Frequency of fish consumption, retinal microvascular signs and vascular mortality

OBJECTIVE: Fish consumption has established cardiovascular and cerebrovascular benefits, but its effects on microvascular structure have not been examined in population-based studies. We investigated this association, in relation to vascular mortality in an Australian cohort (1992-2004). METHODS: Of 3654 participants aged 49+ years, 2683 (73%) with available data were included. Retinal arteriolar and venular diameters were measured, and signs of arterio-venous nicking and retinopathy were assessed from digital retinal images. Fish consumption was evaluated using a food frequency questionnaire. RESULTS: Both wider mean arteriolar diameter (p = 0.002) and narrower venular diameter (p = 0.02) were associated with increasing frequency of consuming any or oily fish, after adjusting for cardiovascular risk factors, diet, inflammatory factors and socioeconomic status. This association was mainly present in persons with hypertension. Greater frequency of fish consumption was associated with a reduced prevalence of arterio-venous nicking and a borderline significant trend for reduced retinopathy prevalence. Ten year stroke-related mortality was significantly lower in persons consuming fish at least once per week compared to less frequent consumption (hazard ratio 0.57, 95% CI: 0.35 to 0.93). CONCLUSIONS: Recent evidence shows that narrower arterioles and wider venules may predict vascular events. Our new findings suggest that the vascular protective effects of consuming fish could act, in part, by preventing pathological microvasculature change.     

Body mass index and its effects on retinal vessel diameter in 6-year-old children

PURPOSE: To examine the relationship between body mass index (BMI) and other anthropometric measures with retinal vessel diameter in children. METHODS: A random cluster sample of 34 schools was selected in the Sydney metropolitan area during 2003-04, and 1740 children aged 6 years participated in The Sydney Childhood Eye Study. Retinal images were taken and vessel diameter was measured using a computer-imaging program. Anthropometric measures, including weight, height, waist circumference, BMI and body surface area (BSA), were obtained and defined using standardized protocols. Data on confounders, including ocular parameters, ethnicity, birth parameters and blood pressure, were similarly collected. RESULTS: Mean BMI was 16.2 kg/m(2) (+/-2.1 s.d.) in 1608 (92.4%) children with complete data. After controlling for age, sex, ethnicity, axial length of the eyeball, birth weight and mean arterial blood pressure, children with BMI above the cardiovascular risk threshold (defined as BMI>16.1 kg/m(2) in boys and BMI>15.9 kg/m(2) in girls) had mean retinal venular diameter 2.1 microm larger than those with BMI below this threshold (P=0.026). Increasing weight and BSA were also positively associated with wider retinal venules. Children in the highest quartile of BMI had mean retinal arteriolar diameter 2.2 microm smaller than those in the lowest quartile. Increasing waist circumference and shorter height were also associated with narrower retinal arterioles. CONCLUSIONS: In this sample of 6-year-old children, greater BMI, weight and BSA were associated with wider retinal venules, while greater BMI and larger waist circumference were associated with narrower retinal arterioles. These findings suggest a possible effect of increased body mass and adiposity on early microvascular structural alterations in childhood, long before the development of cardiovascular disease.     

Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons. METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods. RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7%; 95% confidence interval [CI], 8.7%-15.8%, vs 8.1%; 95% CI, 5.7%-11.6%), comparing largest with smallest venular caliber quartiles, and stroke (8.4%; 95% CI, 6.0-11.7, vs 5.8%; 95% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95% CI, 0.5-2.2; P = .73). CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.     

Lower dairy products and calcium intake is associated with adverse retinal vascular changes in older adults

Background and aimsHigher consumption of dairy products and calcium is likely to play a role in maintaining optimal vascular health. In this study, we aimed to explore the associations between consumption of total-, regular- and low-fat dairy foods, and total calcium intake with retinal vascular caliber.Methods and results2813 Blue Mountains Eye Study participants aged 50+ years had dietary data collected using a semi-quantitative food frequency questionnaire, and serves of dairy consumption were calculated. Fundus photographs were taken and retinal vascular caliber measured using computer-assisted techniques and summarized. After adjusting for age, sex, body mass index, smoking, mean arterial blood pressure, serum glucose, white cell count, history of diagnosed hypertension, stroke and coronary heart disease, plus retinal arteriolar caliber, participants in the lowest quintile of total dairy consumption compared to those in the remaining highest 4 quintiles had significantly wider retinal venular caliber, 227.2 versus 224.7 μm, respectively (multivariable-adjusted p = 0.002). Also, subjects in the lowest quintile of low-fat dairy product consumption versus those in the remaining quintiles of low-fat dairy intake had wider retinal venules (∼1.7 μm, p = 0.03) and narrower retinal arterioles (∼1.4 μm, p = 0.04). Participants in the lowest quintile versus highest quintile of total dietary calcium intake had ∼2.3 μm wider retinal venules (multivariable-adjusted p-trend = 0.02).ConclusionsA significant association was observed between lower intake of dairy products or calcium and adverse retinal vascular signs. We cannot discount the possibility of confounding from unmeasured risk factors; hence, further studies are warranted to confirm these findings.     

Retinal vascular caliber and the long-term risk of diabetes and impaired fasting glucose: the Blue Mountains Eye Study

Objective: To assess the associations of retinal vessel caliber with the 10‐year incidence of diabetes and impaired fasting glucose (IFG). Methods: The Blue Mountains Eye Study is a population based cohort study of Australian residents aged at least 49 years, with baseline examinations conducted during 1992–4. Retinal arteriolar and venular calibers were measured and summarized from baseline digitized images in 3368 participants. Diabetes was defined as a physician‐diagnosis of diabetes or fasting blood glucose ≥ 126 mg/dL and IFG as fasting blood glucose 109 to 125 mg/dL. Ten year incidence of diabetes and IFG was defined from 5‐ and 10‐year follow up data. Results : After adjusting for age and gender, wider retinal venular caliber was associated with an increased incidence of diabetes and IFG. These associations were not significant after controlling for baseline glucose, body mass index and other factors. In persons 49–70 years of age at baseline, however, the association of wider retinal venular caliber and incident IFG persisted after further controlling for other factors (OR, 1.53, 95% CI, 1.11–2.12). Retinal arteriolar caliber was not associated with incident diabetes or IFG. Conclusions: This study suggests that wider retinal venular caliber was associated with higher risk of IFG in middle‐aged persons.     

Impact of current and past blood pressure on retinal arteriolar diameter in an older population

OBJECTIVE: To examine the effects of current and past blood pressure on retinal arteriolar diameter in a general older population. DESIGN: Cross-sectional and longitudinal studies. SETTING: Population-based cohort study of older residents from an area west of Sydney, Australia. PARTICIPANTS: Two thousand three hundred and thirty-five individuals (n = 2335) (aged > or = 54 years) who attended the 5-year follow-up Blue Mountains Eye Study during 1997-99. MAIN OUTCOME MEASURES: A computer-assisted method measured vessel diameters from digitized right eye retinal photographs. The narrowest quintile of central retinal arteriolar equivalent or arteriole-to-venule ratio (AVR) defined generalized arteriolar narrowing. Blood pressure was measured using a mercury sphygmomanometer. RESULTS: After simultaneous adjustment for age, sex, body mass index, smoking and current or past blood pressure, elevated levels of both current and past blood pressure were associated with narrower retinal arterioles [Ptrend = 0.009 and 0.007 for current and past systolic blood pressure (SBP), respectively] and lower AVR [Ptrend = 0.001 and 0.0009 for current and past diastolic blood pressure (DBP), respectively]. Generalized arteriolar narrowing was associated with both current blood pressure [adjusted odds ratio (OR) 2.4, 95% confidence interval (CI) 1.5-3.8 for the highest versus lowest quintile of current DBP] and past blood pressure (adjusted OR 1.7, 95% CI 1.1-2.6, for the highest versus lowest quintile of past DBP). Hypertension duration or control status at baseline had no additional effect on arteriolar diameter after adjusting for current blood pressure. CONCLUSIONS: Our data document the independent effects of both current and past blood pressure on small vessel calibre in the retina, suggesting that retinal arteriolar narrowing may result from the cumulative effects of long-standing hypertension.     

Retinal microvasculature measurements in full-term newborn infants

Objective

Currently, there are no published data on retinal microvasculature size in human infants born at term. The purpose of this study was to determine the normal retinal microvasculature measurements in human infants born at term with normal birth weight and to compare these results with measurements in children and adults.

Methods

Retinal arteriole and venule measurements were obtained in a cohort of 20 full-term infants. Digital retinal images were obtained from both eyes after pupillary dilation using a digital retinal camera. Measurements of vessel diameter were then obtained using semi-automated software.

Results

Twenty infants (9 female infants and 11 male infants) were analyzed. The retinal arteriole diameter was 66.8-123.0 μm (mean, 85.5 (14.3) μm), and the venule diameter was 102.0-167.8 μm (mean, 130.0 (16.0) μm). There were no differences in the arterial or venule diameters between the male and female infants (83.2 (12.2) vs. 88.3 (16.9); P = 0.4372; 124.3 (16.0) vs. 137.0 (18.0); P = 0.08). The arteriovenous ratio was found to be 0.66 (95% CI 0.62-0.71). The coefficient of correlation between the retinal arterioles and venules was 0.56. The retinal arteriole and venule diameters increase as a person matures. The arteriovenous ratio also increases with age.

Conclusion

In newborn infants, retinal venules are significantly larger than retinal arterioles. The arteriovenous ratio is smaller in neonates compared to adults indicating the retinal arteriole diameter increases at a different pace compared to retinal venule. Sex does not influence the retinal microvasculature size in infants. The presence of spontaneous retinal hemorrhage and the inability to account for refractive errors were the main limitations of this study.     

Retinal microvasculature measurements in full-term newborn infants

ObjectiveCurrently, there are no published data on retinal microvasculature size in human infants born at term. The purpose of this study was to determine the normal retinal microvasculature measurements in human infants born at term with normal birth weight and to compare these results with measurements in children and adults.MethodsRetinal arteriole and venule measurements were obtained in a cohort of 20 full-term infants. Digital retinal images were obtained from both eyes after pupillary dilation using a digital retinal camera. Measurements of vessel diameter were then obtained using semi-automated software.ResultsTwenty infants (9 female infants and 11 male infants) were analyzed. The retinal arteriole diameter was 66.8–123.0 μm (mean, 85.5 (14.3) μm), and the venule diameter was 102.0–167.8 μm (mean, 130.0 (16.0) μm). There were no differences in the arterial or venule diameters between the male and female infants (83.2 (12.2) vs. 88.3 (16.9); P = 0.4372; 124.3 (16.0) vs. 137.0 (18.0); P = 0.08). The arteriovenous ratio was found to be 0.66 (95% CI 0.62–0.71). The coefficient of correlation between the retinal arterioles and venules was 0.56. The retinal arteriole and venule diameters increase as a person matures. The arteriovenous ratio also increases with age.ConclusionIn newborn infants, retinal venules are significantly larger than retinal arterioles. The arteriovenous ratio is smaller in neonates compared to adults indicating the retinal arteriole diameter increases at a different pace compared to retinal venule. Sex does not influence the retinal microvasculature size in infants. The presence of spontaneous retinal hemorrhage and the inability to account for refractive errors were the main limitations of this study.     

Serum uric acid and long-term mortality from stroke, coronary heart disease and all causes.

BACKGROUND: Increased serum uric acid (SUA) levels are linked to obesity, dyslipidemia, diabetes and hypertension. Whether SUA carries a risk for coronary heart disease (CHD) and stroke remains uncertain. DESIGN: A prospective cohort study. METHODS: Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years, 9125 men, free of CHD at entry, are included in this study. Subjects were divided into quintiles according to baseline SUA levels. Hazard ratios (HR) for all-cause, CHD, and stroke mortality were estimated in SUA quintiles, with the third serving as a referent. RESULTS: During follow-up, 2893 deaths were recorded, including 830 ascribed to CHD and 292 to stroke. The HR for all death [1.22, 95% confidence interval (CI) 1.09-1.37] and CHD (1.29, 95% CI 1.05-1.58) were increased in the upper SUA quintile. Fatal stroke showed a U-shaped relationship as both the upper (HR 1.48, 95% CI 1.02-2.17) and bottom (HR 1.43, 95% CI 0.99-2.08) quintiles were associated with a higher risk. Adjustment for confounders reduced the HR of the upper quintile for all outcomes, but did not attenuate the association of the bottom quintile with stroke (HR 1.52, 95% CI 1.04-2.23). When analysed separately by stroke type, the latter association seemed to be stronger for hemorrhagic (HR 3.27, 95% CI 1.14-9.33) than for ischemic stroke (HR 1.34, 95% CI 0.87-2.05). CONCLUSION: In addition to findings supporting increased mortality among hyperuricemic subjects, we identified an association between low SUA levels and fatal stroke, which deserves further investigation.     

Plasma asymmetric dimethylarginine and retinal vessel diameters in middle-aged men

It has been suggested that asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is linked to hypertension and vascular reactivity. Retinal arteriolar narrowing has been observed to associate early with increased risk of hypertension. The objective of this study was to evaluate the role of ADMA as a biomarker for early vascular changes of retinal vessels and thus as a possible biomarker of hypertension risk. Thirty-five healthy white men aged 50.1 years (range, 45-55 years) were studied. Using digitized fundus photography, the following diameters of retinal arterioles and venules were measured 1 disc diameter from the optic disc edge: the mean arteriole width (MAW) and venule width (MVW), the sum of squares of widths of arterioles (SSWA) and venules (SSWV), and the central retinal artery equivalent (CRAE) and venous equivalent (CRVE). Arteriovenous ratio was determined using MAW/MVW, SSWA/SSWV, and CRAE/CRVE. Blood pressure was measured by 24-hour ambulatory recordings and also by resting measurements. Plasma ADMA was determined by a high-performance liquid chromatography tandem mass spectrometry. Plasma ADMA had a strong negative association with MAW, MVW, SSWA, SSWV, CRAE, and CRVE. Arteriovenous ratio measurements did not associate with plasma ADMA or with l-arginine to ADMA ratio, but arteriovenous ratios had a strong association with blood pressure. In a multivariate linear model, plasma ADMA concentration was the most significant predictor of arteriole and venule diameter measurements. These results suggest that plasma ADMA is associated with vascular phenomenon seen in early hypertension and that ADMA may be a potential biomarker candidate for development of hypertension.     

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.     

Acute and chronic effects of marathon running on the retinal microcirculation

Objective

Previous studies indicate an association between marathon running and premature atherosclerosis. Retinal vessel diameter alterations, in particular narrower arterioles and wider venules, reflect early stages of atherosclerosis, but the influence of marathon on the retinal microcirculation is unknown.

Methods

Retinal vessel diameters were measured in 85 male runners (age 31–60 years; previous marathons 0–56) and in 45 age-matched healthy controls using a static vessel analyzer. In runners, diameters were also measured immediately and 24 h after a marathon. Cardiovascular risk profiles, clinical chemistry and, in a subgroup of 46 runners, peripheral arterial wave reflections were also assessed.

Results

Runners had larger arterioles (median 196 μm (IQR 25) vs. 190(25); p = 0.068) and smaller venules (222(25) vs. 224(18); p = 0.063) than controls, resulting in a significantly increased arteriolar-to-venular ratio (AVR; 0.89(0.08) vs. 0.85(0.07); p < 0.001). In runners, retinal vessel diameters were not associated with body mass index, blood pressure, smoking, lipids or training history, and no differences were observed between the lowest (0.71–0.84) and highest (0.95–1.06) AVR quintiles. The marathon run induced a significant increase of AVR (0.91 (0.09); p = 0.007) due to larger arteriolar than venular dilatations, correlating weakly to race duration (r = 0.32; p = 0.003) and to a lower increase in leucocytes (r = −0.35; p = 0.001). Vessel diameters normalized 24 h after the race. Augmentation index and pulse pressure decreased significantly after the race, but no associations with retinal vessel diameters were observed.

Conclusion

Marathon running is not associated with an impairment of the retinal microcirculation. These findings contrast previous reports on atherosclerotic alterations of peripheral vessels.     

Triglycerides + high-density-lipoprotein-cholesterol dyslipidaemia, a coronary risk factor in elderly women: the CArdiovascular STudy in the ELderly

BACKGROUND: The relationship between serum triglycerides (TG) level and the risk of coronary heart disease (CHD) mortality remains controversial. AIMS: To evaluate whether TG level is a risk factor for CHD in elderly people from general population, and to look for interactions between TG and other risk factors. METHODS: 3257 subjects aged >or= 65 years followed up for 12 years from the CArdiovascular STudy in the ELderly. Blood tests and anthropometric measurements were performed. Continuous items were divided into quintiles and, for each quintile, adjusted hazard ratio (HR) with 95% confidence interval (CI) for CHD mortality was derived by genders from Cox analysis. RESULTS: In women, the HR of being in the fifth rather than in the first quintile of TG was 2.45 (CI 1.48-3.51). In turn, high-density-lipoprotein cholesterol (HDL-C) inversely predicted CHD mortality; the HR of being in the first rather than in the fifth quintiles of HDL-C was 1.52 (CI 1.24-2.36). The risk of CHD mortality further increased up to 3.81 (CI 1.62-5.43) when high TG and low HDL-C were combined. No predictive role for either TG or HDL-C was detected in men. CONCLUSIONS: TG and HDL-C were independent predictors of CHD mortality in elderly women. The combination high TG + low HDL-C quadrupled the risk of CHD mortality in this gender only.     

Retinal arteriolar narrowing, hypertension, and subsequent risk of diabetes mellitus

BACKGROUND: Microvascular disease and hypertension have been linked with risk of diabetes mellitus. We examined the association of retinal arteriolar narrowing, a marker of chronic hypertension, with incident diabetes. METHODS: Prospective cohort study of 3251 nondiabetic persons aged 43 to 86 years living in Wisconsin. The diameters of retinal vessels were measured from baseline retinal photographs of participants. Retinal measurements were summarized as the retinal arteriole-to-venule ratio, with smaller ratios indicating narrower arteriolar diameters. Incident diabetes cases were ascertained at the 5-year and 10-year follow-up examinations. RESULTS: There were 249 incident diabetes cases. Participants with narrower retinal arteriolar diameters had a higher incidence of diabetes (cumulative incidences of 5.1%, 7.0%, 9.2%, and 11.7%, comparing decreasing quartiles of arteriole-to-venule ratio). After controlling for baseline casual blood glucose level, glycosylated hemoglobin level, body mass index, and other risk factors, retinal arteriolar narrowing was significantly associated with risk of incident diabetes (multivariable-adjusted relative risk, 1.53; 95% confidence interval, 1.03-2.27; comparing smallest to largest arteriole-to-venule ratio quartiles). Participants with both hypertension and retinal arteriolar narrowing had a 3-fold higher risk of incident diabetes (multivariable-adjusted relative risk, 3.41; 95% confidence interval, 1.66-6.98) than normotensive participants without arteriolar narrowing. CONCLUSIONS: Retinal arteriolar narrowing is related to risk of incident diabetes. These data suggest a possible link between systemic arteriolar narrowing associated with hypertension and diabetes development.     

Does hormone replacement therapy influence retinal microvascular caliber?

Previous population-based data suggest that retinal arteriolar diameter is wider in women than in men. Estrogen exposures could account for this difference. To evaluate the effects of HRT on small blood vessels, we assessed the relationship between use of hormone replacement therapy (HRT) and retinal microvascular diameter in older women in the Blue Mountains Eye Study baseline population (n = 1993, age >/= 49 years). Information on HRT use was recorded by trained interviewers. A computer-assisted program measured retinal vessel diameters from digitized photographs. Average arteriolar diameter was calculated as the central retinal arteriolar equivalent (CRAE); the lowest quintile of CRAE was considered generalized arteriolar narrowing. Of the 1897 women with complete data, 79 (4%) were premenopausal and 315 (17%), 224 (12%), and 1279 (67%) were current, past, and never HRT users, respectively. Among women aged < 65 years, multivariate-adjusted mean CRAE for the four groups was 196, 198, 201, and 200 microm (P < 0.0001), respectively. Among postmenopausal women >/= 65 years, multivariate-adjusted mean CRAE was 187, 188, 191 microm (P < 0.0001), respectively, for current, past, and never users. Current HRT users were 40% more likely than never users to have generalized arteriolar narrowing (95% confidence interval 1.0-2.1). It appears that the use of HRT in older women may not have any long-term vasodilatory effects on retinal arterioles. These data do not support our hypothesis that exogenous estrogen exposures account for observed wider retinal arteriolar diameters in women.     

Losartan and ozagrel reverse retinal arteriolar constriction in non-obese diabetic mice

Objective: Reductions in retinal blood flow are observed early in diabetes. Venules may influence arteriolar constriction and flow; therefore, we hypothesized that diabetes would induce the constriction of arterioles that are in close proximity to venules, with the constriction mediated by thromboxane and angiotensin II. Methods: Using nonobese diabetic (NOD) mice, retinal measurements were performed three weeks following the age at which glucose levels exceeded 200 mg/dL, with accompanying experiments on age‐matched normoglycemic NOD mice. The measurements included retinal arteriolar diameters and red blood cell velocities and were repeated following an injection of the thromboxane synthase inhibitor, ozagrel. Mice were subdivided into equal groups and given drinking water with or without the angiotensin II receptor antagonist, losartan. Results: Retinal arterioles were constricted in hyperglycemic mice, with a significant reduction in flow. However, not all arterioles were equally affected; the vasoconstriction was limited to arterioles that were in closer proximity to venules. The arteriolar vasoconstriction (mean arteriolar diameters = 51 ± 1 vs. 61 ± 1 μ m in controls; p < 0.01) was eliminated by both ozagrel (61 ± 2 μ m) and losartan (63 ± 2 μ m). Conclusions: Venule‐dependent arteriolar vasoconstriction in NOD mice is mediated by thromboxane and/or angiotensin II.     

The relationship of age, blood pressure, serum cholesterol and smoking habits with the risk of typical and atypical coronary heart disease death in the European cohorts of the Seven Countries Study

OBJECTIVE: To explore whether "typical" coronary heart disease (CHD) such as fatal myocardial infarction and sudden death relate to major cardiovascular risk factors in the same way as the "atypical" CHD, such as fatal heart failure and chronic arrhythmias. DESIGN AND SETTING: Ten cohorts (6633 cardiovascular disease-free men, aged 40-59) in five European countries were examined, age and three major risk factors were measured (systolic blood pressure, serum cholesterol, and smoking habits) and 35-year mortality data were collected. Proportional hazard models were solved with typical and atypical CHD deaths treated separately. RESULTS: Death rates from typical and atypical CHD were inversely related among the five countries. Mean age at death was significantly higher for atypical than typical (75.8 versus 71.6 years; p < 0.001). In the multivariate analysis conducted on pools of 5 countries (adjusted for countries), the relationship of risk factors with typical CHD was direct and significant for age (hazard ratio-HR-for 5 years of age 1.44 (95% CI 1.36-1.52)), systolic blood pressure (HR for 20 mm Hg, 1.39 (95% CI 1.32-1.47)), serum cholesterol (HR for 1 mmol/l of 1.22 (95% CI 1.16-1.27)) and smoking habits (HR smokers versus non-smokers of 1.39 (95% CI 1.24-1.57)). For atypical CHD, age had a larger HR of 2.27 (95% CI 2.05-2.52), systolic blood pressure had a smaller HR of 1.28 (95% CI 1.16-1.41), serum cholesterol had an inverse non-significant HR of 0.90 (0.58-1.58) and smoking habits had a larger HR of 1.54 (95% CI 1.26-1.89). CONCLUSIONS: Age and serum cholesterol were differently related with typical and atypical CHD deaths, suggesting different etiologies for these coronary diseases.     

Retinal Arteriolar Diameter and the Prevalence and Incidence of Hypertension: A Systematic Review and Meta-analysis of Their Association

Hypertension is a leading risk factor for increased mortality and morbidity. One pathogenesis mechanism, increased peripheral vascular resistance, relates to arteriolar diameter. Retinal arterioles, visualized and measured through retinal images, provide an insight into the microvascular structure and hints of peripheral vascular resistance. Multiple studies have demonstrated an inverse association between increasing blood pressure and narrowing retinal arteriolar diameter. This systematic review summarizes the currently available evidence from cross-sectional and longitudinal population-based studies that have investigated this association. A meta-analysis of five cross-sectional studies (19,633 adults) provided an averaged regression coefficient of −3.07 μm (95% CI, −3.73, −2.40) narrowing in retinal arteriolar diameter for every 10 mm Hg increase in mean arterial blood pressure. Four longitudinal studies (6,247 adults) with follow-up periods ranging from 3 to 7 years consistently showed that generalized retinal arteriolar narrowing (defined as the lowest tertile, quartile, or quintile in the population) was associated with an increased risk of incident hypertension (meta-analysis odds ratio 1.91; 95% CI, 1.56–2.34).     

Regular aspirin use and retinal microvascular signs: the Blue Mountains Eye Study

OBJECTIVE: Hypertension is closely related to microvascular abnormalities and there is increasing interest in agents that target the microvasculature. The effect of aspirin on the microvasculature has not been well studied. We examined the cross-sectional and longitudinal associations between regular aspirin use and retinal microvascular signs. DESIGN AND METHODS: We digitized retinal photographs from participants of the Blue Mountains Eye Study cohort (1992-1994, n = 3654, aged over 49 years, and 1997-1999, n = 2335) and used a computer-assisted method to measure average retinal arteriolar and venular diameters. Information on the frequency of aspirin use was collected, with regular aspirin use defined as weekly or daily. RESULTS: Regular aspirin users comprised 21.2% (n = 775) of the baseline population. At baseline and in individuals who were on one or more antihypertensive medication, regular aspirin use was found to be associated with retinal arterioles on average 3.6 mum (95% confidence interval 1.0, 6.2) wider than those of non-users or occasional aspirin users, after adjusting for age, blood pressure, smoking, diabetes, non-steroidal anti-inflammatory drug use and other variables. Increasing frequency of aspirin use was associated with increasing retinal arteriolar diameter (Ptrend < 0.01). At 5-year follow-up, regular users of aspirin and antihypertensive medication(s) had wider retinal arterioles than those who used aspirin less regularly. Neither antihypertensive medication use alone nor aspirin use alone was associated with wider retinal vessels. CONCLUSION: Our finding of a possible association between the combined use of aspirin and antihypertensive agent(s) and wider retinal arteriolar diameter warrants further investigation into the effects of aspirin on the microvasculature.     

Ozagrel reverses streptozotocin-induced constriction of arterioles in rat retina

Retinal blood flow decreases early in the progression of diabetic retinopathy; however, the mediators and mechanisms responsible for this decrease have yet to be determined. In this study, diabetes was induced by streptozotocin in rats, and retinal blood flow was measured via intravital microscopy 1 or 3 weeks following the induction of hyperglycemia. Additionally, retinal arteriolar diameters and flow were measured prior to and following acute administration of the thromboxane synthase inhibitor ozagrel to investigate the potential role of thromboxane in the observed constriction. Minimal changes in the retinal diameters and flow were observed at 1 week of diabetes; however, at 3 weeks of diabetes, arteriolar constriction and decreases in blood flow were significant. Notably, the constriction occurred only in the arterioles that were in closer proximity to the venules draining the retina. Acute administration of ozagrel reversed the constriction of the closely venule-paired arterioles. In summary, the results suggest that thromboxane mediates localized, venule-dependent arteriolar constriction induced by streptozotocin-induced diabetes in rats.