Prospective cohort study of retinal vessel diameters and risk of hypertension
http://www.100md.com
《英国医生杂志》
1 Centre for Eye Research Australia, University of Melbourne, Victoria 3002, Australia, 2 Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin 53726, USA, 3 Fundus Photograph Reading Centre, University of Wisconsin, Madison
Correspondence to: T Wong twong@unimelb.edu.au
Abstract
Contemporary guidelines for the treatment of hypertension are based on an empirical approach to lowering blood pressure, with less emphasis on specific antihypertensive treatment.1 In part, this is because of uncertainty about the basic pathophysiological mechanisms of essential hypertension.2
A key pathological characteristic of hypertension is the presence of small vessel disease, specifically vasoconstriction and narrowing of the peripheral small arteries and arterioles.3-7 Narrowing of these arterioles may contribute to the pathogenesis of hypertension by increasing peripheral vascular resistance. However, it is unclear whether arteriolar narrowing precedes development of hypertension or is merely a physiological response of raised blood pressure.8 There have been no long term prospective data showing a link between arteriolar narrowing and the subsequent risk of hypertension.8
Measurement of the retinal arterioles offers a non-invasive means to evaluate systemic associations of the human microcirculation in vivo. We have recently developed a computer based method to measure retinal arterioles and venules from photographic images.9 We examined the prospective association between retinal arteriolar diameters and the 10 year incidence of hypertension in a population based cohort of normotensive people.
Methods
Table 1 shows baseline characteristics of participants, according to arteriole:venule ratio. Lower arteriole:venule ratios were associated with older age, male sex, diabetes, higher glycosylated haemoglobin concentration, higher systolic and diastolic blood pressure, higher body mass index, higher total cholesterol concentration, lower high density lipoprotein cholesterol concentration, cigarette smoking, and alcohol consumption.
Table 1 Baseline characteristics of study population in relation to retinal arteriole:venule ratio. Figures are means unless stated otherwise
Over the 10 year period 721 people developed hypertension. After adjustment for age and sex, those who developed incident hypertension had significantly lower mean baseline arteriole:venule ratio (0.69 v 0.72, P < 0.001) and smaller retinal arteriolar diameter (166.0 μm v 172.5 μm, P < 0.001) compared with those who did not develop hypertension. In contrast, baseline retinal venular diameter was similar in participants who did and did not develop hypertension (241.0 μm v 241.7 μm, P = 0.17).
Table 2 shows the incidence and odds ratio for incident hypertension in relation to the retinal arteriole:venule ratio. After we controlled for age and sex, participants with an arteriole:venule ratio in the first (lowest) quarter were three times as likely to develop hypertension than those with a ratio in the fourth quarter (odds ratio 2.95, 95% confidence interval 2.27 to 3.85). Further adjustment for risk factors associated with hypertension had minimal impact on this association (2.72, 2.08 to 3.54). This association was attenuated but remained significant even after further adjustment for baseline systolic and diastolic blood pressure and pulse pressure (1.82, 1.39 to 2.40). The pattern of association for retinal arteriolar diameter was essentially similar to that of the arteriole:venule ratio, but retinal venular diameter was unrelated to incident hypertension (see table A on bmj.com).
Table 2 Odds ratio (95% confidence interval) for incident hypertension in relation to retinal arteriole:venule ratio
When we stratified data according to baseline blood pressure, participants who were classified as "pre-hypertensive" and who had lower arteriole:venule ratios were more likely to develop hypertension than people with "normal" baseline blood pressure and higher arteriole:venule ratio (fig 2).
Fig 2 Odds ratios for incident hypertension associated with baseline blood pressure (normal, prehypertensive) and arteriole:venule ratio quarters, adjusted for variables listed in table 3. Reference group (REF) is normal blood pressure and fourth (highest) quarter of arteriole:venule ratio
Table 3 Odds ratio (95% confidence interval) for incident hypertension per SD decrease in retinal arteriole:venule ratio, stratified by risk factors
When we analysed the arteriole:venule ratio as a continuous variable, each SD decrease (a decrease of 0.07) was associated with a 30% increase in odds of hypertension (table 3). We examined for possible interaction with sex and other risk factors for hypertension (diabetes, body mass index, waist:hip ratio, cigarette smoking, and alcohol consumption) by stratification (table 3) and by inclusion of cross product terms in the logistic regression models. We did not find significant interactions (all cross product terms P > 0.20).
Finally, we constructed multiple linear regression models of retinal arteriole:venule ratio and change in blood pressure between baseline and the 10 year follow up. After we excluded participants taking antihypertensive medications at the follow up examinations, baseline retinal arteriole:venule ratio was inversely associated with a 10 year change in blood pressure (see table B on bmj.com). When we included the blood pressures of those who were taking antihypertensive medications at the follow up examinations, the magnitude of this inverse association was attenuated, as expected, but remained significant (P < 0.05).
Discusssion
Mulrow CD, Pignone M. What are the elements of good treatment for hypertension? BMJ 2001;322: 1107-9.
Beevers G, Lip GY, O'Brien E. ABC of hypertension: the pathophysiology of hypertension. BMJ 2001;322: 912-6.
Folkow B. Physiological aspects of primary hypertension. Physiol Rev 1982;62: 347-504.
Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev 1990;70: 921-61.
Rizzoni D, Castellano M, Porteri E, Bettoni G, Muiesan ML, Agabiti-Rosei E. Vascular structural and functional alterations before and after the development of hypertension in SHR. Am J Hypertens 1994;7: 193-200.
Norrelund H, Christensen KL, Samani NJ, Kimber P, Mulvany MJ, Korsgaard N. Early narrowed afferent arteriole is a contributor to the development of hypertension. Hypertension 1994;24: 301-8.
Mulvany MJ, Baumbach GL, Aalkjaer C, Heagerty AM, Korsgaard N, Schiffrin EL, et al. Vascular remodeling. Hypertension 1996;28: 505-6.
Mulvany MJ. Are vascular abnormalities a primary cause or secondary consequence of hypertension? Hypertension 1991;18(3 suppl): I52-7.
Hubbard LD, Brothers RJ, King WN, Clegg LX, Klein R, Cooper LS, et al. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities (ARIC) study. Ophthalmology 1999;106: 2269-80.
Klein R, Klein BEK, Linton KLP, DeMets DL. The Beaver Dam eye study: visual acuity. Ophthalmology 1991;98: 1310-5.
Klein R, Klein BEK, Lee KE. The changes in visual acuity in a population. The Beaver Dam eye study. Ophthalmology 1996;103: 1169-78.
Klein R, Klein BE, Lee KE, Cruickshanks KJ, Chappell RJ. Changes in visual acuity in a population over a 10-year period: the Beaver Dam eye study. Ophthalmology. 2001;108: 1757-66.
Wong TY, Klein R, Klein BEK, Meuer SM, Hubbard LD. Retinal vessel diameters and their associations with age and blood pressure. Invest Ophthalmol Vis Sci 2003;44: 4644-50.
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BEK. A revised method for summarizing retinal vessel diameters. Curr Eye Res 2003;27: 143-9.
Klein R, Klein BEK. Beaver Dam eye study. Manual of operations. Springfield, VA: Department of Ophthalmology, University of Wisconsin-Madison, 1991. (NTIS Accession No. PB 91-149823.)
Hypertension Detection and Follow-up Program Cooperative Group. The hypertension detection and follow-up program. Prev Med 1976;5: 207-15.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003;289: 2560-71.
Tso MOM, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthalmology 1982;89: 1132-45.
Klein R, Sharrett AR, Klein BE, Chambless LE, Cooper LS, Hubbard LD, et al. Are retinal arteriolar abnormalities related to atherosclerosis? The atherosclerosis risk in communities study. Arterioscler Thromb Vasc Biol 2000;20: 1644-50.
Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Klein BEK. Retinal arteriolar diameters and risk of hypertension. Ann Intern Med 2004;140: 248-55.
Pries AR, Secomb TW, Gaehtgens P. Structural autoregulation of terminal vascular beds: vascular adaptation and development of hypertension. Hypertension 1999;33: 153-61.
Thybo NK, Stephens N, Cooper A, Aalkjaer C, Heagerty AM, Mulvany MJ, et al. Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995;25: 474-81.
Rizzoni D, Porteri E, Boari GE, De Ciuceis C, Sleiman I, Muiesan ML, et al. Prognostic significance of small-artery structure in hypertension. Circulation 2003;108: 2230-5.
Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HA. Microcirculation in hypertension: a new target for treatment? Circulation 2001;104: 735-40.(Tien Yin Wong, associate )
Correspondence to: T Wong twong@unimelb.edu.au
Abstract
Contemporary guidelines for the treatment of hypertension are based on an empirical approach to lowering blood pressure, with less emphasis on specific antihypertensive treatment.1 In part, this is because of uncertainty about the basic pathophysiological mechanisms of essential hypertension.2
A key pathological characteristic of hypertension is the presence of small vessel disease, specifically vasoconstriction and narrowing of the peripheral small arteries and arterioles.3-7 Narrowing of these arterioles may contribute to the pathogenesis of hypertension by increasing peripheral vascular resistance. However, it is unclear whether arteriolar narrowing precedes development of hypertension or is merely a physiological response of raised blood pressure.8 There have been no long term prospective data showing a link between arteriolar narrowing and the subsequent risk of hypertension.8
Measurement of the retinal arterioles offers a non-invasive means to evaluate systemic associations of the human microcirculation in vivo. We have recently developed a computer based method to measure retinal arterioles and venules from photographic images.9 We examined the prospective association between retinal arteriolar diameters and the 10 year incidence of hypertension in a population based cohort of normotensive people.
Methods
Table 1 shows baseline characteristics of participants, according to arteriole:venule ratio. Lower arteriole:venule ratios were associated with older age, male sex, diabetes, higher glycosylated haemoglobin concentration, higher systolic and diastolic blood pressure, higher body mass index, higher total cholesterol concentration, lower high density lipoprotein cholesterol concentration, cigarette smoking, and alcohol consumption.
Table 1 Baseline characteristics of study population in relation to retinal arteriole:venule ratio. Figures are means unless stated otherwise
Over the 10 year period 721 people developed hypertension. After adjustment for age and sex, those who developed incident hypertension had significantly lower mean baseline arteriole:venule ratio (0.69 v 0.72, P < 0.001) and smaller retinal arteriolar diameter (166.0 μm v 172.5 μm, P < 0.001) compared with those who did not develop hypertension. In contrast, baseline retinal venular diameter was similar in participants who did and did not develop hypertension (241.0 μm v 241.7 μm, P = 0.17).
Table 2 shows the incidence and odds ratio for incident hypertension in relation to the retinal arteriole:venule ratio. After we controlled for age and sex, participants with an arteriole:venule ratio in the first (lowest) quarter were three times as likely to develop hypertension than those with a ratio in the fourth quarter (odds ratio 2.95, 95% confidence interval 2.27 to 3.85). Further adjustment for risk factors associated with hypertension had minimal impact on this association (2.72, 2.08 to 3.54). This association was attenuated but remained significant even after further adjustment for baseline systolic and diastolic blood pressure and pulse pressure (1.82, 1.39 to 2.40). The pattern of association for retinal arteriolar diameter was essentially similar to that of the arteriole:venule ratio, but retinal venular diameter was unrelated to incident hypertension (see table A on bmj.com).
Table 2 Odds ratio (95% confidence interval) for incident hypertension in relation to retinal arteriole:venule ratio
When we stratified data according to baseline blood pressure, participants who were classified as "pre-hypertensive" and who had lower arteriole:venule ratios were more likely to develop hypertension than people with "normal" baseline blood pressure and higher arteriole:venule ratio (fig 2).
Fig 2 Odds ratios for incident hypertension associated with baseline blood pressure (normal, prehypertensive) and arteriole:venule ratio quarters, adjusted for variables listed in table 3. Reference group (REF) is normal blood pressure and fourth (highest) quarter of arteriole:venule ratio
Table 3 Odds ratio (95% confidence interval) for incident hypertension per SD decrease in retinal arteriole:venule ratio, stratified by risk factors
When we analysed the arteriole:venule ratio as a continuous variable, each SD decrease (a decrease of 0.07) was associated with a 30% increase in odds of hypertension (table 3). We examined for possible interaction with sex and other risk factors for hypertension (diabetes, body mass index, waist:hip ratio, cigarette smoking, and alcohol consumption) by stratification (table 3) and by inclusion of cross product terms in the logistic regression models. We did not find significant interactions (all cross product terms P > 0.20).
Finally, we constructed multiple linear regression models of retinal arteriole:venule ratio and change in blood pressure between baseline and the 10 year follow up. After we excluded participants taking antihypertensive medications at the follow up examinations, baseline retinal arteriole:venule ratio was inversely associated with a 10 year change in blood pressure (see table B on bmj.com). When we included the blood pressures of those who were taking antihypertensive medications at the follow up examinations, the magnitude of this inverse association was attenuated, as expected, but remained significant (P < 0.05).
Discusssion
Mulrow CD, Pignone M. What are the elements of good treatment for hypertension? BMJ 2001;322: 1107-9.
Beevers G, Lip GY, O'Brien E. ABC of hypertension: the pathophysiology of hypertension. BMJ 2001;322: 912-6.
Folkow B. Physiological aspects of primary hypertension. Physiol Rev 1982;62: 347-504.
Mulvany MJ, Aalkjaer C. Structure and function of small arteries. Physiol Rev 1990;70: 921-61.
Rizzoni D, Castellano M, Porteri E, Bettoni G, Muiesan ML, Agabiti-Rosei E. Vascular structural and functional alterations before and after the development of hypertension in SHR. Am J Hypertens 1994;7: 193-200.
Norrelund H, Christensen KL, Samani NJ, Kimber P, Mulvany MJ, Korsgaard N. Early narrowed afferent arteriole is a contributor to the development of hypertension. Hypertension 1994;24: 301-8.
Mulvany MJ, Baumbach GL, Aalkjaer C, Heagerty AM, Korsgaard N, Schiffrin EL, et al. Vascular remodeling. Hypertension 1996;28: 505-6.
Mulvany MJ. Are vascular abnormalities a primary cause or secondary consequence of hypertension? Hypertension 1991;18(3 suppl): I52-7.
Hubbard LD, Brothers RJ, King WN, Clegg LX, Klein R, Cooper LS, et al. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities (ARIC) study. Ophthalmology 1999;106: 2269-80.
Klein R, Klein BEK, Linton KLP, DeMets DL. The Beaver Dam eye study: visual acuity. Ophthalmology 1991;98: 1310-5.
Klein R, Klein BEK, Lee KE. The changes in visual acuity in a population. The Beaver Dam eye study. Ophthalmology 1996;103: 1169-78.
Klein R, Klein BE, Lee KE, Cruickshanks KJ, Chappell RJ. Changes in visual acuity in a population over a 10-year period: the Beaver Dam eye study. Ophthalmology. 2001;108: 1757-66.
Wong TY, Klein R, Klein BEK, Meuer SM, Hubbard LD. Retinal vessel diameters and their associations with age and blood pressure. Invest Ophthalmol Vis Sci 2003;44: 4644-50.
Knudtson MD, Lee KE, Hubbard LD, Wong TY, Klein R, Klein BEK. A revised method for summarizing retinal vessel diameters. Curr Eye Res 2003;27: 143-9.
Klein R, Klein BEK. Beaver Dam eye study. Manual of operations. Springfield, VA: Department of Ophthalmology, University of Wisconsin-Madison, 1991. (NTIS Accession No. PB 91-149823.)
Hypertension Detection and Follow-up Program Cooperative Group. The hypertension detection and follow-up program. Prev Med 1976;5: 207-15.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003;289: 2560-71.
Tso MOM, Jampol LM. Pathophysiology of hypertensive retinopathy. Ophthalmology 1982;89: 1132-45.
Klein R, Sharrett AR, Klein BE, Chambless LE, Cooper LS, Hubbard LD, et al. Are retinal arteriolar abnormalities related to atherosclerosis? The atherosclerosis risk in communities study. Arterioscler Thromb Vasc Biol 2000;20: 1644-50.
Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Klein BEK. Retinal arteriolar diameters and risk of hypertension. Ann Intern Med 2004;140: 248-55.
Pries AR, Secomb TW, Gaehtgens P. Structural autoregulation of terminal vascular beds: vascular adaptation and development of hypertension. Hypertension 1999;33: 153-61.
Thybo NK, Stephens N, Cooper A, Aalkjaer C, Heagerty AM, Mulvany MJ, et al. Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension. Hypertension 1995;25: 474-81.
Rizzoni D, Porteri E, Boari GE, De Ciuceis C, Sleiman I, Muiesan ML, et al. Prognostic significance of small-artery structure in hypertension. Circulation 2003;108: 2230-5.
Levy BI, Ambrosio G, Pries AR, Struijker-Boudier HA. Microcirculation in hypertension: a new target for treatment? Circulation 2001;104: 735-40.(Tien Yin Wong, associate )