ABSTRACT
OBJECTIVE: Morphological change in retinal vessel calibers has been reported as a marker of cardiovascular risk, but its association with arterial stiffening, a possible factor relating retinal vessel sings and cardiovascular outcomes, is not clear. The study aim was to clarify the relationship between retinal small vessel calibers and longitudinal change in large arterial stiffness in a sample of the general population. METHODS: The study included 6720 Japanese participants (52.1â±â12.8 years). Central retinal arteriolar equivalent (CRAE) and venular equivalent were measured by fundus photography. Arterial stiffness was evaluated by brachial-to-ankle pulse wave velocity (baPWV) at baseline and at 5 years. RESULTS: The overall change in baPWV (ΔbaPWV) during a mean follow-up 1814â±â136 days was 41â±â131âcm/s (3.4â±â9.9%), and was significantly increased in individuals with narrower CRAE (quartiles: Q1, 4.3â±â10.6%; Q2, 3.3â±â10.0%; Q3, 3.1â±â9.3%; Q4, 3.1â±â9.7%, Pâ=â0.001). No significant association was observed with central retinal venular equivalent. Multivariate analysis identified CRAE as a significant inverse determinant of ΔbaPWV (ßâ=â-0.033, Pâ=â0.006) independent of possible covariates including age, sex, blood pressure, and baseline baPWV. The association between CRAE and ΔbaPWV was prominent in a middle-aged (age Q2, ßâ=â-0.078, Pâ=â0.002), but not younger (Q1, Pâ=â0.232) or older (Q3, Pâ=â0.427; Q4, Pâ=â0.542) participants. CONCLUSION: Narrower CRAE in middle-age was associated with the long-term risk of arteriosclerosis in a general population sample.
Subject(s)
Arteries/physiology , Retinal Vessels/anatomy & histology , Vascular Stiffness/physiology , Adult , Aged , Arteries/physiopathology , Arterioles/anatomy & histology , Blood Pressure/physiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Multivariate Analysis , Pulse Wave Analysis , Retinal Vessels/physiologyABSTRACT
Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10-5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10-9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10-7 and 9.73 × 10-7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.
