Cardiovascular disease (CVD) is a dominant cause of sickness and death all over the world. It accounts for almost 30% of all-cause mortality in the world.1 Since the burden of CVD increases with age, it is not surprising that a major portion of the patients with CVD tend to be older and frailer with multiple comorbidities. Presence of a comorbid condition not only affects the disease progression in CVD but also profoundly influences clinical outcome and decision-making. It is a known that cardiovascular comorbidities such as hypertension, diabetes, atrial fibrillation, heart failure and stroke are independent predictors of risk and mortality in patients presenting to the emergency department of a hospital with acute myocardial infarction (AMI). However, the fact that many of the patients with CVD harbor a broad spectrum of noncardiovascular comorbidities receives less attention. The cardiovascular and noncardiovascular morbidities such as chronic obstructive pulmonary disease (COPD), liver cirrhosis, chronic kidney disease (CKD) and connective tissue disorders have a significant bearing on presentation, management and prognosis of CVD (Figs. 1 and 2).2
The Charlson comorbidity index (CCI) is a well-recognized measure of comorbid conditions.3 It quantifies prognostic impact of twenty-two comorbid conditions by means of a score—making it a useful tool for objective assessment of prognosis in multiple coexisting illnesses.
Different variables in Charlson comorbidity index with respective score are as follows:
- Cerebrovascular disease: 1
- Congestive heart failure: 1
- Peripheral vascular disease: 1
- Myocardial infarction: 1
- Connective tissue disease: 1
- Dementia: 1
- Peptic ulcer disease: 1
- Moderate-to-severe CKD: 2
- Leukemia: 2
- Hemiplegia: 2
- Malignant lymphoma: 2
- AIDS: 6
- Diabetes mellitus: 1 (if uncomplicated) and 2 (if end organ is damaged)
- Liver disease: 1 (if mild) and 2 (if moderate-to-severe)
- Solid tumor (any): 2
- Metastatic solid tumor: 6.
Many randomized controlled studies from a wide spectrum of populations have shown that majority of the patients with CVD have at least one comorbidity. Over the years, the prevalence of comorbidity has shown an upward trend. Conversely, the number of CVD patients without comorbidity has steadily fallen during the past couple of decades.
A meta-analysis by Rashid et al. looked at the impact of CCI on the outcomes in following cardiovascular conditions:
- Acute coronary syndrome (ACS)
- Stable coronary heart disease (CHD)
- Patients undergoing percutaneous intervention (PCI).
FIG. 1: Showing prognostic influence of cardiac and noncardiac comorbidities on cardiovascular events.Source: Canivell S, Muller O, Gencer B, et al. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome. PLoS One. 2018;13(4):e0195174.
FIG. 2: Showing impact of cardiac and noncardiac comorbidities on coronary events.Source: Canivell S, Muller O, Gencer B, et al. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome. PLoS One. 2018;13(4):e0195174.
ACUTE CORONARY SYNDROME WITH COMORBIDITIES
The risk of death in patients of ACS with a comorbidity increases proportionately with incremental increase in CCI score. Similarly, the risk of death was almost two times more in patients with any comorbidity (CCI >0) when compared to patients with no comorbidity (CCI = 0).
Jeger et al. reported in an ACS registry that the incidence of major adverse cardiovascular events (MACEs) increased with a CCI score—equal to or more than 2 during a 1-year follow-up period after ACS.4
In yet another study, Nunez et al. revealed that a higher CCI score is an independent predictor of mortality or AMI at 30 days and 1 year.5
RELATIONSHIP OF COMORBIDITY AND STABLE HEART DISEASE
It was revealed in the meta-analysis by Rashid et al. that an incremental increase in CCI score is associated with increased mortality even in stable heart disease.14
PATIENTS UNDERGOING PERCUTANEOUS INTERVENTION
Majority of the studies looking into the long-term survival after PCI for CAD have reported increased mortality with each point increase in CCI score.1
The conclusion of the study by Rashid et al. reveals that association of comorbidity has an inverse relationship to the survival outcomes in patients with heart disease. This finding has important implications in management of heart disease. Since the noncardiovascular comorbidities are usually not factored into while calculating mortality and survival outcomes in CHD unlike the traditional comorbid conditions such as diabetes, hyperlipidemia, hypertension, the findings of the study by Rashid et al. carry important long-term implications.
The mechanism by which the comorbid conditions such as CKD, liver cirrhosis, cerebrovascular disease influence outcomes in CVD is complex and multifactorial. Moreover, older and frailer patients with a relatively higher burden of comorbidity are likely to be treated with increased caution and often unwarranted conservative approach unlike the younger patients with no comorbid condition. For instance, it was found in a large, national ACS registry that there was an incremental reduction in the provision of evidence-based treatments such as aspirin, statins, angiotensin-converting enzyme (ACE) inhibitors and reperfusion therapy in older patients with multiple comorbid conditions.6 In another recent analysis involving 18,814 patients, Patel et al. reported that patients with comorbid burden, as defined by CCI score, were less likely to be offered coronary angiography and/or reperfusion therapy when presented with ST segment elevation myocardial infarction (STEMI).7 In addition, in the setting of acute ischemic stroke, thrombolysis is often denied to older patients with comorbidities due to fear of hemorrhage unlike the younger patients with no comorbidity.8 While managing chronic heart failure, deployment of ACE inhibitors and spironolactone is many a times withheld if there is a concurrent chronic kidney disease. Similarly, the treating physicians are often reluctant to use beta-blockers in elderly patients with chronic obstructive pulmonary disease.9
It is also true that aggressive treatment strategies in elderly patients with multiple comorbidities can result in adverse outcomes and heightened probability of complications. For instance, patients with leukemia are at an increased risk for in-stent thrombosis. Similarly, patients with liver cirrhosis have a greater likelihood of hemorrhage after PCI when antiplatelet agents are used. Consequently, the treating physicians face a daunting challenge to find a balance between the risks and benefits of a therapeutic intervention. The challenge is particularly stiff while managing patients with CHD and comorbidities in the present time because multiple treatment options such as medical therapies, PCI, surgical revascularization, device therapies and thrombolysis are now readily available to wider spectrum of patients.5
The author has faced many such challenges in his daily practice. Through this book, author intend to help his colleagues in cardiology to live up to the difficult task of managing patients of heart disease harboring various comorbid conditions. The author had to sift through a large amount of available literature on this subject before presenting this book so that the reader can make management decisions that are evidence-based. The author intend to drive home the message that there must be a thorough assessment of the comorbid status in patients of heart disease and that the impact of comorbidity on long-term survival must be integrated into the counseling of such patients. Any choice of treatment must be preceded by assessment of comorbid conditions apart from traditional risk assessment.
REFERENCES
- Rashid M, Kwok CS, Gale CP, et al. Impact of comorbid burden on mortality in patients with coronary heart disease, heart failure, and cerebrovascular accident: a systematic review and meta-analysis. Eur Heart J Qual Care Clin Outcomes. 2017;3:20–36.
- Canivell S, Muller O, Gencer B, et al. Prognosis of cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome. PLoS One. 2018;13(4):e0195174.
- Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40: 373–83.
- Jeger R, Jaguszewski M, Nallamothu BN, et al. Acute multivessel revascularization improves 1-year outcome in ST-elevation myocardial infarction: a nationwide study cohort from the AMIS Plus registry. Int J Cardiol. 2014;172:76–81.
- Nunez JE, Nunez E, Facila L, et al. Prognostic value of Charlson comorbidity index at 30 days and 1 year after acute myocardial infarction. Rev Esp Cardiol. 2004;57:842–9.
- Zaman MJ, Stirling S, Shepstone L, et al. The association between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myocardial Ischaemia National Audit Project (MINAP). Eur Heart J. 2014;35:1551–8.
- Patel N, Patel NJ, Thakkar B, et al. Management strategies and outcomes of ST-segment elevation myocardial infarction patients transferred after receiving fibrinolytic therapy in the United States. Clin Cardiol. 2016;39:9–18.
- Bateman BT, Schumacher HC, Boden-Albala B, et al. Factors associated with In-hospital mortality after administration of thrombolysis in acute ischemic stroke patients: an analysis of the nationwide inpatient sample 1999 to 2002. Stroke. 2006;37:440–6.
- Muzzarelli S, Maeder MT, Toggweiler S, et al. Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy. Am J Cardiol. 2012;109:693–8.