How can reducing elevated Low-Density Lipoprotein (LDL) cholesterol, Hemoglobin A1C (A1C), and Hypertension decrease the risk of major Cardiovascular (CV) events?

Reducing Elevated LDL, A1C, and Hypertension to Decrease Risk of Major CV Events

Reducing elevated LDL cholesterol, A1C, and blood pressure significantly decreases the risk of major cardiovascular events and death, with each 38.7 mg/dL reduction in LDL-C resulting in approximately 22% reduction in cardiovascular disease risk. 1

Benefits of Reducing LDL Cholesterol

• Each 1-mmol/L (38.7-mg/dL) reduction in LDL-C results in approximately 22% reduction in cardiovascular disease risk across all baseline LDL-C levels 1
• Lowering LDL-C reduces the relative risk for major coronary events by approximately 24% per 38.7-mg/dL reduction 1
• Total mortality is reduced by approximately 10% per 38.7-mg/dL LDL-C reduction, primarily due to a 16% reduction in the risk for cardiac death 1
• The risk for cardiovascular mortality is reduced by approximately 14% per 38-mg/dL LDL-C reduction 1
• The risk for nonfatal myocardial infarction is reduced by approximately 27% per 38.7-mg/dL LDL-C reduction 1
• The risk for first stroke is reduced by approximately 16% per 38.7-mg/dL LDL-C reduction, primarily due to a 21% reduction in the risk for ischemic stroke 1
• Larger absolute reductions in LDL-C are associated with greater reductions in cardiovascular disease risk 1

Benefits of Blood Pressure Control

• Aggressive blood pressure control in patients with diabetes reduces cardiovascular disease events by a relative 50% 1
• Treatment of isolated systolic hypertension in older patients with diabetes reduces cardiovascular disease events by a relative 34-69% 1
• Treatment with ACE inhibitors or ARBs in patients with diabetes and at least one other cardiovascular risk factor reduces cardiovascular events by a relative 22% and all-cause mortality by a relative 16% 1
• Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction 2
• The absolute risk increase per mmHg is greater at higher blood pressures, so even modest reductions of severe hypertension can provide substantial benefit 2

Benefits of Glycemic Control

• Tight glycemic control in patients with type 2 diabetes shows a trend toward reduced cardiovascular events, with lower rates of myocardial infarction (14.7 vs. 17.4 events per 1000 patient-years) and sudden death (0.9 vs. 1.6 events per 1000 patient-years) compared to conventional management 1
• Maintaining hemoglobin A1C below 7.0% is a reasonable goal for many non-pregnant adults with diabetes to reduce microvascular and macrovascular complications 3

Synergistic Effects of Combined Risk Factor Control

• In patients with type 2 diabetes, reducing both LDL-C and systolic blood pressure to lower targets (LDL-C ≤70 mg/dL and SBP ≤115 mmHg) results in regression of carotid intima-media thickness and greater decrease in left ventricular mass compared to standard targets (LDL-C ≤100 mg/dL and SBP ≤130 mmHg) 4
• Combining multiple risk factor interventions provides additive benefits for cardiovascular risk reduction 4

Practical Recommendations for Patients

For LDL Cholesterol Reduction:

• Explain that statins are the cornerstone of therapy for reducing LDL cholesterol and cardiovascular risk 1
• Emphasize that statins reduce the risk of major coronary events by approximately 24% for each 38.7 mg/dL reduction in LDL-C 1
• Highlight that statin therapy reduces total mortality by approximately 10% per 38.7 mg/dL LDL-C reduction 1
• Share that in the ASCOT-LLA trial, atorvastatin 10 mg reduced the risk of nonfatal myocardial infarction and fatal coronary heart disease by 36% compared to placebo 5
• In patients with diabetes, statin therapy reduced major cardiovascular events by 37% (HR 0.63) in the CARDS trial 5

For Blood Pressure Control:

• Explain that lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction 2
• Emphasize that aggressive blood pressure control in patients with diabetes can reduce cardiovascular disease events by up to 50% 1
• Highlight that ACE inhibitors or ARBs are particularly beneficial for patients with diabetes and hypertension 1, 2

For A1C Control:

• Explain that maintaining A1C below 7.0% helps reduce the risk of both microvascular and macrovascular complications 3
• Emphasize that tight glycemic control shows trends toward reduced rates of myocardial infarction and sudden death 1

Common Pitfalls and How to Avoid Them

• Clinical Inertia: Many patients do not achieve guideline-recommended LDL-C goals because therapy is not initiated or intensified appropriately. Implement systematic approaches to identify and treat patients not at goal 6
• Medication Adherence: Poor adherence to prescribed medications is a major barrier to achieving risk factor control. Discuss the importance of consistent medication use and address barriers to adherence 6
• Insurance Coverage: High-risk patients are frequently denied access to add-on therapies by insurance providers. Work with patients to navigate insurance challenges and consider alternative therapies when needed 6
• Underestimation of Risk: Patients often underestimate their cardiovascular risk. Use risk calculators and visual aids to help patients understand their personal risk 7
• Focusing on Single Risk Factors: Address all modifiable risk factors simultaneously for maximum benefit rather than focusing on just one 4, 7

Remember that there is no lower limit for LDL-C that has been identified as unsafe, and studies have found continuous benefit with no safety concerns in patients achieving LDL-C levels <25 mg/dL 6. Early, sustained reductions in LDL-C, blood pressure, and A1C are critical to slow or halt disease progression and reduce the risk of cardiovascular events and death.