Practice Guidelines for the Management of LDL-Related Risk
Adding to the confusion for practitioners selecting appropriate recommendations for the management of LDL-related risk in individual patients is the multitude of published guidelines for special populations: children, the elderly, women, and patients with cardiometabolic risk or diabetes, CKD, and familial hypercholesterolemia, among others. The unique features of these guidelines are summarized in the Central Illustration. It is of interest to specifically review the newest recommendations for management of LDL-related risk in patients with CKD, which represent a change in the approach to lipoprotein targets of therapy.
Chronic Kidney Disease. The 2013 Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease, published by the Kidney Disease: Improving Global Outcomes (KDIGO) panel, represents a significant departure from the previous guidelines of the Kidney Disease Outcomes Quality Initiative group in 2003( and 2007. The international group of experts in nephrology, cardiology, epidemiology, and lipidology used the GRADE system for evaluation of the evidence. However, the group acknowledges that the recommendations are primarily supported by a few large RCTs and post hoc analyses of the subgroup of CKD patients from statin trials in the general population. In patients with CKD, an initial fasting lipid profile is recommended primarily for the purpose of identification of more severe forms of hypercholesterolemia or hypertriglyceridemia and to rule out remediable or secondary causes of dyslipidemia. However, evidence from the Alberta Kidney Disease Network has demonstrated that in patients with CKD who are not dependent on dialysis, the relationship between LDL-C and ASCVD events is weaker than in the general population. This may possibly be related to the atherogenic dyslipidemia often present in CKD, which is characterized by lower levels of LDL-C, elevated LDL particle concentration, an increase in small dense LDL, reduced HDL-C, and elevated triglycerides. Therefore, according to KDIGO guidelines, the measured LDL-C may be less useful as a marker of coronary risk among people with advanced CKD who are not dialysis dependent, and it does not serve as an indication for pharmacological treatment. Instead, therapy is guided by the absolute risk of coronary events based on patient age and stage of CKD or estimated glomerular filtration rate (eGFR) (Table 2). The rate of coronary death or incident MI among CKD patients age >50 years (both men and women) is consistently >10 per 1,000 patient-years, which is considered by these experts to indicate a potential benefit of statin therapy. Specific doses of individual statins are recommended for each stage of CKD or eGFR, and dose titration is not indicated according to the evidence reviewed. Statin therapy or combination therapy with statin and ezetimibe is not recommended in adults with dialysis-dependent CKD due to lack of evidence of ASCVD risk reduction in patients with stage V CKD. Epidemiologic evidence suggests that cardiovascular events in dialysis patients tend to be nonatherosclerotic and more likely related to heart failure and arrhythmias. However, therapy may be continued in patients already receiving therapy at the time of initiation of dialysis. The KDIGO guidelines suggest follow-up measurement of lipid levels only when the results would influence therapy: that is, monitoring of adherence to statin therapy or to assess 10-year cardiovascular disease (CVD) risk in younger CKD patients not currently on statin therapy. Further discussion of this approach will follow in the review of the newest guidelines from the ACC/American Heart Association (AHA) on the management of blood cholesterol.
Management of LDL-Related ASCVD Risk in Special Populations
Adding to the confusion for practitioners selecting appropriate recommendations for the management of LDL-related risk in individual patients is the multitude of published guidelines for special populations: children, the elderly, women, and patients with cardiometabolic risk or diabetes, CKD, and familial hypercholesterolemia, among others. The unique features of these guidelines are summarized in the Central Illustration. It is of interest to specifically review the newest recommendations for management of LDL-related risk in patients with CKD, which represent a change in the approach to lipoprotein targets of therapy.
Chronic Kidney Disease. The 2013 Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease, published by the Kidney Disease: Improving Global Outcomes (KDIGO) panel, represents a significant departure from the previous guidelines of the Kidney Disease Outcomes Quality Initiative group in 2003( and 2007. The international group of experts in nephrology, cardiology, epidemiology, and lipidology used the GRADE system for evaluation of the evidence. However, the group acknowledges that the recommendations are primarily supported by a few large RCTs and post hoc analyses of the subgroup of CKD patients from statin trials in the general population. In patients with CKD, an initial fasting lipid profile is recommended primarily for the purpose of identification of more severe forms of hypercholesterolemia or hypertriglyceridemia and to rule out remediable or secondary causes of dyslipidemia. However, evidence from the Alberta Kidney Disease Network has demonstrated that in patients with CKD who are not dependent on dialysis, the relationship between LDL-C and ASCVD events is weaker than in the general population. This may possibly be related to the atherogenic dyslipidemia often present in CKD, which is characterized by lower levels of LDL-C, elevated LDL particle concentration, an increase in small dense LDL, reduced HDL-C, and elevated triglycerides. Therefore, according to KDIGO guidelines, the measured LDL-C may be less useful as a marker of coronary risk among people with advanced CKD who are not dialysis dependent, and it does not serve as an indication for pharmacological treatment. Instead, therapy is guided by the absolute risk of coronary events based on patient age and stage of CKD or estimated glomerular filtration rate (eGFR) (Table 2). The rate of coronary death or incident MI among CKD patients age >50 years (both men and women) is consistently >10 per 1,000 patient-years, which is considered by these experts to indicate a potential benefit of statin therapy. Specific doses of individual statins are recommended for each stage of CKD or eGFR, and dose titration is not indicated according to the evidence reviewed. Statin therapy or combination therapy with statin and ezetimibe is not recommended in adults with dialysis-dependent CKD due to lack of evidence of ASCVD risk reduction in patients with stage V CKD. Epidemiologic evidence suggests that cardiovascular events in dialysis patients tend to be nonatherosclerotic and more likely related to heart failure and arrhythmias. However, therapy may be continued in patients already receiving therapy at the time of initiation of dialysis. The KDIGO guidelines suggest follow-up measurement of lipid levels only when the results would influence therapy: that is, monitoring of adherence to statin therapy or to assess 10-year cardiovascular disease (CVD) risk in younger CKD patients not currently on statin therapy. Further discussion of this approach will follow in the review of the newest guidelines from the ACC/American Heart Association (AHA) on the management of blood cholesterol.
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