Cardiac Risk Stratification is a very broad topic but simply can be defined as an assessment used to evaluate a patient's risk of developing cardiovascular disease (CVD) or the risk of a cardiac event occurring in noncardiac surgeries, also known as a perioperative risk assessment. This article will discuss both the risk assessment for CVD and the risk assessment in the perioperative setting.
Cardiovascular Disease AssessmentCardiovascular disease is categorized into four groups: coronary heart disease, cerebrovascular disease, peripheral artery disease, aortic atherosclerosis, and thoracic or abdominal aortic aneurysms. There are several established risk factors that can be further categorized into non-modifiable and modifiable risk factors. The importance of understanding the significance of risk assessment lies in the epidemiology of CVD. Cardiovascular disease is the number 1 cause of death globally and projected remain as the world’s major disease burden, accounting for > 23.6 million deaths per year by 2030 . It is a source of great morbidity and mortality as well as a large portion of economic loss, especially in low- to middle-income counties as reported by the World Health Organization ]. Reducing the incidence by primary prevention will play a great role however it is important to understand that medical therapy is only part of the overall solution. Adequate risk reduction through education will be paramount in risk reduction.
Cardiovascular Risk Factors
Risk factors for cardiovascular disease can be separated into non-modifiable and modifiable risk factors. These risk factors have been shown to have a cumulative effect over time, in that the progression of CVD is related to not only the number of risk factors present but also their persistence over a period of time. More simply, the risk of developing CVD increases with the number of risk factors acquired and length of time they have been present .
Non-modifiable risk factors are as follows: Age, Gender, and Family History. Specifically, these risk factors are permanent, and there is very little that can be done to decrease an established risk from these factors. Several studies have been shown that the prevalence of CVD increases with age where each decade of life above the age of 40 showed a significant increase in the prevalence of any vascular disease . The male gender has been shown to have a baseline increased risk than females across several different populations . Family history has been shown across multiple studies to be an independent risk factor for the development of CVD or future myocardial infarction, specifically parental family history . A positive family history for CVD is described as any 1st-degree relative who has undergone death or development of CVD before the age of 55 for males or 65 for females.
The remaining risk factors are modifiable and can be further categorized into include health conditions and lifestyle factors. Health conditions include hypertension, dyslipidemia, diabetes mellitus, and chronic kidney disease (CKD). Lifestyle factors include cigarette smoking, diet and exercise, obesity, and psychosocial factors.Hypertension has an abundant amount of evidence to support its role as a risk factor in developing CVD. A meta-analysis published in 2002 shows that blood pressure is “strongly and directly related to vascular (and overall) mortality”, showing that a difference of 20 mmHg of systolic or 10 mm Hg of diastolic pressure is associated with a nearly twofold difference in cardiovascular disease death rate . Dyslipidemia, defined as elevated total or LDL cholesterol, low HDL cholesterol, disturbances in lipoprotein metabolism, have all been shown be independently associated with CVD. Diabetes mellitus is considered a coronary heart disease (CHD) equivalent  secondary to finding that patients with diabetes only had a similar risk of myocardial infarction compared to those without diabetes but with a prior myocardial infarction . Chronic kidney disease is now also considered a CHD equivalent, just as diabetes mellitus is. Secondary to both proteinuria and a decreased glomerular filtration rate, it was shown that patients with even moderate renal impairment based on GFR and increased proteinuria were associated with an increase in all-cause and cardiovascular mortality compared to those with normal renal function . Cigarette smoking is associated with a higher risk of myocardial infarction and is related to the amount used, however, the benefits of cessation is significant regardless of the amount or length of use. One study showed that smokers who stopped smoking had a risk similar to that of a nonsmoker within two years of quitting in a population of patients who had suffered a prior myocardial infarction . Diet high in red meat and high-fat dairy products have been associated to have a higher risk of CHD . A risk reduction was shown with diets high in fiber and daily consumption of fruits and vegetables. Exercise has been shown to reduce CHD risk and overall cardiovascular mortality. Obesity was shown to have a direct relationship with CVD risk .
Cardiovascular Risk Assessment and ReductionCardiovascular risk can be assessed through several different risk models accounting for separate risk factors, some overlapping with other risk models. No single risk model is the supreme choice, although the ACC/AHA published guidelines in 2013 recommending the use of the ACC/AHA pooled cohort hard CVD risk score in the United States. Regardless of the risk model that is chosen, patients are categorized in a Low, Intermediate and High estimated 10-year risk for developing CVD. Based on the patient’s category, further therapy for primary prevention can be warranted, or lifestyle changes and reassessment is done. Primary medical prophylaxis usually involves aspirin or statin initiation, but can involve medical therapy to reduce other risk factors, e.g. smoking cessation, depression, hypertensive medication, etc.
Perioperative Risk Assessment
Perioperative risk assessment is used to evaluate a patient’s risk of perioperative cardiac morbidity and mortality in noncardiac surgeries. It helps to facilitate a patient's informed decision by providing a risk/benefit illustration of the surgical intervention. Any patient that is planned for a noncardiac surgery should be risk stratified as it forces clinicians to perform a thorough evaluation . Devereaux reports an estimated 1.4 - 3.9% of surgical procedures are complicated by major cardiac events . The assessment is patient and surgery-specific, taking into account independent predictors of risk. Several risk assessment tools are available. However, all take into account the patient's clinical history and physical regarding independent clinical markers, including their functional capacity and the type of surgery to be performed. Considering these important parameters leads the clinician and patient to make a decision: to either proceed with elective surgery or perhaps explore other therapies and defer surgical intervention.
Perioperative Risk Clinical Markers
The independent clinical markers that were used in large studies as risk predictors are coronary artery disease (CAD), prior heart failure, diabetes, and renal failure. Each of these predictors carries with it a relative risk of approximately 2.0 to 5.0  for major cardiac complications.
Diagnosed coronary artery disease (CAD) carries a relative risk of 2.9 for major cardiac complications in the perioperative setting . It is estimated that about 6.2% of the US adult population is affected by CAD , and occasionally, patients without any known history of CAD are diagnosed during preoperative evaluation only with an electrocardiogram (ECG) showing an old infarction. It is important to distinguish that known CAD is separate from active/recent acute coronary syndrome, with the latter carrying a higher risk of perioperative morbidity and mortality as well as postoperative incidence of major cardiac complications . Prior heart failure carries a relative risk of 2.1 for major cardiac complications in the perioperative setting  with acutely decompensated heart failure carrying even higher risk. Diabetes mellitus with perioperative insulin use, an established CAD equivalent, carries a relative risk of 3.5 for major cardiac complications . Chronic renal failure with perioperative serum creatinine greater than 2.0 mg/dL carries a relative risk of 5.2 for a major cardiac event .
Functional capacity is quantified and characterized by metabolic equivalents (METs), where "excellent" is greater than 10 METs, "good" is 7 to 10 METs, "moderate" is 4 to 6 METs, and poor is less than 4 METs . Patients with a poor functional capacity have a relative risk of 1.8 for major cardiac complications .
Different types of surgeries carry separate risks. By definition, a low-risk procedure is where the combined surgical and patient characteristics predict a risk of cardiac complication less than 1%; whereas, a high-risk procedure predicts a risk of greater than 1%. Generally, high-risk surgeries include any intraperitoneal, intrathoracic, or suprainguinal vascular procedure carrying a relative risk of 2.1 for major cardiac complication . Low-risk surgeries include endoscopic intervention, ophthalmologic procedures, minimally invasive procedures, superficial procedures, and electroconvulsive therapy. All other procedures fall under intermediate risk.
Additional conditions that should warrant evaluation and consideration is any severe symptomatic valvular disease, known pulmonary vascular disease, or any unexplained dyspnea. Both conditions cause a significant increase in the risk of perioperative major cardiac complication .
All these predictors of risk are used to calculate a patient’s percentage of major cardiac complications. There are several risk calculators, such as the Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program among others, that are useful to establish a baseline clinical risk to dictate further whether perioperative testing is necessary. Most commonly, RCRI is used to calculate the risk of a major cardiac complication. This tool was based on the works of Goldman et al. in 1977 and first published in 1999 by Lee et al. using the following six clinical markers risk is calculated:
Each parameter is given a point if met, and the patient is given a risk of major cardiac complication based on a relative RCRI score of 0 to 6. The rates of major cardiac complication with 0, 1, 2, or greater than or equal to 3 clinical markers were 0.4%, 0.9%, 6.6%, and 11% respectively.
Furthermore, the differences between emergency, urgent, and elective surgeries should be defined, as emergency surgery does not allow for and/or require a preoperative assessment, unlike urgent and elective surgeries. Emergency surgery is defined as a procedure in which life or limb is threatened if the patient is not taken to the operating room in less than 6 hours. In contrast to urgent surgery, where life or limb are threatened if not in the operating room within 6 to 24 hours. Elective surgery is any procedure that can be delayed safely for up to 1 year.
Perioperative Cardiac Testing
Who should be tested? Simply, the answer depends on whether the results change management. In 2014, the American College of Cardiology published a stepwise algorithm for assessment  regarding perioperative testing. Any patient who needs immediate surgery does not undergo preoperative cardiac testing. All other urgent and elective procedures require the following conditions to be treated and managed prior to proceeding to surgery: ACS, decompensated heart failure, significant arrhythmias, and severe valvular disease. If none are present, patients whose risk of major cardiac complication is greater than 1% with poor or unknown functional capacity should be considered for testing. Obtaining a preoperative electrocardiogram is reasonable in patients with known CAD or those who are undergoing a moderate to high-risk surgery . Cardiac stress testing was shown to only be beneficial for patients who are neither low or high risk by clinical assessment as the results can re-classify these moderate-risk patients into low and high categories based on results , which may help the clinician and patient reconsider intervention. The etiology of perioperative cardiovascular events has been reported to be secondary to catecholamine surges leading to coronary artery shear stress and increased oxygen demand, coronary artery atherosclerotic disease, hypoxic state, prothrombotic events, and a generalized inflammatory state . Of these causes, cardiac stress testing, especially in the perioperative setting, only tests for significant CAD but is not able to elaborate on the other etiologies.
Prophylactic percutaneous coronary intervention was once done to patients with stable CAD undergoing elective vascular surgery with the thought that these patients have a significant hospital and 30-day cardiac mortality rate . This was tested in the coronary artery revascularization prophylaxis (CARP) trial resulting in no mortality benefit by performing coronary artery revascularization before elective vascular surgery, extrapolating that stable CAD should be medically managed in the setting of elective noncardiac surgery .
Perioperative medical management has had several criticisms, especially surrounding the use of beta-blockers and statins in the perioperative setting. With the controversy surrounding DECREASE trials and subsequent results of the Perioperative Ischemic Evaluation (POISE) trial, it brought into question the role of beta-blockers in the perioperative setting.
Beta-blockers were initially shown to reduce mortality and incidence of cardiovascular complications for up to 2 years after surgery in a 1996 study . This was again shown in 1999 by Podermans with results that were astounding. This trial tested the use of bisoprolol in the setting of elective aortic surgery resulting in an absolute risk reduction from a standard risk of 35% to 3.5% risk in the beta-blocker group . The subsequent POISE trial was conducted to evaluate further and solidify the findings regarding the benefit of the beta-blockers. This trial had two findings: the primary endpoint showed a statistical benefit with the use in beta blockers, with a reduction in the risk of myocardial infarction, cardiac revascularization, and clinically significant atrial fibrillation 30 days after randomization compared to placebo . However, the secondary endpoint showed a significant excess in risk of death, stroke, and clinically significant hypotension and bradycardia . Conflicting endpoints, but both statistically significant. This study showed that beta-blockers given in high doses on the day of surgery have a risk. Thus, guideline therapy now states that patients who are already on beta-blockers should continue them, patients who are moderate to high risk of major cardiac complications are reasonable to start prior to the day of surgery. However, beta-blockers should not be started on the day of surgery. This is a class-III recommendation .
Statin therapy was also under criticism, however far much less than beta blockers. This was secondary to, again, DECREASE III and IV trials, reporting an exaggerated benefit of statin therapy and combined beta-blocker/statin therapy, respectively . Unfortunately, the results of most of the DECREASE trials were found to be fictitiously reported, and guidelines based on their findings were retracted . Regardless, other trials have shown benefit in lowering risk of major cardiac complications in the perioperative vascular surgery and with patients with known CAD in the perioperative setting, although not as high as the DECREASE III and IV trials . Guideline therapy suggests continuing statin on patients already on statins; initiation of statin is reasonable in patients undergoing vascular disease .
Alpha agonists (for example, clonidine) have no benefit in the perioperative setting to reduce major cardiac complications  and are not recommended for perioperative use . Use of angiotensin-converting enzyme inhibitors (ACEI) is reasonable to continue if the patient is already on ACEI, although there is not a significant difference in the reduction of major cardiac complications .
Anticoagulants must be determined considering the clinical history and the surgical procedure to be done. Surgical procedures with a low risk of bleeding may have anticoagulation continued. Patients with a high risk of thromboembolic disease (for example, patients with mechanical valves), it may be reasonable to continue anticoagulation if there is a low risk of bleeding. In general, therapeutic anticoagulants are discouraged because of their harmful effect on the ability to control and contain surgical blood loss ].
The role of antiplatelet agents is focused on patients who are already on long-term antiplatelet therapy, usually in the context of prior cardiac stent placement. However, one study showed that even in patients with an elevated operative risk, aspirin in the perioperative setting does not reduce the rate of all-cause mortality or non-fatal myocardial infarction and is associated with an increased risk of major bleeding . It is a class-III recommendation that the initiation or continuation of aspirin is not beneficial in patients undergoing elective noncardiac surgery who have not had previous coronary stenting unless the risk of ischemic events outweighs the risk of surgical bleeding. It is a class-I recommendation that patients undergoing urgent surgery during the first 4 to 6 weeks after cardiac stent placement, dual antiplatelet therapy (DAPT) should be continued unless the relative risk of bleeding outweighs the benefit of the prevention of stent thrombosis. In patients with cardiac stents, if the surgical procedure requires discontinuation of DAPT, these patients should be continued on aspirin, and complete DAPT should be restarted as soon as possible .
Cardiac risk stratification is a very useful assessment and very patient-specific regarding the decision to proceed to surgery. It is an assessment requiring the entire healthcare team to participate to provide the best care to our patients. Evidence-based guideline therapy is not all-inclusive, however, has brought us closer to providing prediction and expectation in the perioperative setting. As continued research is performed, advancements in testing, improved patient care, and cost-effectiveness will bring us closer to risk reduction and making the best decision in the perioperative setting.