A Structured Review of Microalbuminuria and Cardiovascular Event
A Structured Review of Microalbuminuria and Cardiovascular Event
Study Objective: To quantify the relative risk of cardiovascular events associated with microalbuminuria in patients with both diabetes mellitus and hypertension.
Design: A structured literature search from January 1990-December 2002 using MEDLINE, IPA, and CINAHL.
Measurements and Main Results: We identified original studies that reported the presence or absence of microalbuminuria and estimates of risk associated with cardiovascular events in patients with both diabetes and hypertension. Abstracted information consisted of study design, patient demographics and risk factors, treatment regimens, and outcome variables. Point estimates and confidence intervals for relative risk were calculated from available data. Of 651 citations identified and reviewed based on title and abstract, 72 were selected for full review. Seven met the inclusion criteria. Because of lack of homogeneity among studies, the results were not conducive to pooling. Cardiovascular end points associated with the presence of microalbuminuria in these studies were all-cause mortality, cardiovascular mortality, and composite cardiovascular morbidity. The relative risk of cardiovascular end points associated with the presence of microalbuminuria ranged from 1.6 (95% confidence interval [CI] 1.2-2.2) to 7.9 (95% CI 2.5-25.3).
Conclusion: From the limited information available, the risk of cardiovascular events and mortality is estimated to be 2-8 times higher when microalbuminuria is present in patients with diabetes and hypertension. Point estimates in relative risk of cardiovascular morbidity and mortality in patients with diabetes and hypertension were generally higher compared with studies estimating risk in those with only diabetes. Studies that examine the relationship between microalbuminuria (scaled as a continuous or ordinal variable) and cardiovascular events are necessary to clarify potential benefits of pharmacotherapies that reduce levels of urinary albumin.
Cardiovascular disease is a leading cause of morbidity and mortality in the Unites States. Although it has many risk factors, diabetes mellitus and hypertension are among the most significant. Individuals with diabetes have a 2-4-fold increased risk of subsequent cardiovascular disease over those who do not have diabetes. Those with both diseases would be suspected to be at even greater risk. Several primary and secondary interventions reduce the risk of cardiovascular morbidity and mortality in a high-risk diabetic population, including ensuring optimum serum lipid profiles, glycemic and blood pressure control, smoking cessation, postmyocardial infarction β-blockade, angiotensin-converting enzyme (ACE) inhibitor therapy for left ventricular dysfunction, weight reduction, and diet modification. Despite these best practices, however, mortality associated with cardiovascular disease in patients with diabetes continues to be higher than that in those without the disease.
Increased attention has been given to the role of microalbuminuria as a cardiovascular risk indicator, particularly in patients with diabetes and hypertension. Microalbuminuria typically is defined as a urinary albumin excretion (UAE) rate (or albumin excretion rate [AER]) of 30-299 mg/day or an albumin:creatinine ratio (ACR) of 2.5-25 mg/mmol in men and 3.5-25 mg/mmol in women. In cross-sectional studies, the prevalence of microalbuminuria was 20-40% in patients with diabetes and 10-15% in middle-aged individuals without diabetes. Microalbuminuria is an independent predictor of stroke, death, and myocardial infarction. Moreover, in persons with diabetes and microalbuminuria, the risk of cardiovascular morbidity and mortality is estimated to be 1.8 times greater than for those with normoalbuminuria. Although pharmacotherapies that reduce or prevent progression of microalbuminuria lower risk of progression to overt nephropathy, their effects in lowering subsequent cardiovascular morbidity and mortality have yet to be documented.
Many clinical factors complicate the understanding of the association between microalbuminuria and risk of cardiovascular morbidity and mortality. A key issue in understanding the relationship is to recognize that more than one risk factor (hyperglycemia, hypertension) may modify and contribute to a cardiovascular event. Studies that examine the association are important for obtaining insight into the future role of pharmacotherapies that directly or indirectly alter albumin levels. However, the extent to which a progressive graded relationship exists is unclear. Furthermore, the definition of microalbuminuria is based on its ability to predict diabetic nephropathy (macroalbuminuria, clinical proteinuria) rather than on cardiovascular morbidity and mortality.
We reviewed the literature on microalbuminuria and its relationship to cardiovascular events in high-risk patients diagnosed with both diabetes and hypertension. The specific objectives were to determine the risk associated with elevated microalbuminuria and cardiovascular events (myocardial infarction, heart failure, stroke, death) in studies of patients with diabetes and hypertension, and to identify and summarize the findings of studies that investigated the association between incremental changes in the levels of microalbuminuria and risk of cardiovascular events as a consequence of anti-hypertensive pharmacotherapy.
Study Objective: To quantify the relative risk of cardiovascular events associated with microalbuminuria in patients with both diabetes mellitus and hypertension.
Design: A structured literature search from January 1990-December 2002 using MEDLINE, IPA, and CINAHL.
Measurements and Main Results: We identified original studies that reported the presence or absence of microalbuminuria and estimates of risk associated with cardiovascular events in patients with both diabetes and hypertension. Abstracted information consisted of study design, patient demographics and risk factors, treatment regimens, and outcome variables. Point estimates and confidence intervals for relative risk were calculated from available data. Of 651 citations identified and reviewed based on title and abstract, 72 were selected for full review. Seven met the inclusion criteria. Because of lack of homogeneity among studies, the results were not conducive to pooling. Cardiovascular end points associated with the presence of microalbuminuria in these studies were all-cause mortality, cardiovascular mortality, and composite cardiovascular morbidity. The relative risk of cardiovascular end points associated with the presence of microalbuminuria ranged from 1.6 (95% confidence interval [CI] 1.2-2.2) to 7.9 (95% CI 2.5-25.3).
Conclusion: From the limited information available, the risk of cardiovascular events and mortality is estimated to be 2-8 times higher when microalbuminuria is present in patients with diabetes and hypertension. Point estimates in relative risk of cardiovascular morbidity and mortality in patients with diabetes and hypertension were generally higher compared with studies estimating risk in those with only diabetes. Studies that examine the relationship between microalbuminuria (scaled as a continuous or ordinal variable) and cardiovascular events are necessary to clarify potential benefits of pharmacotherapies that reduce levels of urinary albumin.
Cardiovascular disease is a leading cause of morbidity and mortality in the Unites States. Although it has many risk factors, diabetes mellitus and hypertension are among the most significant. Individuals with diabetes have a 2-4-fold increased risk of subsequent cardiovascular disease over those who do not have diabetes. Those with both diseases would be suspected to be at even greater risk. Several primary and secondary interventions reduce the risk of cardiovascular morbidity and mortality in a high-risk diabetic population, including ensuring optimum serum lipid profiles, glycemic and blood pressure control, smoking cessation, postmyocardial infarction β-blockade, angiotensin-converting enzyme (ACE) inhibitor therapy for left ventricular dysfunction, weight reduction, and diet modification. Despite these best practices, however, mortality associated with cardiovascular disease in patients with diabetes continues to be higher than that in those without the disease.
Increased attention has been given to the role of microalbuminuria as a cardiovascular risk indicator, particularly in patients with diabetes and hypertension. Microalbuminuria typically is defined as a urinary albumin excretion (UAE) rate (or albumin excretion rate [AER]) of 30-299 mg/day or an albumin:creatinine ratio (ACR) of 2.5-25 mg/mmol in men and 3.5-25 mg/mmol in women. In cross-sectional studies, the prevalence of microalbuminuria was 20-40% in patients with diabetes and 10-15% in middle-aged individuals without diabetes. Microalbuminuria is an independent predictor of stroke, death, and myocardial infarction. Moreover, in persons with diabetes and microalbuminuria, the risk of cardiovascular morbidity and mortality is estimated to be 1.8 times greater than for those with normoalbuminuria. Although pharmacotherapies that reduce or prevent progression of microalbuminuria lower risk of progression to overt nephropathy, their effects in lowering subsequent cardiovascular morbidity and mortality have yet to be documented.
Many clinical factors complicate the understanding of the association between microalbuminuria and risk of cardiovascular morbidity and mortality. A key issue in understanding the relationship is to recognize that more than one risk factor (hyperglycemia, hypertension) may modify and contribute to a cardiovascular event. Studies that examine the association are important for obtaining insight into the future role of pharmacotherapies that directly or indirectly alter albumin levels. However, the extent to which a progressive graded relationship exists is unclear. Furthermore, the definition of microalbuminuria is based on its ability to predict diabetic nephropathy (macroalbuminuria, clinical proteinuria) rather than on cardiovascular morbidity and mortality.
We reviewed the literature on microalbuminuria and its relationship to cardiovascular events in high-risk patients diagnosed with both diabetes and hypertension. The specific objectives were to determine the risk associated with elevated microalbuminuria and cardiovascular events (myocardial infarction, heart failure, stroke, death) in studies of patients with diabetes and hypertension, and to identify and summarize the findings of studies that investigated the association between incremental changes in the levels of microalbuminuria and risk of cardiovascular events as a consequence of anti-hypertensive pharmacotherapy.
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