Cardiovascular Risk Management in Ankylosing Spondylitis
Cardiovascular Risk Management in Ankylosing Spondylitis
In this observational cohort study we observed increased rates of hypertension and smoking in patients with active AS when compared to the general Dutch background population. This observation together with a documented elevated CV risk in AS patients emphasizes the need for optimal CV-RM. The majority of patients at increased CV risk received treatment, but CV-RM remains an important challenge for treating physicians, as treatment targets were often not achieved.
Available studies of the prevalence of CV risk factors in AS patients yield varying results. These differences could be explained by the heterogeneity of study populations investigated. Given the close relationship between inflammation, CV risk factors, and CV risk, we choose to assess CV risk and its risk factors in AS patients with high disease activity. In this selected population, we observed higher prevalence rates of hypertension and smoking, but not hypercholesterolemia and overweight. Inflammation may deteriorate CV risk factors, but patients with active disease may also experience more pain and physical stiffness, which can induce physical inactivity, increasing the chance of overweight and hypertension. The common use of NSAIDs might also contribute to the increased prevalence of hypertension. In fact, although the blood pressure was not significantly different, anti-hypertensive agents were prescribed significantly more in AS patients on NSAIDs.
The number of patients at high CV risk varied widely depending on the CV risk algorithm that was used. According to the Dutch CV-RM guidelines, 7% of assessed AS patients was at high CV risk, while 22% and 29% were at high risk according to either the European or American CV-RM guidelines. Overall, 5% of AS patients was at high CV risk according to all three guidelines. The large variation between the different CV-RM guidelines is remarkable. Several factors can explain this variation. First, the clinical outcomes on which the different guidelines are based vary from 10-years CV risk to develop a fatal atherosclerotic CV event (European CV-RM guidelines), 10-years CV risk to develop a fatal or non-fatal myocardial infarction or stroke (2013 ACC/AHA guidelines), or to 10-years CV risk to develop a fatal or non-fatal atherosclerotic event (Dutch CV-RM guidelines). Second, all guidelines are applicable for different age categories, i.e. Dutch for 40–70, European for 40–65, and ACC/AHA for 40–79 years of age.
To date, it is recognized that systemic inflammation is an important CV risk factor. However, none of the CV-RM guidelines adjust for the inflammatory burden in AS patients, which could lead to underestimation of CV risk. The EULAR task force advised to use a multiplication factor of 1.5 to CV risk to adjust for the increased CV risk in RA when patients have a disease duration >10 years, rheumatoid factor or anti-cyclic citrullinated peptide positivity, or presence of extra-articular manifestations. The Dutch CV-RM guidelines add 15 years to the age of all RA patients to calculate CV risk, as is also applied in DM patients. Currently, due to lack of evidence, it is unknown if, and if yes, what modification factor for CV risk assessment in AS patients is most appropriate. To investigate the impact of a modification factor for the increased CV risk in AS patients, we used the same modification factors as used in RA, for our group of AS patients. When adding 15 years to the age of the AS patients in this cohort, the percentage of patients with high CV risk increases from 7% to 26%. Subsequently, undertreatment of this CV risk increased from 28% to 44%. Future studies should be conducted to investigate which CV risk stratification method most accurately predicts CV risk in AS patients.
Since most patients with AS die from complications of atherosclerosis, early identification and optimal CV-RM is of utmost importance. It is reassuring that the awareness of CV-RM was good, as the vast majority of AS patients at risk for CV disease received treatment. However, it is alarming to see that in 76% CV-RM was suboptimal, as treatment targets were not reached. Moreover, in none of AS patients needing secondary prevention of CV disease, treatment targets were reached. Undertreatment of CV risk (factors) can be caused by multiple factors. First, there might be a lack of awareness of the increased CV risk in AS patients in treating physicians. Second, CV-RM, including CV risk screening, treatment, and follow-up, is time consuming and lack of time to act on guidelines presents an additional hurdle. Also, it is not clear who has responsibility for CV-RM in AS patients, as this can be the primary care physician, the treating rheumatologist, or both. The number and complexity of available guidelines also impede their implementation. Finally, since AS is often diagnosed early in life, implementing a lifetime treatment with medication for CV risk (factors) is probably challenging for the physician and is prone for non-compliance. These challenges need to be addressed to achieve a decrease in CV morbidity and mortality in AS patients. It is therefore important that CV-RM in AS patients should be a joint effort for the primary care physician and treating rheumatologist. We should strive for increased awareness of CV risk and need to identify and target high-risk individuals for primary and secondary prevention.
A major strength of this study is the in-depth evaluation of CV risk and CV risk factors. We estimated CV risk according to various CV-RM assessment tools, thereby giving an overview of the different outcomes on CV risk in this AS population. However, only AS patients with active disease and from a single rheumatology centre were included which hampers generalizability. Finally, due to the retrospective design of this study, there was no data available on the reasons why CV risk treatment was suboptimal. This complicates further evaluation of CV-RM implementation, as it is possible that increased CV risk is acknowledged but treatment is not initiated because of side effects, comorbidity, or patients' non-adherence.
Discussion
In this observational cohort study we observed increased rates of hypertension and smoking in patients with active AS when compared to the general Dutch background population. This observation together with a documented elevated CV risk in AS patients emphasizes the need for optimal CV-RM. The majority of patients at increased CV risk received treatment, but CV-RM remains an important challenge for treating physicians, as treatment targets were often not achieved.
Available studies of the prevalence of CV risk factors in AS patients yield varying results. These differences could be explained by the heterogeneity of study populations investigated. Given the close relationship between inflammation, CV risk factors, and CV risk, we choose to assess CV risk and its risk factors in AS patients with high disease activity. In this selected population, we observed higher prevalence rates of hypertension and smoking, but not hypercholesterolemia and overweight. Inflammation may deteriorate CV risk factors, but patients with active disease may also experience more pain and physical stiffness, which can induce physical inactivity, increasing the chance of overweight and hypertension. The common use of NSAIDs might also contribute to the increased prevalence of hypertension. In fact, although the blood pressure was not significantly different, anti-hypertensive agents were prescribed significantly more in AS patients on NSAIDs.
The number of patients at high CV risk varied widely depending on the CV risk algorithm that was used. According to the Dutch CV-RM guidelines, 7% of assessed AS patients was at high CV risk, while 22% and 29% were at high risk according to either the European or American CV-RM guidelines. Overall, 5% of AS patients was at high CV risk according to all three guidelines. The large variation between the different CV-RM guidelines is remarkable. Several factors can explain this variation. First, the clinical outcomes on which the different guidelines are based vary from 10-years CV risk to develop a fatal atherosclerotic CV event (European CV-RM guidelines), 10-years CV risk to develop a fatal or non-fatal myocardial infarction or stroke (2013 ACC/AHA guidelines), or to 10-years CV risk to develop a fatal or non-fatal atherosclerotic event (Dutch CV-RM guidelines). Second, all guidelines are applicable for different age categories, i.e. Dutch for 40–70, European for 40–65, and ACC/AHA for 40–79 years of age.
To date, it is recognized that systemic inflammation is an important CV risk factor. However, none of the CV-RM guidelines adjust for the inflammatory burden in AS patients, which could lead to underestimation of CV risk. The EULAR task force advised to use a multiplication factor of 1.5 to CV risk to adjust for the increased CV risk in RA when patients have a disease duration >10 years, rheumatoid factor or anti-cyclic citrullinated peptide positivity, or presence of extra-articular manifestations. The Dutch CV-RM guidelines add 15 years to the age of all RA patients to calculate CV risk, as is also applied in DM patients. Currently, due to lack of evidence, it is unknown if, and if yes, what modification factor for CV risk assessment in AS patients is most appropriate. To investigate the impact of a modification factor for the increased CV risk in AS patients, we used the same modification factors as used in RA, for our group of AS patients. When adding 15 years to the age of the AS patients in this cohort, the percentage of patients with high CV risk increases from 7% to 26%. Subsequently, undertreatment of this CV risk increased from 28% to 44%. Future studies should be conducted to investigate which CV risk stratification method most accurately predicts CV risk in AS patients.
Since most patients with AS die from complications of atherosclerosis, early identification and optimal CV-RM is of utmost importance. It is reassuring that the awareness of CV-RM was good, as the vast majority of AS patients at risk for CV disease received treatment. However, it is alarming to see that in 76% CV-RM was suboptimal, as treatment targets were not reached. Moreover, in none of AS patients needing secondary prevention of CV disease, treatment targets were reached. Undertreatment of CV risk (factors) can be caused by multiple factors. First, there might be a lack of awareness of the increased CV risk in AS patients in treating physicians. Second, CV-RM, including CV risk screening, treatment, and follow-up, is time consuming and lack of time to act on guidelines presents an additional hurdle. Also, it is not clear who has responsibility for CV-RM in AS patients, as this can be the primary care physician, the treating rheumatologist, or both. The number and complexity of available guidelines also impede their implementation. Finally, since AS is often diagnosed early in life, implementing a lifetime treatment with medication for CV risk (factors) is probably challenging for the physician and is prone for non-compliance. These challenges need to be addressed to achieve a decrease in CV morbidity and mortality in AS patients. It is therefore important that CV-RM in AS patients should be a joint effort for the primary care physician and treating rheumatologist. We should strive for increased awareness of CV risk and need to identify and target high-risk individuals for primary and secondary prevention.
A major strength of this study is the in-depth evaluation of CV risk and CV risk factors. We estimated CV risk according to various CV-RM assessment tools, thereby giving an overview of the different outcomes on CV risk in this AS population. However, only AS patients with active disease and from a single rheumatology centre were included which hampers generalizability. Finally, due to the retrospective design of this study, there was no data available on the reasons why CV risk treatment was suboptimal. This complicates further evaluation of CV-RM implementation, as it is possible that increased CV risk is acknowledged but treatment is not initiated because of side effects, comorbidity, or patients' non-adherence.
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