Fractal analysis of retinal microvasculature and coronary heart disease mortality.

AIM Fractal analysis provides a global assessment of vascular network architecture. We examined the relationship of retinal vascular fractal dimension (D(f)) with coronary heart disease (CHD) mortality. METHODS AND RESULTS We examined the relationship of D(f) with 14-year CHD mortality in a prospective, population-based cohort of 3303 participants aged 49 years or older. D(f) was measured from digitized fundus photographs using computer-automated methods; CHD mortality was documented from Australian National Death Index records. Mean D(f) in this population was 1.441 (standard deviation, 0.024). Over 14 years, there were 468 (14.2%) CHD deaths. Participants with suboptimal D(f) (lowest and highest quartiles) had 50% higher 14-year CHD mortality than those with optimal D(f) (middle quartiles), after adjusting for age, blood pressure, and other risk factors. Among participants aged ≤ 70 years, suboptimal D(f) was associated with a nearly two-fold higher risk of CHD mortality [adjusted hazard ratio (HR) 1.89, 95% confidence interval (CI), 1.25, 2.84 for the lowest quartile and HR 1.87, CI 1.30, 2.69 for the highest quartile, compared with middle quartiles]. CONCLUSIONS D(f) is a novel means of quantifying microvascular branching that independently predicted 14-year CHD mortality. These findings suggest that suboptimal microvascular branching may play a role in development of clinical cardiovascular disease.

[1]  I. Deary,et al.  Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures , 2005, Journal of anatomy.

[2]  C. Matula,et al.  Correlation of microvascular fractal dimension with positron emission tomography [(11)C]-methionine uptake in glioblastoma multiforme: preliminary findings. , 2010, Microvascular research.

[3]  R. Cannon,et al.  Impaired forearm vasodilator reserve in patients with microvascular angina. Evidence of a generalized disorder of vascular function? , 1987, The New England journal of medicine.

[4]  J M Wardlaw,et al.  Fractal analysis of retinal vessels suggests that a distinct vasculopathy causes lacunar stroke , 2010, Neurology.

[5]  N. Chapman,et al.  Peripheral vascular disease is associated with abnormal arteriolar diameter relationships at bifurcations in the human retina. , 2002, Clinical science.

[6]  Sun Ha Jee,et al.  Body-mass index and mortality in Korean men and women. , 2006, The New England journal of medicine.

[7]  Tatijana Stosic,et al.  Multifractal analysis of human retinal vessels , 2006, IEEE Transactions on Medical Imaging.

[8]  P. Mitchell,et al.  Retinal Vascular Imaging: A New Tool in Microvascular Disease Research , 2008, Circulation. Cardiovascular imaging.

[9]  A. Popel,et al.  The cost of departure from optimal radii in microvascular networks. , 1989, Journal of theoretical biology.

[10]  A L Goldberger,et al.  Fractal correlation properties of R-R interval dynamics and mortality in patients with depressed left ventricular function after an acute myocardial infarction. , 2000, Circulation.

[11]  R. Klein,et al.  Abnormalities of Retinal Microvascular Structure and Risk of Mortality From Ischemic Heart Disease and Stroke , 2006, Hypertension.

[12]  Neil Chapman,et al.  Quantification of topological changes in retinal vascular architecture in essential and malignant hypertension , 2006, Journal of hypertension.

[13]  T. Wong,et al.  Fractal analysis of the retinal vasculature and chronic kidney disease. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  B. Wasan,et al.  Vascular network changes in the retina with age and hypertension , 1995, Journal of hypertension.

[15]  S. Rossitti,et al.  Optimality Principles and Flow Orderliness at the Branching Points of Cerebral Arteries , 1993, Stroke.

[16]  P. Mitchell,et al.  Evidence of Arteriolar Narrowing in Low-Birth-Weight Children , 2008, Circulation.

[17]  M Zamir,et al.  Branching characteristics of human coronary arteries. , 1986, Canadian journal of physiology and pharmacology.

[18]  P D Esser,et al.  Fractal Analysis of Pulmonary Arteries: The Fractal Dimension Is Lower in Pulmonary Hypertension , 1994, Journal of thoracic imaging.

[19]  Ian J. Deary,et al.  Retinal image analysis: concepts, applications and potential , 2006 .

[20]  T. N. James,et al.  The spectrum of diseases of small coronary arteries and their physiologic consequences. , 1990, Journal of the American College of Cardiology.

[21]  Konrad Jamrozik.  Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies , 2002 .

[22]  R. Klein,et al.  Retinal arteriolar narrowing and left ventricular remodeling: the multi-ethnic study of atherosclerosis. , 2007, Journal of the American College of Cardiology.

[23]  P. Mitchell,et al.  The retinal vasculature as a fractal: methodology, reliability, and relationship to blood pressure. , 2008, Ophthalmology.

[24]  C Cherniak,et al.  Modeling the large-scale geometry of human coronary arteries. , 2000, Canadian journal of physiology and pharmacology.

[25]  R. Klein,et al.  Meta-analysis: Retinal Vessel Caliber and Risk for Coronary Heart Disease , 2009, Annals of Internal Medicine.

[26]  R. Klein,et al.  Retinal Vascular Caliber and Brachial Flow-Mediated Dilation: The Multi-Ethnic Study of Atherosclerosis , 2010, Stroke.

[27]  Terri L. McKay,et al.  Selective inhibition of angiogenesis in small blood vessels and decrease in vessel diameter throughout the vascular tree by triamcinolone acetonide. , 2008, Investigative ophthalmology & visual science.

[28]  Tien Y Wong,et al.  Hypertensive retinopathy. , 2004, The New England journal of medicine.

[29]  J. J. Wang,et al.  Retinal vascular calibre and the risk of coronary heart disease-related death , 2006, Heart.

[30]  R. Klein,et al.  Relationship Between Retinal Arteriolar Narrowing and Myocardial Perfusion: Multi-Ethnic Study of Atherosclerosis , 2008, Hypertension.

[31]  T. Seppänen,et al.  Physiological Background of the Loss of Fractal Heart Rate Dynamics , 2005, Circulation.

[32]  Silvia Schievano,et al.  Fractal Dimension: A Novel Method of Quantifying Vascular Structural Changes in Pulmonary Hypertension , 2009 .

[33]  R. Klein,et al.  Retinal vessel diameter and cardiovascular mortality: pooled data analysis from two older populations. , 2007, European heart journal.

[34]  B. Masters,et al.  Fractal analysis of the vascular tree in the human retina. , 2004, Annual review of biomedical engineering.

[35]  Paul Mitchell,et al.  Retinal fractals and acute lacunar stroke , 2010, Annals of neurology.

[36]  J. Shaw,et al.  Correlation of light-flicker-induced retinal vasodilation and retinal vascular caliber measurements in diabetes. , 2009, Investigative ophthalmology & visual science.

[37]  Oscar L Lopez,et al.  Fractal analysis of retinal vessels , 2010, Neurology.

[38]  C. Sparrow.  The Fractal Geometry of Nature , 1984 .

[39]  C D Murray,et al.  The Physiological Principle of Minimum Work: I. The Vascular System and the Cost of Blood Volume. , 1926, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Fractals and medicine , 1991, The Lancet.

[41]  Paul Mitchell,et al.  The eye in hypertension , 2007, The Lancet.

[42]  M Zamir,et al.  Cost analysis of arterial branching in the cardiovascular systems of man and animals. , 1986, Journal of theoretical biology.

[43]  P. Luzi,et al.  Fractal analysis of fluoroangiographic patterns in anterior ischaemic optic neuropathy and optic neuritis: a pilot study , 2008, Clinical & experimental ophthalmology.

[44]  A. Daxer.  Characterisation of the neovascularisation process in diabetic retinopathy by means of fractal geometry: diagnostic implications , 1993, Graefe's Archive for Clinical and Experimental Ophthalmology.

[45]  A. Tonkin,et al.  Accuracy of the Australian National Death Index: comparison with adjudicated fatal outcomes among Australian participants in the Long‐term Intervention with Pravastatin in Ischaemic Disease (LIPID) study , 2003, Australian and New Zealand journal of public health.

[46]  Tien Yin Wong,et al.  Retinal vascular fractals and microvascular and macrovascular complications in type 1 diabetes. , 2010, Ophthalmology.

[47]  T. Wong,et al.  Quantitative Assessment of Early Diabetic Retinopathy Using Fractal Analysis , 2009, Diabetes Care.

[48]  Filippo Crea,et al.  Coronary microvascular dysfunction. , 2013, The New England journal of medicine.

[49]  T. MacGillivray,et al.  Fractal analysis of the retinal vascular network in fundus images , 2007, 2007 29th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[50]  Alberto Porta,et al.  Different spectral components of 24 h heart rate variability are related to different modes of death in chronic heart failure. , 2005, European heart journal.