial coronary arteries, respectively. Women in the third versus first tertile of retinal venular caliber had 92% and ∼2-fold higher likelihood of having higher Gensini and Extent scores, respectively. Women in the lowest versus highest tertile of retinal arteriolar caliber had greater odds of having higher Extent scores, OR 2.99 (95% CI 1.45-6.16). In men, non-significant associations were observed between retinal vascular caliber and Gensini and Extent scores. CONCLUSIONS: An unhealthy retinal microvascular profile, namely, narrower retinal arterioles and wider venules was associated with more diffuse and severe CAD among women.