Atherosclerotic cardiovascular disease (ASCVD) is the most common macrovascular complication in patients with diabetes. Over 40% of diabetes-related deaths are attributed to cardiovascular diseases, particularly ASCVD. Among hospitalized patients with coronary heart disease (CHD), more than 40% have either pre-existing or newly diagnosed diabetes. Blood glucose levels are positively correlated with the risk of developing CHD.
Pathogenesis
The mechanisms by which diabetes contributes to the development of CHD are complex and are thought to involve factors such as endothelial dysfunction, increased inflammation, lipid metabolism abnormalities, oxidative stress, and hypercoagulable states, all of which are driven by hyperglycemia and insulin resistance.
Endothelial Dysfunction
Hyperglycemia directly suppresses endothelium-dependent vasodilation. Hyperinsulinemia exacerbates endothelial dysfunction by promoting the production of endothelin-1, angiotensin II, and reactive oxygen species (ROS), leading to atherosclerosis and thrombosis.
Increased Inflammation
The accumulation of advanced glycation end products (AGEs) and other metabolic byproducts increases the infiltration of inflammatory cells and the expression of inflammatory and tissue factors at lesion sites. This systemic increase in inflammation accelerates the formation of atherosclerotic plaques.
Lipid Metabolism Abnormalities
Approximately 60-70% of patients with diabetes have dyslipidemia, typically characterized by elevated triglycerides, low levels of HDL-C, and high levels of apo B-containing lipoproteins. LDL-C in diabetic patients is more atherogenic, and even those with normal LDL-C levels are at higher risk of developing atherosclerosis. Elevated free fatty acid levels impair insulin signaling, promote inflammation, and exacerbate thrombosis, accelerating the progression of atherosclerosis.
Oxidative Stress
AGEs activate their receptors (RAGE), stimulating NADPH oxidase 1 and increasing ROS production. Mitochondrial dysfunction in diabetes further elevates ROS levels. Excessive ROS contributes to processes such as cell proliferation, migration, endoplasmic reticulum stress, autophagy, senescence, and apoptosis, playing a critical role in the initiation and progression of atherosclerosis.
Hypercoagulable State
Both hyperinsulinemia and hyperglycemia increase the procoagulant activity of circulating tissue factors and the expression of prothrombotic proteins (e.g., PAI-1 antigen, vWF antigen, fibrinogen, and coagulation factors II, V, VII, VIII, and X). This leads to a higher incidence of atherosclerotic plaque embolization in diabetic patients. Additionally, elevated levels of soluble P-selectin and CD40 ligand in diabetes result in excessive platelet activation, promoting thrombosis and accelerating vascular narrowing and occlusion.
Clinical Manifestations
Patients with diabetes and CHD often exhibit the following clinical characteristics:
Silent Myocardial Ischemia
This refers to objective evidence of myocardial ischemia without symptoms such as chest discomfort or pain. Its prevalence is significantly higher in diabetic patients than in those without diabetes, increasing the risk of missed CHD diagnoses. This may be related to elevated pain perception thresholds and autonomic neuropathy in diabetes.
Diffuse Vascular Lesions and Calcification
Diabetic patients with CHD often present with diffuse atherosclerotic lesions, significant vascular calcification, reduced collateral circulation, and a higher incidence of left main coronary artery disease.
Microvascular Disease
Some diabetic patients may experience chest discomfort or pain and objective evidence of myocardial ischemia, while coronary angiography only reveals mild atherosclerotic changes that do not match the severity of clinical symptoms. This discrepancy is often attributed to microvascular disease, which can be diagnosed using myocardial perfusion imaging.
Diagnosis and Differential Diagnosis
These can be seen in the relevant sections on Coronary Heart Disease and Diabetes.
Treatment
Lifestyle Interventions
Lifestyle modifications form the foundation of treatment and should be maintained throughout the course of therapy. These include:
- A low-salt, low-fat, and diabetes-friendly diet.
- Regular physical activity (typically 150 minutes of moderate-intensity exercise or 75 minutes of high-intensity exercise per week).
- Avoidance of harmful habits such as smoking and alcohol consumption.
- Maintaining a positive mental state.
For overweight and obese individuals, reducing caloric intake and engaging in regular exercise to achieve weight loss can help lower the risk of cardiovascular events.
Glucose-Lowering Therapy
Glucose Control Targets
Blood glucose targets should follow an individualized approach. For most patients, HbA1c should be maintained at <7.0%. For patients with long disease durations, limited life expectancy, advanced age, or frailty, less stringent glucose control targets may be appropriate.
Choice of Glucose-Lowering Medications
GLP-1 receptor agonists and/or SGLT2 inhibitors with proven cardiovascular benefits are recommended as first-line therapies. For patients with coexisting heart failure or chronic kidney disease, SGLT2 inhibitors are preferred. If blood glucose control remains inadequate, additional medications such as metformin, DPP-4 inhibitors, or other agents with cardiovascular safety profiles may be added.
Treatment of Coronary Heart Disease
This can be seen in the relevant sections on Coronary Heart Disease.