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Risk Factors For Coronary Artery Disease


Risk Factors For Coronary Artery Disease

Article Author:
Jonathan Brown
Article Author:
Thomas Gerhardt
Article Editor:
Edward Kwon
Updated:
6/6/2020 2:59:06 PM
For CME on this topic:
Risk Factors For Coronary Artery Disease CME
PubMed Link:
Risk Factors For Coronary Artery Disease

Introduction

Coronary artery disease (CAD) accounts for approximately 610,000 deaths annually (estimated 1 in 4 deaths) and is the leading cause of mortality in the United States.[1] It is the third leading cause of mortality worldwide and is associated with 17.8 million deaths annually.[2][3][4][5] Healthcare services for CAD are estimated to cost greater than 200 billion dollars annually in the United States.[6] While CAD is a significant cause of death and disability, it is preventable. 

The Framingham Heart Study enrolled its first participant in 1948 and is currently studying its third generation of participants.[7][8] This was the first study that elucidated risk factors associated with cardiovascular disease. Since then, cohort studies have continued to study the impact of different risk factors on cardiovascular disease. The FINRISK study is an ongoing Finnish population-based observational study that began in 1972.[9]  The  ULSAM, PIVUS, POEM, EpiHealth, and SCAPIS studies were cohort studies completed at Uppsala University in Sweden.  The PREDICT Cardiovascular Disease Cohort study was another study completed in New Zealand.[10]  These studies classify CAD into two broad categories: non-modifiable and modifiable risk factors.  Non-modifiable risk factors include age, gender, ethnicity, and family history of CAD.  Modifiable risk factors include hypertension, hyperlipidemia, diabetes, obesity, smoking, poor diet, sedentary lifestyle, and stress.[7][11]

Given the immense healthcare burden of CAD, modifiable, and non-modifiable risk factors were identified to mitigate the resulting economic and disease-related burden. Risk factor identification, combined with advances in medical technology, has contributed to a significant decrease in CAD mortality rates over the past forty years in western countries.  One public health study that gathered mortality data from 1969 to 2014 concluded that by 2020, the number of heart disease-related deaths would decrease by 21.3 percent for men and 13.4 percent in women.[12]

This article will review the impact and management of these risk factors. Ever since the Framingham Heart Study, there has been a plethora of data on coronary artery disease risk factors.  This piece will provide a concise summary of the most recent systemic reviews and evidence.  

Issues of Concern

Risk factors for coronary artery disease classify into modifiable and non-modifiable risk factors.  

A 2019 article indicated that age, sex, and race captured 63 to80% of prognostic performance, while modifiable risk factors contributed only modestly. Yet, control of modifiable risk factors led to substantial reductions in CAD events.[11] Non-modifiable risk factors are discussed first:  

  • Age: CAD prevalence increases after 35 years of age in both men and women.  The lifetime risk of developing CAD in men and women after 40 years of age is 49% and 32%, respectively.[13]
  • Gender: Men are at increased risk compared to women.
  • Ethnicity: African Americans, Hispanics, Latinos, and Southeast Asians, are ethnic groups with an increased risk of CAD morbidity and mortality.[14][15][16]
  • Family history: Family history is also a significant risk factor.  Patients with a family history of premature cardiac disease younger than 50 years of age have an increased CAD mortality risk.[17] A separate article indicated that a father or brother diagnosed with CAD before 55 years of age, and a mother or sister diagnosed before 65 years of age are considered risk factors.[7]

Modifiable risk factors have a smaller but still significant role.[11] Yet, only two-thirds of patients receive optimal medication interventions.[18] If this were achieved, there would be a substantial reduction in CAD events.[11] One study observed that those with optimal risk factor profiles had a substantially lower rate of death from cardiovascular events.[19]

  • Hypertension: 
    • About 1 out of every three patients have hypertension. Hypertension and smoking were responsible for the largest number of deaths in a 2009 review comparing twelve modifiable risk factors.[20] Yet, only 54% of these patients achieve adequate blood pressure control.[21]
    • Hypertension has long been a major risk factor for heart disease through both oxidative and mechanical stress; it places on the arterial wall.[22][23]
    • A 1996 article reported that in the Framingham cohort, a systolic of 20mmHg and diastolic of 10 mmHg increase was observed from age 30 years to 65 years.[24]
  • Hyperlipidemia:
    • Hyperlipidemia is considered the second most common risk factor for ischemic heart disease.[18]
    • According to the World Health Organization, raised cholesterol caused an estimated 2.6 million deaths.[18]   
    • A recent cross-sectional study utilizing the coronary calcium score indicated a 55%, 41%, and 20% higher prevalence of hypercholesterolemia, combined hyperlipidemia, and low HDL-c, respectively.[25]
    • Elevated triglycerides have also been implicated in coronary artery disease; however, the relationship is more complicated as the association becomes attenuated when adjusted for other risk factors such as central adiposity, insulin resistance, and poor diet. Thus, it is challenging to determine an isolated effect of triglycerides on coronary artery disease.[26]
  • Diabetes mellitus:  
    • The Center for Disease Control (CDC) reports that more than one out of every three adult patients in the United States have prediabetes, which puts one at risk of developing type 2 diabetes, heart disease, and stroke. 
    • The heart disease rate is 2.5 times higher in men and 2.4 times higher in women in diabetic adult patients compared to those without diabetes.[18]
    • A 2017 meta-analysis indicated that diabetic patients with an A1C > 7.0 had an 85% higher likelihood (hazard ratio 1.85, 95% CI 1.14-2.55) of cardiovascular mortality, compared to those with an A1C < 7.0%.  It also revealed that non-diabetic patients with an A1C > 6.0% had a 50% higher likelihood (hazard ratio, 1.50, 95% CI 1.01-2.21) of cardiovascular mortality compared to those with an A1C of < 5.0%. Researchers also reported a significant study heterogeneity.[27]  
    • Cardiovascular disease is the leading cause of morbidity and mortality in patients with diabetes.[28]
  • Obesity:   
    • 69% of adults in the United States are overweight or obese.  35% of adults are obese.[18]
    • Obesity is an independent risk factor for CAD and also increases the risk of developing other CAD risk factors, including hypertension, hyperlipidemia, and diabetes mellitus.[29][30][31] 
    • One recent study indicated that obese patients were twice as likely to have coronary heart disease (hazard ratio 2.00, 95% CI 1.67-2.40) after adjustment for demographics, smoking, physical activity, and alcohol intake.[32]
    • A 1998 research study and 2016 review article conferred that obesity is associated with more complex, raised, and hi-grade atherosclerotic coronary artery lesions.[33][34]
    • The "obesity paradox" has also been reported. Despite evidence pointing to obesity as an independent risk factor for cardiovascular morbidity, some authors have described better outcomes in overweight and obese patients.  There is an ongoing debate in light of this conflicting data.[35]
  • Smoking:
    • The Food & Drug Administration (FDA) estimates that cardiovascular disease causes 800,000 deaths and 400,000 premature deaths per year. About one-fifth and one-third of these result from smoking, respectively. 
    • A 2015 meta-analysis revealed that smoking resulted in a 51% increased risk (21 studies, RR 1.51, 95% CI 1.41.1-62) of coronary heart disease in diabetic patients.[36]
    • A separate 2015 meta-analysis revealed that smoking resulted in twice the risk of cardiovascular disease for current smokers and a 37% increase in risk with former smokers, among patients > 60 years old.[37] 
    • Nonsmokers regularly exposed to second-hand smoke also have a 25 to 30% increased risk of coronary heart disease compared to those not exposed.[38]
  • Poor diet: 
    • The association between saturated fat and coronary heart disease has been a journey. Initially, thought to be a significant causative factor in the development of coronary heart disease, more recent reviews have cast more doubt on this association, placing more of an emphasis on the re-emergence of refined sugars as the main risk factor.[39][40]
    • Research has more clearly shown that trans fat increases the risk of cardiovascular disease, through adverse effects on lipids, endothelial function, insulin resistance, and inflammation.[41] Every 2% of calories consumed from trans fat was associated with a 23% higher CAD risk (RR 1.23, 95% CI 1.11-1.37).[42][18]   
    • A 2016 systemic review revealed that soft drinks and sweetened beverages were associated with a 22% higher risk of myocardial infarction.[43]
    • A 2014 prospective cohort study revealed a 30% and 175% higher chance of cardiovascular disease mortality in the groups who consumed 10 to 24.9% (adjusted hazard ratio 1.30, 95% CI 1.09-1.55) and 25% (adjusted hazard ratio 2.75, 95% CI 1.40-5.42) more calories from added sugar compared with those who consumed less than 10% calories from added sugar.[44] High fructose corn syrup, sucrose, and table sugar have also been reported to play a significant component in coronary artery disease.[45]
    • More recent studies and systematic review articles have focused on red and processed meat consumption.  These articles have revealed a consistently higher risk of coronary heart disease and cardiovascular events ranging from 15 to 29% higher risk with red meat and 23 to 42% higher risk with processed meat consumption.  Most studies included approximately 50 to 100 grams per day of consumption.[46][47][48][49][50][51] Only one of these review articles revealed no significant association between red meat and coronary heart disease (4 studies, RR 1.00 per 100 gram serving per day, 95% CI 0.92-1.46, P=0.25).[46] One article indicated no significant association between processed meats and overall mortality, however, added that the combined intake of red and processed meats was associated with a 23% higher risk (HR 1.23, 95% ci 1.11-1.36) of overall mortality.[51]
  • Sedentary lifestyle: 
    • Exercise is a protective factor in preventing the development of CAD. A 2004 case-control study performed in 52 countries, representing all continents, and involving 15,152 cases and 14,820 controls revealed a population attributable risk of 12.2% that physical inactivity has on myocardial infarction.[52]
    • Several observational studies have shown that individuals who self-select for exercise have lower morbidity and mortality.  Mechanisms for this include enhanced production of endothelial nitrous oxide, more effective deactivation of reactive oxygen species, and improved vasculogenesis. 

In addition to these traditional cardiovascular risk factors, novel risk factors have also been subject to research.  These include:

  • Non-alcoholic fatty liver disease (NAFLD):
    • NAFLD has links to cardiovascular disease.  It is also the most common chronic liver disease in developed countries.[53]
    • A 2017 meta-analysis revealed a 77% higher risk (RR 1.77, 95% CI 1.26-2.48) of cardiovascular events and over double the risk (RR 2.26, 95% CI 1.04-4.92) for coronary artery disease in NAFLD patients.[54]
    • A more recent prospective study revealed that NAFLD patients had greater than double the risk of cardiovascular events.  Patients with liver fibrosis had a four-fold increase.[55]
  • Chronic kidney disease (CKD):
    • CKD has been reported as an independent risk factor for coronary artery disease. Pro-inflammatory mediators, oxidative stress, and decreased nitric oxide production leading to endothelial dysfunction have been reported as possible mechanisms. Silent myocardial infarctions occur more commonly, likely due to the higher incidence of diabetic and uremic neuropathy in CKD patients.[56]
    • CKD, with a GFR of 15-59, is noted as a risk enhancing factor in the American Heart Association Guideline for the Primary Prevention of Cardiovascular Disease.[57]
  • Systemic lupus erythematosus (SLE): 
    • The most common cause of mortality in SLE is cardiovascular disease. There is also a higher prevalence of atherosclerotic cardiovascular disease in these patients. The mechanism is likely a pro-inflammatory effect on coronary microcirculation.[58][59][58] 
    • Pericarditis is a common manifestation of SLE.[60] One case report stated that pericarditis is the most common cardiac manifestation of SLE.[61]
  • Rheumatoid arthritis (RA):
    • Estimates are that RA patients have a 1.5 to 2.0 fold increased risk of coronary artery disease.   Traditional risk factors such as body mass and lipoprotein levels also showed more unpredictable patterns in their predictive accuracy.  The mechanism behind this associated risk is likely through a pro-inflammatory effect.[62]
    • Rheumatoid arthritis is also listed among the risk enhancing factors in the American Heart Association Guideline for the Primary Prevention of Cardiovascular Disease.[57]
  • Inflammatory bowel disease (IBD):
    • A 2017 meta-analysis noted that IBD is associated with a higher risk of coronary artery disease. However, the results were interpreted with caution due to the heterogeneity of the studies. The mechanism of the risk was uncertain, but again, it was thought to be due to a chronic inflammatory state.[63]
  • Human immunodeficiency virus (HIV):
    • HIV is understood to come with a higher risk of cardiovascular disease and its associated sequelae.[64]   
    • A 2018 expert analysis from the American College of Cardiology noted that HIV patients showed a 1.5 to 2-fold increased risk of coronary artery disease. The mechanism, again, was based on a pro-inflammatory state.
  • Thyroid disease:
    • The thyroid gland intricately links to cardiovascular function. Proposed mechanisms include the effect of thyroid hormone on dyslipidemia, cardiac function, atherosclerosis, vascular compliance, and cardiac arrhythmias; this is an area still under study.[65] Guidelines also vary on their screening recommendations for thyroid disease, hypothyroidism, and subclinical hypothyroidism.[66][67]
  • Testosterone:
    • In 2014, the FDA released a required labeling change for low testosterone products for the use of low testosterone due to aging, due to a possible increased risk of heart attack and stroke.  Subsequent studies and reviews have not been consistent in this correlation.  Some reviews have even indicated a potential beneficial cardiovascular effect when treating low testosterone with testosterone supplementation. Further study is needed to provide more clarity on this specific topic.[68][69][70][71][72]
  • Vitamin D
    • Vitamin D has been increasingly studied and debated over the past decade. Vitamin D deficiency has a link with an increased risk of coronary artery disease.[73][74][75][76] Further studies, however, have not confirmed a beneficial effect on Vitamin D supplementation. Further studies are needed to clarify whether Vitamin D supplementation is truly beneficial for coronary artery disease prevention.[77][78][79]

Socioeconomic status:

  • Socioeconomic status is a significant risk factor for cardiovascular disease. Upstream determinants include financial strain, lack of affordable and nutritious food, exposure to domestic violence, and inadequate housing; this is an important consideration to consider given existing cardiovascular disease risk equations do not capture this.[41]  

Women and coronary artery disease (CAD):

  • Although men are at higher risk than women of coronary artery disease, it is still the leading cause of death among women.  Among women, only 54% were aware of this in 2009. Cardiovascular disease caused approximately 1 in 3 female deaths.[80] Women were found to have non-obstructive CAD in 57% of cases, in contrast to men who more commonly had obstructive CAD. Proposed mechanisms for this include coronary microvascular dysfunction (CMD), altered endothelial tone, structural changes, and altered response to vasodilator stimuli.[81] Estrogen is thought to have a protective role in coronary vasoreactivity and is also theorized to promote plaque stabilization via an anti-inflammatory effect on atherosclerosis.[82] 
  • Lack of awareness and understanding of coronary artery disease in women has also led to a disparity in health outcomes. There has been more focus on obstructive CAD and men compared to women.[80][83] One 2012 article reported a decrease in CAD mortality across all age groups in men and an increase in CAD mortality among young women (< 55 years old).[81]

Clinical Significance

Coronary artery disease remains the number one cause of death in the United States.  Given the prevalence of CAD and its risk factors, multi-disciplinary, team-based care may result in significantly improved patient outcomes.[41] Physicians and advanced care clinicians should be aware of screening recommendations and the impact that risk factor mitigation can have on CAD outcomes.  Nurses play a central role in routine screening and education.  Clinical pharmacists play a pivotal role in the pharmacologic management of modifiable risk factors such as hypertension, hyperlipidemia, diabetes, and smoking cessation.  Nutritionists contribute by providing dietary education.  Community outreach by all team members can help mitigate the complex, yet crucial role that socioeconomic status can have on CAD risk and outcomes.  This section will review screening recommendations, the impact of risk factor mitigation on CAD outcomes, aspirin, and new CAD screening tests.  

Hypertension

  • The United States Preventive Services Task Force (USPSTF) gives a grade A recommendation for universal screening for hypertension in patients greater than 18 years of age and a grade I (current evidence insufficient) recommendation for screening for children and adolescents.[84][85]
  • A systolic and diastolic blood pressure reduction of greater than 10mmHg and 5mmHg, respectively, led to a significant absolute risk reduction in CAD-related events (NNT 91).[86]
  • A systolic blood pressure reduction to a goal of 130mmHg reduced the incidence of CAD (NNT 27).[11]
  • A 2002 meta-analysis revealed that systolic blood pressure reduction of 20mmHg and diastolic blood pressure reduction of 10mmHg decreases the risk of death from coronary heart disease by about 50% between ages 40 to 49 and by about 1/3 between ages 80 to 89.[87][88][41]

Hyperlipidemia

  • The USPSTF recommends evaluation for statin use for the primary prevention of cardiovascular disease between 40 to 75 years of age.[89] The USPSTF gives a grade I (current evidence insufficient) recommendation for routine screening for lipid disorders in children and adolescents.[90]
  • In 2011, the National Heart, Lung, and Blood Institute (NHLBI) recommended universal screening between 9 to 11 years of age and again at 17 to 21 years of age.  The American Academy of Pediatrics subsequently endorsed this.  Despite the publication of these guidelines, pediatric lipid screening practice patterns have not followed suit.[91] 
  • An early 1994 review showed that a 10% reduction in serum cholesterol leads to a 50%, 40%, 30%, and 20% drop in CAD risk at age 20, 50, 60, and 70, respectively.[92]
  • The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) study demonstrated that statins reduce the risk of major cardiovascular events.[93] Treatment with a moderate-intensity statin resulted in a CAD absolute risk reduction of 2.7% (NNT 37). Treatment with a high-intensity statin resulted in a 4.1% absolute risk reduction (NNT 24).[11]

Diabetes

  • The USPSTF recommends screening for abnormal glucose in patients aged 40 to 70 years old who are overweight or obese.  Early screening for diabetes can also be a consideration for patients in higher-risk groups. This risk pool includes patients with a family history of diabetes, history of gestational diabetes or polycystic ovarian syndrome, or members of specified racial/ethnic groups (African Americans, American Indians, Alaskan Natives, Asian Americans, Hispanics or Latinos, Native Hawaiians or Pacific Islanders).[94] 
  • The American Diabetes Association states that three years is a reasonable screening interval.
  • A 2019 meta-analysis of 12 cardiovascular outcomes trials indicated that a 0.5% reduction in A1C conferred a 20% hazard risk reduction (95% CI 4-33%) for major cardiovascular events.  This analysis included patients on peptidase-4 inhibitors, GLP-1 agonists, and SGLT-2 inhibitors.[95]

Diet

  • The DASH, Mediterranean, and vegetarian diets have the most evidence for cardiovascular disease prevention.[96] 
  • The DASH diet can reduce systolic blood pressure up to 11.5 mmHg in adults with hypertension.[97][18] A 2013 meta-analysis and systematic review revealed a 21% coronary artery disease risk reduction (RR 0.79, 95% CI 0.71-0.88) with the DASH diet.[98]
  • A 2017 meta-analysis and systematic review revealed an 8% risk reduction (15 studies, RR 0.92, 95% CI 0.90-0.95) of coronary artery disease for every 200 grams per day of fruits and vegetables. This effect was observable at up to 800 grams per day.[99]
  • A 2016 meta-analysis and systematic review revealed a 29% risk reduction (29 studies, RR 0.71, 95% CI 0.63-0.80) of coronary artery disease for every 28 grams per day of nut consumption.[100]
  • A 2017 narrative review revealed a decreased risk of about 20 to 25% with the Mediterranean diet on cardiovascular disease. It was also showed positive effects on endothelin function, arterial stiffness, and cardiac function.[101]
  • The American Heart Association recommends the replacement of saturated fat with polyunsaturated and monounsaturated fats.[102] A 5% exchange in saturated fat consumption with polyunsaturated fat is associated with a 10% lower CAD risk (RR 0.90, 95% CI 0.83-0.97).[103][18] As noted above, a 2018 review, however, challenged the strength of the traditional link between saturated fat and higher CAD risk, compared to other nutrients.[39] In a separate review, the lack of a significant association between saturated fat and cardiovascular disease was due to studies replacing saturated fat with highly refined carbohydrates.  If saturated fats were replaced by polyunsaturated fat, then coronary heart disease is indeed reduced.[40]
  • While it is challenging to carry out research relating to diet practices and coronary artery disease, much research has taken place in the past.[39] The AHA/ACC guidelines recommend a diet consisting mostly of vegetables, fruits, legumes, nuts, whole grains, and fish. Dietary intake of processed meats, refined carbohydrates, and sweetened beverages should be reduced, while avoiding trans fats altogether. Saturated fats should be replaced with polyunsaturated and monounsaturated fats.[102]
  • The USPSTF recommends offering or referring adults who are obese/overweight and have one additional cardiovascular risk factor intensive behavioral counseling to promote a healthful diet and physical activity (Grade B).  The USPSTF also recommends individualizing the decision to offer or refer patients without obesity or other cardiovascular risk factors for behavioral counseling.

Smoking

  • The USPSTF recommends screening for tobacco use in all adults with each clinical encounter and to provide behavioral and pharmacologic smoking cessation interventions.[104] The USPSTF also recommends educating children and adolescents about the risks of smoking to prevent the initiation of tobacco use.[105]
  • The American Heart Association recommends a combined behavioral and pharmacologic approach to maximize quit rates.[41]
  • The risk of coronary artery disease drops to a level of lifetime nonsmokers within four years of quitting, according to the FDA, and within ten years, according to the CDC.[106][107]
  • Behavioral interventions include motivational interviewing (Ask, Advise, Assess, Assist, Arrange for follow-up). 
  • Pharmacologic interventions such as nicotine replacement therapy, varenicline (Chantix), and bupropion (Wellbutrin) reduce cravings and withdrawal symptoms. 
  • A 2014 Cochrane review revealed that nicotine replacement therapies, such as nicotine gum and the nicotine patch increased the chances of smoking cessation by 49% (55 trials, RR 1.49, 95% CI 1.40-1.60) and 64% (43 trials, RR 1.64, 95% CI 1.52-1.78), respectively. The nicotine oral tablets/lozenges (6 trials, RR 1.95, 95% CI 1.61-2.36), inhaler (4 trials, RR 1.90, 95% CI 1.36-2.67), and nasal sprays (4 trials, RR 2.02, 95% CI 1.49-2.73) approximately doubled the chances of success.  The combination of bupropion and nicotine replacement therapy increased the likelihood of success by 24% compared to bupropion alone (4 trials, RR 1.24, 95% CI 1.06-1.45).[108]
  • Varenicline doubled the chances of smoking cessation.[109] There have been rare reports of neuropsychiatric adverse effects with varenicline.  The FDA removed this black box warning in 2016 after noting that the risk was lower than expected.  
  • A 2014 Cochrane review showed that bupropion increases the chances of smoking cessation by 62% (44 trials, N=13,728, RR 1.62, 95% CI 1.48-2.78).[110][102]
  • A 2016 Cochrane review indicated that the combined use of behavioral support and pharmacotherapy had a higher chance of success.[111]

Obesity

  • A patient's body mass index (BMI) should be measured at each clinical encounter. The USPSTF recommends that practitioners offer obese adults a referral to a multicomponent behavioral interventionist.[112]
  • There is a large amount of evidence showing that in obese or overweight patients, even just a modest 5% body weight loss can lead to clinically significant health benefits.[113]

Exercise

  • The USPSTF recommends patients who are overweight, obese, or have CAD risk factors to intensive behavioral counseling for interventions to promote physical activity for the prevention of CAD.[18][114][115]
  • According to the National Health Interview Survey, only 20.9% of adults met the 2008 federal physical activity guidelines for aerobic and strengthening activity.[18]
  • Approximately 150 minutes per week of moderate-intensity aerobic activity reduces the risk of cardiovascular disease.[116] Moderate-intensity aerobic exercise is defined as 50 to 70 percent of the patient's maximum heart rate (220 beats per minute minus the patient's age).  Any amount of physical activity has shown to have benefits in reducing CAD risk.[102][117] The most active patients have an approximately 35 to 40 percent risk reduction for coronary artery disease.  
  • The AHA/ACC guidelines also recommend resistance strength training to be incorporated into regular physical activity, as this can help improve physical function and ability to exercise.[102][118]

Aspirin in primary prevention: 

  • Aspirin has long played a role in atherosclerotic cardiovascular disease prevention.  Although still established for secondary prevention, its use in primary prevention has more recently come into question due to a less favorable risk-benefit ratio [57].  Recent evidence suggested a more tailored approach to the use of aspirin [119]
  • The USPSTF recommends aspirin for patients age 50 to 59 years of age, with a 10-year atherosclerotic cardiovascular disease risk, and do not have bleeding risk factors. Aspirin may be considered for those 60 to 69 years of age but may have less overall benefit and higher bleeding risk.[120]

New CAD screening tests:

Coronary artery calcium (CAC) score:

  • CAC is an established non-invasive screening test for coronary artery disease.  It involves a non-contrast CT of the heart, and totals identified coronary artery calcium, a component of atherosclerosis. 
  • A large prospective cohort study found that CAC improved the detection of at-risk patients for having a coronary event to better match statin therapy with appropriate patients.[121]
  • The 2019 AHA/ACC primary prevention guideline recommends CAC for those who are at intermediate-risk (10-year >/=7.5% to <20%) or selected borderline risk (10-year ASCVD risk 5-<7.5%) patients.  CAC score can help patients who desire more information before starting pharmacotherapy.  If the CAC score is zero, then the patient does not require a statin as long as the patient does not smoke, have diabetes mellitus, or have a family history of premature clinical ASCVD.  If CAC is 1 to 99,  a statin is favored in patients aged 55-years old and greater.  If the CAC is 100 or in the 75th percentile or higher, then statin treatment is favored.[57]
  • The 2017 SCCT (Society of Cardiovascular Computed Tomography) guideline recommends shared-decision making and CAC consideration for those who are 5 to 20% 10-year ASCVD risk or < 5% 10-year ASCVD risk who have another strong indication such as those with a family history of premature CAD.[122]

Carotid intimal medial thickness (CIMT):

  • CIMT is another proposed tool for non-invasive risk stratification for CAD. This assessment is accomplished predominantly by ultrasound, but may also use MRI. There has been conflicting data from several large studies regarding this modality, most likely due to non-standard image acquisition and analysis as well as study design differences.[123]
  • A 2012 meta-analysis combining CIMT and Framingham Risk Score (FRS) did not substantially improve risk prediction.[124]
  • The AHA/ACC changed its stance from class IIa recommendation for its use in intermediate-risk patients in 2010 to recommend against its use in a 2013 update.[125][126]
  • More recently, a 2017 observational multi-ethnic study of atherosclerosis (MESA) found that the combination of CIMT and positive CAC improved prediction of cardiovascular risk.[127]

Flow-mediated dilation (FMD) and endothelin function: 

  • FMD is another proposed test that can potentially predict cardiovascular risk by measuring the health of blood vessel endothelial function. Physiologic and pharmacologic stress, such as hypertension, smoking, or certain medications, can alter this.  
  • There are different methods to measure FMD. Protocols involving vasoactive agents via coronary catheterization is a more direct measurement of the coronary artery endothelial function, more specifically referred to as coronary flow reserve (CFR).[128]

  • Brachial artery flow-mediated dilation and reactive hyperemia-peripheral arterial tonometry (RH-PAT) are more peripheral measurements. A 2015 meta-analysis conferred that these two methods demonstrated similar prognostic value on cardiovascular outcomes. Additional research is necessary to determine whether this screening strategy can improve cardiovascular outcomes.[129]

Novel biomarkers:

  • A 2017 article reviewed novel potential biomarkers for CAD, such as fibrinogen, hs-CRP, Lipoprotein-associated PA2, Lipoprotein A, hs-troponin, NT-proBNP, and Cystatin C.  None met all necessary criteria to be considered an ideal biomarker.[130]

Enhancing Healthcare Team Outcomes

Coronary artery disease is the leading cause of death in the United States and many countries worldwide. Given the prevalence of CAD and its risk factors, multi-disciplinary, team-based care may result in significantly improved patient outcomes. Clinicians, nurses, and pharmacists need to remain abreast of the most current research and work together as an interprofessional team to encourage the following long-term treatment recommendations and regular exercise to obtain the best patient outcomes. [Level 5]

Nursing, Allied Health, and Interprofessional Team Interventions

The first portion of the encounter identifies the patient's age, gender, ethnicity, and past medical history. Detection of CAD risk factors can occur within the first 5 minutes of the clinical encounter.  Vital signs detect elevated blood pressures and excessive weight. Diet and physical activity can also be discussed. Early education on lifestyle modifications can improve outcomes and mitigate risk factors. Screening recommendations can also be provided. 

"The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, Department of the Air Force, Department of Defense, or the U.S. government. This document was created free of branding or market affiliations.  The author is operating solely as a contributor." 


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