Effect of Diabetes on Progression of Coronary Atherosclerosis
Effect of Diabetes on Progression of Coronary Atherosclerosis
Objectives: Our goal was to characterize coronary atherosclerosis progression and arterial remodeling in diabetic patients.
Background: The mechanisms that underlie adverse cardiovascular outcomes in diabetic patients have not been well characterized.
Methods: A systematic analysis was performed in 2,237 subjects in randomized controlled studies of atherosclerosis progression. The pattern of arterial remodeling, extent of coronary atherosclerosis, and disease progression was compared in subjects with and without diabetes.
Results: In association with more risk factors, diabetic patients demonstrated a greater percent atheroma volume (PAV) (40.2 ± 0.9% vs. 37.5 ± 0.8%, p < 0.0001) and total atheroma volume (TAV) (199.4 ± 7.9 mm vs. 189.4 ± 7.1 mm, p = 0.03) on multivariate analysis. A stronger correlation was observed between PAV and glycated hemoglobin (r = 0.22, p = 0.0003) than fasting glucose (r = 0.09, p < 0.0001), although the difference just failed to meet statistical significance after controlling for study. Diabetic patients exhibited a smaller lumen (291.1 ± 104.8 mm vs. 306.5 ± 108.2 mm, p = 0.005) but no difference in external elastic membrane (494.9 ± 166.9 mm vs. 498.8 ± 167.2 mm, p = 0.61) volumes. More rapid progression of PAV (0.6 ± 0.4% vs. 0.05 ± 0.3%, p = 0.0001) and TAV (–0.6 ± 2.5 mm vs. –2.7 ± 2.4 mm, p = 0.03) was observed in diabetic patients on multivariate analysis. Smaller external elastic membrane (482.5 ± 160.7 mm vs. 519.9 ± 166.9 mm, p = 0.03) and lumen (276.0 ± 100.3 mm vs. 310.1 ± 105.6 mm, p = 0.001) volumes were observed in diabetic patients treated with insulin despite the presence of a similar TAV (206.5 ± 88.6 mm vs. 209.9 ± 90.2 mm, p = 0.84). Intensive low-density lipoprotein cholesterol lowering in patients improved the rate of plaque progression, but only to the level observed in nondiabetic patients with suboptimal lipid control.
Conclusions: Diabetes is accompanied by more extensive atherosclerosis and inadequate compensatory remodeling. Accelerated plaque progression, despite use of medical therapies, supports the need to develop new antiatherosclerotic strategies in diabetic patients.
The global spread of diabetes mellitus is a major factor contributing to the prediction that cardiovascular disease will become the leading cause of mortality worldwide by 2020. Patients with diabetes have a markedly increased incidence of adverse cardiovascular events and less favorable outcomes from myocardial infarction or after coronary interventions. In addition to concomitant hypertension and dyslipidemia, increasing evidence suggests that impaired glycemic homeostasis has a direct influence on the formation and propagation of atherosclerotic plaque. This is likely to underscore the observation that even in the absence of ischemic symptoms the presence of diabetes confers a prospective risk of clinical events comparable to that observed in nondiabetic survivors of myocardial infarction. As a result, prevention and treatment of diabetes is a major component of strategies designed to reduce cardiovascular risk.
Elucidating the factors that promote cardiovascular disease in diabetes is critical for the development of new therapeutic approaches. The prevalence of hyperglycemia, hypertension, and dyslipidemia, in association with systemic inflammation and oxidative stress, accelerates the formation and propagation of atherosclerotic plaque. This underlies observations from small clinical and necropsy studies that diabetes is characterized by diffuse atherosclerosis, with a predilection for involvement of distal segments in relatively small vessels. However, no systematic assessment of the pattern of coronary atherosclerosis and associated arterial wall remodeling has been performed in a large cohort of diabetic patients by imaging of the entire thickness of the coronary artery wall.
Intravascular ultrasound (IVUS) permits evaluation of the influence of clinical characteristics on changes in coronary atheroma volume. More recently, IVUS has been employed to assess the impact of medical therapies on the natural history of plaque progression. The current study investigated the extent and progression of atherosclerosis and associated arterial wall remodeling in a large number of diabetic patients with coronary artery disease who underwent serial evaluation by IVUS.
Abstract and Introduction
Abstract
Objectives: Our goal was to characterize coronary atherosclerosis progression and arterial remodeling in diabetic patients.
Background: The mechanisms that underlie adverse cardiovascular outcomes in diabetic patients have not been well characterized.
Methods: A systematic analysis was performed in 2,237 subjects in randomized controlled studies of atherosclerosis progression. The pattern of arterial remodeling, extent of coronary atherosclerosis, and disease progression was compared in subjects with and without diabetes.
Results: In association with more risk factors, diabetic patients demonstrated a greater percent atheroma volume (PAV) (40.2 ± 0.9% vs. 37.5 ± 0.8%, p < 0.0001) and total atheroma volume (TAV) (199.4 ± 7.9 mm vs. 189.4 ± 7.1 mm, p = 0.03) on multivariate analysis. A stronger correlation was observed between PAV and glycated hemoglobin (r = 0.22, p = 0.0003) than fasting glucose (r = 0.09, p < 0.0001), although the difference just failed to meet statistical significance after controlling for study. Diabetic patients exhibited a smaller lumen (291.1 ± 104.8 mm vs. 306.5 ± 108.2 mm, p = 0.005) but no difference in external elastic membrane (494.9 ± 166.9 mm vs. 498.8 ± 167.2 mm, p = 0.61) volumes. More rapid progression of PAV (0.6 ± 0.4% vs. 0.05 ± 0.3%, p = 0.0001) and TAV (–0.6 ± 2.5 mm vs. –2.7 ± 2.4 mm, p = 0.03) was observed in diabetic patients on multivariate analysis. Smaller external elastic membrane (482.5 ± 160.7 mm vs. 519.9 ± 166.9 mm, p = 0.03) and lumen (276.0 ± 100.3 mm vs. 310.1 ± 105.6 mm, p = 0.001) volumes were observed in diabetic patients treated with insulin despite the presence of a similar TAV (206.5 ± 88.6 mm vs. 209.9 ± 90.2 mm, p = 0.84). Intensive low-density lipoprotein cholesterol lowering in patients improved the rate of plaque progression, but only to the level observed in nondiabetic patients with suboptimal lipid control.
Conclusions: Diabetes is accompanied by more extensive atherosclerosis and inadequate compensatory remodeling. Accelerated plaque progression, despite use of medical therapies, supports the need to develop new antiatherosclerotic strategies in diabetic patients.
Introduction
The global spread of diabetes mellitus is a major factor contributing to the prediction that cardiovascular disease will become the leading cause of mortality worldwide by 2020. Patients with diabetes have a markedly increased incidence of adverse cardiovascular events and less favorable outcomes from myocardial infarction or after coronary interventions. In addition to concomitant hypertension and dyslipidemia, increasing evidence suggests that impaired glycemic homeostasis has a direct influence on the formation and propagation of atherosclerotic plaque. This is likely to underscore the observation that even in the absence of ischemic symptoms the presence of diabetes confers a prospective risk of clinical events comparable to that observed in nondiabetic survivors of myocardial infarction. As a result, prevention and treatment of diabetes is a major component of strategies designed to reduce cardiovascular risk.
Elucidating the factors that promote cardiovascular disease in diabetes is critical for the development of new therapeutic approaches. The prevalence of hyperglycemia, hypertension, and dyslipidemia, in association with systemic inflammation and oxidative stress, accelerates the formation and propagation of atherosclerotic plaque. This underlies observations from small clinical and necropsy studies that diabetes is characterized by diffuse atherosclerosis, with a predilection for involvement of distal segments in relatively small vessels. However, no systematic assessment of the pattern of coronary atherosclerosis and associated arterial wall remodeling has been performed in a large cohort of diabetic patients by imaging of the entire thickness of the coronary artery wall.
Intravascular ultrasound (IVUS) permits evaluation of the influence of clinical characteristics on changes in coronary atheroma volume. More recently, IVUS has been employed to assess the impact of medical therapies on the natural history of plaque progression. The current study investigated the extent and progression of atherosclerosis and associated arterial wall remodeling in a large number of diabetic patients with coronary artery disease who underwent serial evaluation by IVUS.