IOP and Coronary Artery Calcification in Asymptomatic People
IOP and Coronary Artery Calcification in Asymptomatic People
In this large sample of an asymptomatic population, we found an association between IOP and subclinical atherosclerosis measured by CAC CT. This association remained significant even after adjustment of possible confounders including conventional cardiovascular risk factors.
It is presumed that the increased risk of CAC status and distribution of higher IOP have a coexisting pathophysiology. There is a possibility that high BP would play an important role in both increased IOP and CAC. Elevated BP, an established risk factor for CVD, has been reported to be associated with elevated IOP levels. In our study, SBP, DBP, and hypertension status were positively correlated with higher quartile distribution of IOP. It has been inferred that high BP contributes to the elevation of ciliary artery pressure in the eye, increasing the ultrafiltration and production of aqueous humour. This mechanism has been postulated as the cause of elevated IOP. In this study, however, increasing levels of IOP were progressively associated with the increasing risk of CAC independently of hypertension.
Obesity and other metabolic conditions could be considered for the possible shared pathophysiology between CAC and higher IOP. The result of present study showed increased LDL-C, decreased HDL-C, increased triglycerides, and obesity features based on BMI and waist circumference were associated with higher quartile IOP. Some of these parameters are the main components of metabolic syndrome with elevated BP and fasting glucose value. Metabolic syndrome and obesity are known risk factors of CVD and type 2 diabetes. Several previous studies have also indicated metabolic syndrome as a risk factor for increased IOP or ocular hypertension. However, in this study, the association of IOP with the prevalence of detectable CAC persisted after adjusting further for BMI and metabolic profiles.
Sympathetic neural tone has been proposed as a mechanism for the relationship between heart rate and increased IOP. It was reported, in a rabbit experiment, that the stimulation of the ocular sympathetic nerve could also increase IOP by decreasing aqueous humour outflow. Sympathetic hyperstimulation or dysregulation is well observed in clinical research and suggested as a common physiologic condition of metabolic syndrome, obesity and dyslipidaemia. Therefore, there is a possibility that sympathetic nerve activity could be a link to both CAC and IOP. In regards to obesity and IOP, a hypothesis has been suggested that excessive orbital fatty tissue or lipid deposits are responsible for high episcleral venous pressure and decreased aqueous humour outflow, which results in the elevation of IOP.
Diabetes and glucose tolerance are well known representative risk factors for CVD. Earlier studies documented that diabetes and hyperglycaemia were related to IOP elevation. In our study, interestingly, the association between IOP quartiles and the prevalence of detectable CAC was stronger in diabetic subjects, even though the interaction of IOP quartiles and diabetes for CAC was not statistically significant. The mechanisms by which a higher IOP is more strongly associated with the presence of CAC in diabetic subjects compared to non-diabetic subjects are not fully understood. However, diabetes-related autonomic dysfunction may contribute to increased IOP. Autonomic dysfunction often coexists with other diabetes-related complications including micro- and macrovascular complications. Thus, higher IOP as a manifestation of autonomic dysfunction could coexist with CAC as one of the subclinical macrovascular complications.
Glycation-induced corneal collagen cross-links in diabetes can cause corneal stiffening, which has been shown to increase the level of measured IOP over the true IOP. Studies have found that diabetics have greater central corneal thickness compared to those without the disease, which may artefactually increase IOP readings depending on the IOP measurements. Among diabetic patients, central corneal thickness was significantly correlated with diabetic duration. Thus, artefactually high IOP readings in diabetic patients can reflect longer duration of diabetes, which may relate to the observed association between higher IOP and CAC. Therefore, establishing that higher IOP is associated with increased CAC in diabetic patients will require additional measures to assess further the autonomic dysfunction and relevant ocular factors. Other possibilities may include endothelial dysregulation caused by a hyperglycaemic condition or diabetes. Endothelial dysfunction is a well-explained pathophysiologic model of atherosclerosis in CVD, and many clinical studies have demonstrated the association with diabetes. At the same time, diabetes is one of the main causes that change the microvascular structures and blood flow of the retina, optic nerve head and choroid in the eyes, which lead to diabetic retinopathy and various other eye diseases. One of the MESA (Multi-Ethnic Study of Atherosclerosis) studies found retinopathy is associated with CAC. Many previous studies have also proposed endothelial dysfunction as a contributing mechanism for the progression of glaucoma.
The present research has some limitations. First, the design of this study is a cross-sectional analysis and does not provide a temporal or clear causal relationship between CAC and IOP. Second, the measurement of IOP is based on non-contact air-puff tonometry, and several ocular features, including central corneal thickness and corneal rigidity, were not considered in this study. However, only obtaining the IOP is acceptable and widely used in health screening centres to reduce the time for estimation. Generally, large scale cohort or population based studies usually use a non-contact tonometer to measure IOP. Several previous studies such as the Beijing Eye Study in China, the Shihpai Eye Study in Taiwan, and the Gutenberg Health Study in Germany used non-contact air puff devices. Although this method does not evaluate the ocular characteristics associated with IOP, we measured the IOP in both eyes of all the participants twice and measurements within 2 mm Hg of one another were used for more accurate and proper analysis. Finally, our study population consisted of young to middle-aged Korean men and women, and the findings may not be generalisable to other populations.
In conclusion, this is the first study to evaluate the association between the risk of subclinical coronary atherosclerosis and IOP, demonstrating that the presence of CAC is associated with higher IOP. The present study provides more insight into understanding the process of subclinical atherosclerosis in CVD and the relationship with higher IOP as a common pathophysiology.
Discussion
In this large sample of an asymptomatic population, we found an association between IOP and subclinical atherosclerosis measured by CAC CT. This association remained significant even after adjustment of possible confounders including conventional cardiovascular risk factors.
It is presumed that the increased risk of CAC status and distribution of higher IOP have a coexisting pathophysiology. There is a possibility that high BP would play an important role in both increased IOP and CAC. Elevated BP, an established risk factor for CVD, has been reported to be associated with elevated IOP levels. In our study, SBP, DBP, and hypertension status were positively correlated with higher quartile distribution of IOP. It has been inferred that high BP contributes to the elevation of ciliary artery pressure in the eye, increasing the ultrafiltration and production of aqueous humour. This mechanism has been postulated as the cause of elevated IOP. In this study, however, increasing levels of IOP were progressively associated with the increasing risk of CAC independently of hypertension.
Obesity and other metabolic conditions could be considered for the possible shared pathophysiology between CAC and higher IOP. The result of present study showed increased LDL-C, decreased HDL-C, increased triglycerides, and obesity features based on BMI and waist circumference were associated with higher quartile IOP. Some of these parameters are the main components of metabolic syndrome with elevated BP and fasting glucose value. Metabolic syndrome and obesity are known risk factors of CVD and type 2 diabetes. Several previous studies have also indicated metabolic syndrome as a risk factor for increased IOP or ocular hypertension. However, in this study, the association of IOP with the prevalence of detectable CAC persisted after adjusting further for BMI and metabolic profiles.
Sympathetic neural tone has been proposed as a mechanism for the relationship between heart rate and increased IOP. It was reported, in a rabbit experiment, that the stimulation of the ocular sympathetic nerve could also increase IOP by decreasing aqueous humour outflow. Sympathetic hyperstimulation or dysregulation is well observed in clinical research and suggested as a common physiologic condition of metabolic syndrome, obesity and dyslipidaemia. Therefore, there is a possibility that sympathetic nerve activity could be a link to both CAC and IOP. In regards to obesity and IOP, a hypothesis has been suggested that excessive orbital fatty tissue or lipid deposits are responsible for high episcleral venous pressure and decreased aqueous humour outflow, which results in the elevation of IOP.
Diabetes and glucose tolerance are well known representative risk factors for CVD. Earlier studies documented that diabetes and hyperglycaemia were related to IOP elevation. In our study, interestingly, the association between IOP quartiles and the prevalence of detectable CAC was stronger in diabetic subjects, even though the interaction of IOP quartiles and diabetes for CAC was not statistically significant. The mechanisms by which a higher IOP is more strongly associated with the presence of CAC in diabetic subjects compared to non-diabetic subjects are not fully understood. However, diabetes-related autonomic dysfunction may contribute to increased IOP. Autonomic dysfunction often coexists with other diabetes-related complications including micro- and macrovascular complications. Thus, higher IOP as a manifestation of autonomic dysfunction could coexist with CAC as one of the subclinical macrovascular complications.
Glycation-induced corneal collagen cross-links in diabetes can cause corneal stiffening, which has been shown to increase the level of measured IOP over the true IOP. Studies have found that diabetics have greater central corneal thickness compared to those without the disease, which may artefactually increase IOP readings depending on the IOP measurements. Among diabetic patients, central corneal thickness was significantly correlated with diabetic duration. Thus, artefactually high IOP readings in diabetic patients can reflect longer duration of diabetes, which may relate to the observed association between higher IOP and CAC. Therefore, establishing that higher IOP is associated with increased CAC in diabetic patients will require additional measures to assess further the autonomic dysfunction and relevant ocular factors. Other possibilities may include endothelial dysregulation caused by a hyperglycaemic condition or diabetes. Endothelial dysfunction is a well-explained pathophysiologic model of atherosclerosis in CVD, and many clinical studies have demonstrated the association with diabetes. At the same time, diabetes is one of the main causes that change the microvascular structures and blood flow of the retina, optic nerve head and choroid in the eyes, which lead to diabetic retinopathy and various other eye diseases. One of the MESA (Multi-Ethnic Study of Atherosclerosis) studies found retinopathy is associated with CAC. Many previous studies have also proposed endothelial dysfunction as a contributing mechanism for the progression of glaucoma.
The present research has some limitations. First, the design of this study is a cross-sectional analysis and does not provide a temporal or clear causal relationship between CAC and IOP. Second, the measurement of IOP is based on non-contact air-puff tonometry, and several ocular features, including central corneal thickness and corneal rigidity, were not considered in this study. However, only obtaining the IOP is acceptable and widely used in health screening centres to reduce the time for estimation. Generally, large scale cohort or population based studies usually use a non-contact tonometer to measure IOP. Several previous studies such as the Beijing Eye Study in China, the Shihpai Eye Study in Taiwan, and the Gutenberg Health Study in Germany used non-contact air puff devices. Although this method does not evaluate the ocular characteristics associated with IOP, we measured the IOP in both eyes of all the participants twice and measurements within 2 mm Hg of one another were used for more accurate and proper analysis. Finally, our study population consisted of young to middle-aged Korean men and women, and the findings may not be generalisable to other populations.
In conclusion, this is the first study to evaluate the association between the risk of subclinical coronary atherosclerosis and IOP, demonstrating that the presence of CAC is associated with higher IOP. The present study provides more insight into understanding the process of subclinical atherosclerosis in CVD and the relationship with higher IOP as a common pathophysiology.