Cardiovascular Aging and Acute Coronary Syndromes: Unique Challenges and Solutions for Our Elderly Patients

With our aging population and increased cardiovascular disease complexity, clinicians frequently encounter clinical dilemmas in the management of coronary artery disease in older adults. Clinical trials that have established the role of timely revascularization and specific pharmacotherapies in acute coronary syndromes predominantly included patients less than 75 years of age.¹ While aging increases the atherosclerotic burden, acute coronary syndromes are closely intertwined with geriatric syndromes like frailty, and sensory and cognitive decline. Further, co-morbid renal dysfunction resulting in elevated cardiac biomarkers at baseline, combined with non-specific symptoms at presentation, can make the diagnosis of acute coronary syndromes challenging and lead to delays in management. Through a review of the aging-related pathophysiological changes in the cardiovascular system, the impact of geriatric syndromes on cardiovascular outcomes, and age-appropriate management recommendations, this scientific statement by Damluji et al. addresses these existing knowledge gaps and offers practical pearls to aid the clinician in the management of coronary artery disease in the elderly.

How does cardiovascular aging increase the risk of acute coronary syndrome?

Physiological aging is associated with increased stiffness in the aorta that compromises coronary filling due to lower diastolic pressures. Increased impedance to ejection results in compensatory left ventricular hypertrophy which combined with the increased collagen deposition in the myocardium causes age-related diastolic dysfunction. Elevated left ventricular filling pressures further impact coronary perfusion negatively. These changes are not just limited to epicardial flow; coronary microcirculation is also affected by aging as a consequence of impaired endothelial function.² Lastly, age-related decline in the chronotropic response adds to the coronary supply and demand mismatch in the face of stressors.

Aging-related changes in the renal parenchyma mirror the changes in the myocardium and arterial vasculature. Owing to a higher prevalence of chronic kidney disease, increased predisposition to acute kidney injury due to tubular dysfunction, need for complex high-risk interventions for calcific atherosclerosis, and delays in diagnosis and management of acute coronary syndromes, renal aging increases cardiovascular morbidity and mortality in the elderly.

Understanding these pathophysiological mechanisms that predispose our elderly patients to a higher risk of myocardial ischemia and are further associated with a higher risk of morbidity would aid the clinician in providing patient-centric and individualized care to help improve outcomes.

How do geriatric syndromes impact cardiovascular outcomes and management strategies?

Aging is a heterogeneous process– two similar-aged patients with identical clinical presentation may undergo radically different treatments. This highlights the importance of incorporation of age-related physiological vulnerabilities or geriatric syndromes like multimorbidity, polypharmacy, frailty, , and sensory and cognitive decline in clinical decision-making. Multimorbidity (two or more chronic conditions) and polypharmacy (five or more chronic medications) are frequently noted in elderly patients with advanced coronary artery disease. These syndromes are often associated with increased risk for drug-drug interactions causing adverse events like falls, bleeding, and confusion, hence, appropriate drug deprescription and an individualized management approach are pertinent in the management of acute coronary syndromes in the elderly.³ Frailty is a physiological age-related decline in the physical reserves which affects an individual's capacity to cope with acute stressors. Objective clinical markers of frailty may include low hand grip strength, decreased gait speed, low physical activity, and unintentional weight loss.⁴ Because frail patients are at an increased risk of morbidity and further decline after acute clinical events, early focus on physical therapy and nutritional and cardiac rehabilitation are of paramount importance in their care. Just like frailty, aging-related sensory and cognitive decline that is often compounded by delirium makes it very challenging to assess a patient's overall goals of care, especially when urgent or emergent decision-making is warranted in the management of acute coronary syndromes. Hence, timely conversations and establishment of advanced directives, involvement of the family or healthcare proxy in shared-decision making, and a holistic approach towards care are essential tenets of acute coronary syndrome management in older adults.

How does the management of acute coronary syndrome differ in the geriatric population?

Immediate percutaneous revascularization has been shown to reduce cardiovascular morbidity and mortality in elderly patients presenting with ST-elevation myocardial infarction (STEMI) compared to fibrinolysis and is the standard of care regardless of age.^{5, 6} However, the role of early invasive management strategy with timely revascularization in elderly patients admitted with non-ST-elevation myocardial infarction (NSTEMI) is less well defined. While the rates of recurrent MI and urgent repeat revascularization are reduced with revascularization, there is no clear mortality benefit.^{7, 8} Compared to conservative management, patients are at higher risk for adverse bleeding outcomes with an invasive management approach, and this risk is further escalated in frail patients. Increased incidence of type 2 MI in elderly patients due to multiple co-morbidities and impaired endothelial function also contributes to this conundrum. Specific risk prediction tools to help prognosticate acute coronary syndromes in the geriatric population are lacking. Commonly used scores like the GRACE score can be heavily influenced by age, which in turn diminishes their discriminative function in the elderly. Finally, clinical factors like frailty, polypharmacy, multimorbidity, and cognitive impairment are not accounted for in any of these risk estimation scores.

With aging, significant changes are noted in the hepatic blood flow, renal function, and muscle mass, which can directly impact the dosing of guideline-directed medical therapy in the setting of an acute coronary syndrome. Weight-based dosing of medications, specifically intravenous antiplatelet medications like glycoprotein IIb/IIIa inhibitors (tirofiban, eptifibatide) and cangrelor, prasugrel, unfractionated heparin, low-molecular-weight heparin, and oral anti-thrombotic agents like apixaban (dose reduction is recommended if two of three factors are present: age80 years, body weight 60 kg and serum creatinine is 1.5 mg/dl) is warranted. From a pharmacodynamic standpoint, older adults have an increased sensitivity to preload reduction, and beta-blockers, hence, low doses should be trialed first with careful up-titration to avoid hemodynamic instability. While the principles for medical therapy for acute coronary syndrome management are similar in older adults compared to their younger counterparts, individualized decision-making with careful consideration of their overall ischemic and bleeding risk is critical. Elderly-ACS II randomized patients 75 years with an acute coronary syndrome undergoing early percutaneous revascularization to reduced – dose prasugrel or clopidogrel – the trial was terminated early due to futility as prasugrel failed to show superiority to clopidogrel in reducing ischemic outcomes and was associated with higher bleeding risk.⁹ Similar results were noted when ticagrelor was compared to clopidogrel in randomized and observational studies focused on elderly adults with acute coronary syndromes (POPular AGE).^{10, 11} Hence, clopidogrel is the preferred P2Y12 inhibitor in older adults, however, if a more potent agent is utilized to optimize ischemic outcomes, it should be de-escalated after the first month to clopidogrel, to minimize bleeding outcomes. Concomitant atrial fibrillation is commonly noted in older adults, and anticoagulation with dual anti-platelet therapy further exacerbates their bleeding risk. To minimize bleeding without compromising ischemic outcomes, the duration of triple therapy should be minimized with an early transition to dual therapy with clopidogrel and direct oral anticoagulant (DOAC). During outpatient follow-up, the de-escalation of therapies should be assessed regularly to reduce adverse outcomes.

Older adults are frequently diagnosed with complex coronary artery disease with multi-vessel involvement, left main disease, left ventricular dysfunction, and severe calcific disease with high SYNTAX scores. A Heart Team approach with geriatrics expertise to incorporate relevant age-related factors like frailty and cognitive impairment in decision-making is recommended in such situations. Finally, palliative care with a focus on preserving the patient's quality of life and symptom control is a viable alternative to surgical or percutaneous revascularization in patients with advanced geriatric syndromes, a poor functional baseline, or with prohibitive surgical risk. Establishing goals of care before the acute event can help avoid futile interventions in such situations. The role of multidisciplinary coordination with close involvement of cardiologists, geriatricians, family members, primary care physicians, nurses, pharmacists, nutritionists, and cardiac rehabilitation professionals in the care of the elderly cannot be over-emphasized, especially during transitions of care. In closing, older adults benefit tremendously from cardiac rehabilitation with a tailored approach towards self-efficacy and functional improvement, and patients should not be excluded from these beneficial therapies on account of frailty alone.^{12, 13}

Conclusion:

Management of acute coronary syndrome in older adults is extremely challenging owing to their anatomic complexity, physiological vulnerability, and age-related factors like frailty and cognitive impairment, with significant heterogeneity in their functional status and goals of care. These factors are not objectively assessed by contemporary risk-prediction tools, hence, an individualized, patient-centric, and holistic approach to acute coronary syndrome care with close involvement of the family members and geriatric expertise, is recommended to optimize the care of older adults with acute coronary syndromes.