What is the risk of Major Adverse Cardiovascular Events (MACE) in males with Peripheral Artery Disease (PAD)?

Risk of Major Adverse Cardiovascular Events (MACE) in Males with Peripheral Artery Disease

Males with peripheral artery disease (PAD) face significantly elevated risks of major adverse cardiovascular events (MACE), with multiple risk amplifiers potentially compounding this risk beyond the baseline elevation associated with PAD alone.

PAD and Baseline MACE Risk

PAD represents a manifestation of systemic atherosclerosis that substantially increases cardiovascular risk regardless of gender. Key points about baseline risk:

• All patients with PAD have increased risk of MACE including stroke, myocardial infarction, heart failure, and cardiovascular death 1
• PAD is considered an atherosclerotic cardiovascular disease equivalent, placing patients in a high-risk category for cardiovascular events

Risk Amplifiers in Males with PAD

Several factors significantly increase MACE risk in PAD patients, with particular relevance to males:

Comorbid Conditions

• Diabetes: Increases risk of all-cause death (HR: 1.35 [95% CI: 1.15-1.60]) and MACE (HR: 1.47 [95% CI: 1.23-1.75]) 1
• Chronic Kidney Disease (CKD): Associated with higher rates of cardiovascular death, MI, and ischemic stroke (6.75 vs 3.72 events/100 patient-years; adjusted HR: 1.45) 1
• End-Stage Kidney Disease: Particularly high risk, with 5-year survival rates as low as 19% after renal transplantation in PAD patients 1

Behavioral Factors

• Ongoing smoking: 80-90% of patients requiring revascularization for severe limb symptoms are current smokers, with 5-year mortality rates of 40-50% in active smokers with symptomatic PAD 1

Disease Patterns

• Polyvascular disease: The presence of atherosclerotic disease in multiple vascular beds (coronary, peripheral, cerebrovascular) significantly compounds risk 1
  • Patients with both PAD and CAD have higher 5-year all-cause mortality (adjusted HR: 1.35) compared to those with CAD alone 1
  • Risk increases stepwise with each additional affected vascular bed (HR increasing from 1.47 to 2.33 to 3.12) 1

Psychological Factors

• Depression: Associated with increased MACE during longitudinal follow-up, with Geriatric Depression Score ≥6 linked to higher event rates 1

Specific MACE Risk in Males

While the 2024 ACC/AHA guidelines don't specifically stratify MACE risk by gender for PAD patients, several important considerations apply to males:

• Males with PAD typically have higher rates of smoking and polyvascular disease, which are significant risk amplifiers 1
• Males with PAD and concomitant CAD have particularly high risk of MACE, with studies showing MI occurring in 4.9% of PAD patients over just 30 months despite antiplatelet therapy 1

Risk Reduction Strategies

The following evidence-based interventions can reduce MACE risk in males with PAD:

Pharmacological Interventions

• Antihypertensive therapy: Should be administered with a target of <130/80 mmHg 1, 2

  • ACE inhibitors or ARBs are first-line agents, showing 25% reduction in risk of MI, stroke, and vascular death 1, 2
  • Beta-blockers are safe and do not adversely affect walking capacity 2

• Antithrombotic therapy:

  • For symptomatic PAD: Low-dose rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin reduces MACE and MALE 1
  • For asymptomatic PAD: Single antiplatelet therapy is reasonable to reduce MACE risk 1

• Lipid management:

  • High-intensity statin therapy to achieve LDL <70 mg/dL 2
  • For patients not achieving LDL <70 mg/dL on maximally tolerated statin therapy, adding PCSK9 inhibitors or ezetimibe is reasonable 1
  • PCSK9 inhibitors (evolocumab) showed lower MACE rates (HR: 0.79) in PAD patients 1

Lifestyle Modifications

• Smoking cessation: Critical intervention with highest priority 2
• Structured exercise program: At least 30-45 minutes, ≥3 times/week 2
• Weight reduction if overweight/obese 2

Monitoring and Follow-up

• Annual follow-up to assess clinical and functional status, medication adherence, and cardiovascular risk factors 2
• Regular blood pressure monitoring with measurements in both arms at least once during initial assessment 2
• Assessment for depression using tools like the Geriatric Depression Score (GDS) or Patient Health Questionnaire (PHQ)-9 1

Common Pitfalls in Managing Males with PAD

• Undertreatment: Less aggressive lipid management observed in PAD versus cardiovascular disease, highlighting missed opportunities for implementation of proven therapies 3
• Overlooking polyvascular disease: Males often have undiagnosed coronary or cerebrovascular disease that significantly increases MACE risk 1
• Focusing only on limb symptoms: While limb symptoms may be the presenting complaint, comprehensive cardiovascular risk reduction is essential 1
• Inadequate antithrombotic therapy: Despite evidence supporting intensive antithrombotic therapy, many patients receive suboptimal treatment 4

By identifying and addressing these risk amplifiers through comprehensive medical management, the elevated MACE risk in males with PAD can be significantly reduced.