Risk Factors for Coronary Artery Disease
- Author: F Brian Boudi, MD, FACP; Chief Editor: Yasmine Subhi Ali, MD, FACC, FACP, MSCI more...
Risk factors for coronary artery disease (CAD) were not formally established until the initial findings of the Framingham Heart Study in the early 1960s. The understanding of such factors is critical to the prevention of cardiovascular morbidities and mortality. See the image below.
Risk factors for coronary artery disease
Conventional risk factors
Older age: Over age 45 years in men and over age 55 years in women
Family history of early heart disease
Race: Among persons with CAD, the cardiovascular death rate for African Americans is reported to be particularly high; in Asians, low levels of high-density lipoprotein cholesterol (HDL-C), which are considered to be a risk factor for coronary heart disease, appear to be especially prevalent; South Asians appear to have a higher independent risk for cardiovascular disease as well.
Modifiable risk factors
High blood cholesterol levels (specifically, low-density lipoprotein cholesterol [LDL-C])
High blood pressure
Cigarette smoking: Cessation of cigarette smoking constitutes the single most important preventive measure for CAD
Diabetes mellitus 
Lack of physical activity
Mental stress and depression
Nontraditional or novel risk factors
High levels of the following are considered to be risk factors for CAD:
C-reactive protein (CRP): High levels are related to the presence of inflammation and, according to some research results, may be associated with an increased risk of CAD development and heart attack 
Homocysteine: In the general population, mild to moderate elevations are due to insufficient dietary intake of folic acid, but homocysteine levels may also identify people at increased risk for heart disease
Small, dense LDL-C particles
Various medical conditions that can contribute to CAD include the following:
End-stage renal disease (ESRD)
Chronic inflammatory diseases affecting connective tissues (eg, lupus, rheumatoid arthritis) [3, 4]
Human immunodeficiency virus (HIV) infection (acquired immunodeficiency syndrome [AIDS], highly active antiretroviral therapy [HAART]) 
Xanthelasmata (raised yellow patches around the eyelids)
The following are also considered to be risk factors:
Tissue plasminogen activator (tPA): An imbalance of the clot dissolving enzymes (eg, tPA) and their respective inhibitors (plasminogen activator inhibitor-1 [PAI-1]) may predispose individuals to myocardial infarctions
Low serum testosterone levels: Have a significant negative impact on patients with CAD
Hysterectomy: A study suggests that this becomes a risk factor later in life in women who have the surgery at or before age 50 years
Lack of sleep
Identifying coronary artery disease
Direct plaque imaging
Electron-beam computed tomography (EBCT) scanning: To identify coronary calcification; can reveal at-risk individuals and perhaps allow for medical monitoring 
64-slice CT angiography: Bulky plaques may be identified in asymptomatic patients; the risk-benefit of using CT angiography in an asymptomatic patient for the identification of atherosclerotic plaques is still a subject of much debate
Carotid intima-media thickness (IMT), pulse wave velocity (PWV), and the ankle-brachial index (ABI): Widely used, noninvasive modalities for evaluating atherosclerosis
In a 10-year comparison of 10 biomarkers for predicting death and major cardiovascular events in approximately 3000 individuals, the most informative biomarkers for predicting death were as follows:
B-type natriuretic peptide (BNP)
Urinary albumin-to-creatinine ratio
The most informative biomarkers for predicting major cardiovascular events were BNP and the urinary albumin-to-creatinine ratio.
Risk Factor Biomarkers
Risk factors for coronary artery disease (CAD) were not formally established until the initial findings of the Framingham Heart Study in the early 1960s. The understanding of such factors and risk stratification is critical for a clinician to prevent cardiovascular morbidities and mortality.[7, 8, 9] See the image below for traditional and nontraditional risk factor biomarkers.
For more information see Coronary Artery Disease.
Conventional Risk Factors
Many traditional risk factors for coronary artery disease (CAD) are related to lifestyle, and preventative treatment can be tailored to modifying specific factors.
The risk of developing CAD increases with age, and includes age greater than 45 years in men and greater than 55 years in women.
A family history of early heart disease is also a risk factor, including heart disease in the father or a brother diagnosed before age 55 years and in the mother or a sister diagnosed before age 65 years.
The prospective, observational Reduction of Atherothrombosis for Continued Health (REACH) registry, a large international study of individuals with atherothrombotic disease, documented ethnic-specific differences in cardiovascular risk factors and variations in cardiovascular mortality worldwide. The study found that although prevalence of traditional atherothrombotic risk factors widely varied among the ethnic and racial groups, the use of medical therapies to reduce risk was comparable among all groups. At 2-year follow-up, the rate of cardiovascular death was significantly higher in blacks, and cardiovascular death rates were significantly lower in the Asian groups.
Results from the Atherosclerosis Risk in Communities (ARIC) study suggest that lipoprotein(a) levels are positively associated with cardiovascular disease events, and that these associations were at least as strong, with a larger range of lipoprotein(a) concentrations, in blacks compared with whites.
One meta-analysis by Huxley et al suggests that isolated low high-density lipoprotein cholesterol (HDL-C) is a novel lipid phenotype that appears to be more prevalent among Asian populations; this phenotype also increases the risk of coronary heart disease in the Asian population.
The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have produced guidelines for the procedures of detection, management, or prevention of cardiovascular disease. One set of recommendations focuses on cardiovascular risk in asymptomatic results, and these recommendations are discussed below.
For all asymptomatic adults, global risk scoring should be performed and a family history of cardiovascular disease should be obtained for cardiovascular risk assessment.
The ACCF/AHA 2010 guideline does not recommend the following measures for coronary heart disease risk assessment in asymptomatic adults:
Measurement of lipid parameters beyond a standard fasting lipid profile (A standard fasting lipid profile is recommended as part of global risk scoring.)
Brachial/peripheral arterial flow-mediated dilation studies
Specific measures of arterial stiffness
Coronary computed tomography angiography
MRI for detection of vascular plaque
Other tests and measures for cardiovascular risk assessment in asymptomatic adults are recommended as reasonable, might be reasonable, or may be considered for specific patient populations and risk levels:
A resting electrocardiogram (ECG) is reasonable for asymptomatic adults with hypertension or diabetes and may be considered in asymptomatic adults without hypertension or diabetes.
An exercise ECG may be considered in intermediate-risk asymptomatic adults (including sedentary adults considering starting a vigorous exercise program), particularly when attention is paid to non-ECG markers such as exercise capacity.
Transthoracic echocardiography to detect left ventricular hypertrophy may be considered for asymptomatic adults with hypertension but is not recommended in asymptomatic adults without hypertension.
Stress echocardiography is not indicated for low- or intermediate-risk asymptomatic adults.
Coronary artery calcium (CAC) measurement is reasonable for asymptomatic intermediate-risk adults,  but it should not be performed for persons at low risk; it may be reasonable when the patient’s risk falls between low and intermediate.
MRI among asymptomatic individuals with regional myocardial dysfunction (RMD) is an independent predictor beyond traditional risk factors and global left ventricle (LV) assessment for incident heart failure and atherosclerotic cardiovascular events. 
The Heart and Estrogen/progestin Replacement Study evaluated the effects of hormone replacement therapy on cardiovascular events among 2763 postmenopausal women with CAD. Sudden cardiac death comprised most cardiac deaths among these postmenopausal women. Independent predictors of sudden cardiac death included myocardial infarction, congestive heart failure, an estimated glomerular filtration rate of less than 40 mL/min/1.73 m 2, atrial fibrillation, physical inactivity, and diabetes. These risk factors should be considered when left ventricular ejection fraction (LVEF) is present. 
Modifiable Risk Factors
Odegaard et al suggest that an increasing number of protective lifestyle factors are associated with a marked decrease in risk of coronary heart disease, cerebrovascular disease, and overall CVD mortality in Chinese men and women. Protective lifestyle factors included dietary pattern, physical activity, alcohol intake, usual sleep, smoking status, and body mass index.
High blood cholesterol levels
The Framingham Heart Study results demonstrated that the higher the cholesterol level, the greater the risk of coronary artery disease (CAD); alternatively, CAD was uncommon in people with cholesterol levels below 150 mg/dL. In 1984, the Lipid Research Clinics-Coronary Primary Prevention Trial revealed that lowering total and LDL or bad cholesterol levels significantly reduced CAD. More recent series of clinical trials using statin drugs have provided conclusive evidence that lowering LDL cholesterol reduces the rate of myocardial infarction (MI), the need for percutaneous coronary intervention and the mortality associated with CAD-related causes.
High blood pressure
Of the 50 million Americans with hypertension, almost one third evade diagnosis and only one fourth receive effective treatment. In the Framingham Heart Study, even high-normal blood pressure (defined as a systolic blood pressure of 130-139 mm Hg, diastolic blood pressure of 85-89 mm Hg, or both) increased the risk of cardiovascular disease 2-fold, as compared with healthy individuals.
A study by Allen et al found that people who have increases or decreases in blood pressure during middle age have associated higher and lower remaining lifetime risk for cardiovascular disease. This suggests that prevention efforts should continue to emphasize the importance of lowering blood pressure in order to avoid hypertension.
The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) emphasizes weight control; adoption of the Dietary Approaches to Stop Hypertension (DASH) diet, with sodium restriction and increased intake of potassium and calcium-rich foods; moderation of alcohol consumption to less than 2 drinks daily; and increased physical activity.
A meta-analysis performed by Nordmann et al found that the Mediterranean diet had more favorable changes in weighted mean differences of body weight, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol, and high-sensitivity C-reactive protein than low-fat diets.
A randomized controlled trial indicated that soy and milk protein intake reduce systolic blood pressure compared with a high-glycemic-index refined carbohydrate among patients with prehypertension and stage 1 hypertension. This suggests that partially replacing carbohydrate with soy or milk protein is a good intervention and treatment for hypertension.
Hypertension, along with other factors such as obesity, have been said to contribute to the development of left ventricular hypertrophy (LVH). LVH has been found to be an independent risk factor to cardiovascular disease morbidity and mortality. It roughly doubles the risk of cardiovascular death in both men and women.
Cessation of cigarette smoking constitutes the single most important preventive measure for CAD. As early as the 1950s, studies reported a strong association between cigarette smoke exposure and heart disease. Persons who consume more than 20 cigarettes daily have a 2- to 3-fold increase in total heart disease. Continued smoking is a major risk factor for recurrent heart attacks.
Smoking is a risk factor for CVD in women and men; however, a systematic review and meta-analysis by Huxley and Woodward suggests that in some countries, smoking by women is on the rise; the study suggests that proper counseling and nicotine addiction programs should focus on young women.
A disorder of metabolism, diabetes mellitus causes the pancreas to produce either insulin deficiency or insulin resistance. Glucose builds up in the blood stream, overflows through the kidneys into the urine, and results in the body losing its main source of energy, even though the blood contains large amounts of glucose.
An estimated 20.8 million people in the United States (7% of the population) have diabetes; 14.6 million have been diagnosed, and 6.2 million have not yet been diagnosed. Diabetes prevalence figures (including diagnosed and undiagnosed diabetes) are available at the Centers for Disease Control and Prevention (CDC).
Patients with diabetes are 2-8 times more likely to experience future cardiovascular events than age-matched and ethnically matched individuals without diabetes, and a recent study suggested a potential reduction of all-cause and cardiovascular disease–specific mortality in women with diabetes mellitus who consumed whole-grain and bran. Another study suggested that meat consumption is associated with a higher incidence of coronary heart disease and diabetes mellitus.
Paynter et al found significant improvements in predictive ability of CVD risk using models incorporating HbA1c levels compared with classification of diabetes in both men and women.
Obesity is associated with elevated vascular risk in population studies. In addition, this condition has been associated with glucose intolerance, insulin resistance, hypertension, physical inactivity, and dyslipidemia.[32, 33]
A study by Das et al examined more than 50,000 patients from the National Cardiovascular Data Registry with STEMI. The results suggest that although patients who are extremely obese (body mass index [BMI] >40) present at a younger age with STEMI, they have less extensive coronary artery disease and better LV function. However, as expected, their in-hospital mortality following STEMI is increased (adjusted odds ratio, 1.64).
Lack of physical activity
The cardioprotective benefits of exercise include reducing adipose tissue, which decreases obesity; lowering blood pressure, lipids, and vascular inflammation; improving endothelial dysfunction, improving insulin sensitivity, and improving endogenous fibrinolysis. In addition, regular exercise reduces myocardial oxygen demand and increases exercise capacity, translating into reduced coronary risk. In the Women's Health Initiative study, walking briskly for 30 minutes, 5 times per week, was associated with a 30% reduction in vascular events during a 3.5-year follow-up period. Studies have also shown that even 15 minutes a day or 90 minutes a week of moderate-intensity exercise may be beneficial. Adherence to a healthy lifestyle is associated with a low risk of sudden cardiac death among women.
Evidence suggests that screen-based entertainment (television or other “screen time”) increases the risk of cardiovascular disease, regardless of physical activity. The relationship between inflammatory and metabolic risk factors may partly explain this relationship.
Metabolic syndrome is characterized by a group of medical conditions that places people at risk for both heart disease and type 2 diabetes mellitus. In the Kuopio Ischemic Heart Disease Risk Factor Study, patients with metabolic syndrome had significantly higher rates of coronary, cardiovascular, and all-cause mortality.
People with metabolic syndrome have 3 of the following 5 traits and medical conditions, as defined by the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) Cholesterol Education Program (CEP) :
Elevated waist circumference - Waist measurement of 40 inches or more in men, 35 inches or more in women
Elevated levels of triglycerides - 150 mg/dL or higher or taking medication for elevated triglyceride levels
Low levels of HDL (high-density lipoprotein) or good cholesterol - Below 40 mg/dL in men, below 50 mg/dL in women, or taking medication for low HDL cholesterol level
Elevated blood pressure levels - For systolic blood pressure, 130 mm Hg or higher; 85 mm Hg or higher for diastolic blood pressure; or taking medication for elevated blood pressure levels
Elevated fasting blood glucose levels - 100 mg/dL or higher or taking medication for elevated blood glucose levels  (Note: The American Association of Clinical Endocrinologists, the International Diabetes Federation, and the World Health Organization have other, similar, definitions for metabolic syndrome.)
Although high consumption of carbohydrates and sugar is associated with higher rates of cardiovascular disease risk in adults, not much is known about the effect of added sugars in US adolescents. A study of the National Health and Nutrition Examination Survey (NHANES) 1999-2004, suggests that added sugar consumption is positively associated with an increase risk of cardiovascular disease in adolescents. The results of this study suggest that future risk of cardiovascular disease may be reduced by minimizing sugar intake.
A meta-analysis of multiple population studies associated chocolate consumption with a substantial risk reduction (approximately 30%) in cardiometabolic disorders, including coronary disease, cardiac deaths, diabetes, and stroke. The apparent benefits of chocolate may accrue from a beneficial impact of polyphenols present in cocoa products that increase the bioavailability of nitric oxide. These findings are based on observational studies, and further experimental studies are warranted to confirm the finding of a potential beneficial effect of chocolate consumption.
Mental stress, depression, cardiovascular risk
Depression has been strongly implicated in predicting CAD . Adrenergic stimulation during stress can increase myocardial oxygen requirements, can cause vasoconstriction, and has been linked to platelet and endothelial dysfunction and metabolic syndrome.
Shah et al found that in adults younger than 40 years, depression and history of attempted suicide are significant independent predictors of premature cardiovascular disease and ischemic heart disease mortality in both males and females.
Nontraditional or Novel Risk Factors
C-reactive protein (CRP) is a protein in the blood that demonstrates the presence of inflammation, which is the body's response to injury or infection; CRP levels rise if inflammation is present. The inflammation process appears to contribute to the growth of arterial plaque, and in fact, inflammation characterizes all phases of atherothrombosis and is actively involved in plaque formation and rupture.
According to some research results, high blood levels of CRP may be associated with an increased risk of developing coronary artery disease (CAD) and having a heart attack.[2, 9] In the Jupiter trial, in healthy persons without hyperlipidemia but with elevated high-sensitivity CRP levels, the statin drug rosuvastatin significantly reduced the incidence of major cardiovascular events.
The 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults states that measurement of C-reactive protein can be useful in selecting patients for statin therapy and may be reasonable for cardiovascular risk assessment, depending on the patient’s age and risk level. C-reactive protein measurement is not recommended for cardiovascular risk assessment in asymptomatic high-risk adults, low-risk men 50 years or younger, or low-risk women 60 years or younger.
An elevated lipoprotein(a) [Lp(a)] level is an independent risk factor of premature CAD and is particularly a significant risk factor for premature atherothrombosis and cardiovascular events. Measurement of Lp(a) is more useful for young individuals with a personal or family history of premature vascular disease and repeat coronary interventions. The 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults states that, in asymptomatic intermediate-risk adults, lipoprotein-associated phospholipase A2 might be reasonable for cardiovascular risk assessment.
Lp(a) may be used to identify people at increased cardiovascular risk, but as of yet, there have been no studies on Lp(a) lowering because of the lack of available agents that are effective in reducing this value. Therefore, low-density lipoprotein (LDL) lowering is probably the best strategy in people with elevated Lp(a) levels.
In patients with genetically confirmed heterozygous familial hypercholesterolemia, the presence of elevated levels of lipoprotein(a), hypertension, and renal insufficiency appear to be independent predictors of CAD beyond elevated pretreatment low-density lipoprotein (LDL)-cholesterol.
Homocysteine is a natural by-product of the dietary breakdown of protein methionine. In the general population, mild to moderate elevations are due to insufficient dietary intake of folic acid. Homocysteine levels may identify people at increased risk of heart disease, but again, due to the lack of agents that effectively alter the homocysteine levels, studies have not shown any benefit from lowering the homocysteine level.
Tissue plasminogen activator
An imbalance of the clot dissolving enzymes (eg, tissue plasminogen activator [tPA]) and their respective inhibitors (plasminogen activator inhibitor-1 [PAI-1]) may predispose individuals to myocardial infarctions.
Small, Dense LDL
Individuals with a predominance of small, dense LDL particles are at increased risk for CAD. Thus, core lipid composition and lipoprotein particle size and concentration may provide a better measure of cardiovascular risk prediction.
One study suggests that the risk of coronary heart disease contributed by LDL appeared to result to a large extent from LDL that contains apolipoprotein C-III.
Levels of fibrinogen, an acute-phase reactant, increase during an inflammatory response. This soluble protein is involved in platelet aggregation and blood viscosity, and it mediates the final step in clot formation. Significant associations were found between fibrinogen level and risk of cardiovascular events in the Gothenburg, Northwick Park, and Framingham heart studies.
Medical conditions such as end-stage renal disease (ESRD), chronic inflammatory diseases affecting connective tissues (eg, lupus, rheumatoid arthritis),[3, 4] human immunodeficiency virus (HIV) infection (acquired immunodeficiency syndrome [AIDS], highly active antiretroviral therapy [HAART]), and other markers of inflammation have all been widely reported to contribute to the development of CAD.
ESRD is associated with anemia, hyperhomocysteinemia, increased calcium phosphate product, calcium deposits, hypoalbuminemia, increased troponin, increased markers of inflammation, increased oxidant stress, and decreased nitric oxide activity factors, all of which may contribute to increased CAD risk.
The 2010 ACCF/AHA recommendations note that urinalysis to detect microalbuminuria is reasonable for cardiovascular risk assessment in asymptomatic adults with hypertension or diabetes, and might be reasonable for cardiovascular risk assessment in asymptomatic intermediate-risk adults without hypertension or diabetes.
Low serum testosterone levels have a significant negative impact on patients with CAD. More studies are needed to assess better treatment. One meta-analysis suggests that the presence of erectile dysfunction increases the risk of cardiovascular disease, coronary heart disease, stroke, and all-cause mortality. This additional risk may be independent of conventional cardiovascular risk factors.
One study suggests women aged 50 years or younger who undergo a hysterectomy are at an increased risk for cardiovascular disease later in life. Oophorectomy also increases the risk for both coronary heart disease and stroke.
A systemic review and meta-analysis by Cappuccio et al suggests that too little sleep (≤5-6 h per night) or too much sleep (>8-9 h per night) increases risk of coronary heart disease. Too little sleep is also associated with an increased risk of stroke. The association between sleep and cardiac events is consistent across different populations.
A population-based study by Laugsand et al found that insomnia is associated with a moderately increased risk of acute myocardial infarction.
Oberg et al suggest an association between birth weight and risk of cardiovascular disease within disease-discordant dizygotic twins but not monozygotic twins. This could be a result of common cause factors that vary within dizygotic but not monozygotic twin pairs, which may help identify them.
The Copenhagen City Heart Study found that xanthelasmata (raised yellow patches around the eyelids) but not arcus corneae (white or grey rings around the cornea) constitutes an independent risk factor for cardiovascular disease. Presence of xanthelasmata indicated increased risk for myocardial infarction, ischemic heart disease, and severe atherosclerosis.
A prospective cohort study (n=2312) by Kestenbaum et al evaluated older patients without CAD over 14 years. Vitamin D and parathyroid hormone (PTH) were measured, and the outcomes included myocardial infarction, heart failure, cardiovascular death, and all-cause mortality. Vitamin D deficiency was associated with increased mortality and myocardial infarction (each 10 ng/mL drop in vitamin D was associated with 9% greater increase in death and 25% increase in MI). PTH excess was associated with a 30% increased risk of heart failure. Further randomized controlled trials are required.
Identifying Coronary Artery Disease
Direct plaque imaging
Studies indicate that using electron-beam computed tomography (EBCT) scanning to identify coronary calcification can reveal at-risk individuals and perhaps allow for medical monitoring. With the advent of new 64-slice CT angiography, bulky plaques may be identified in asymptomatic patients.
The risk benefit of using CT angiography in an asymptomatic patient for the identification of atherosclerotic plaques is still a subject of much debate. The negative predictive value of CT angiography, however, is very high. CAD identified by CT angiography has significant prognostic implications.
Carotid intima-media thickness (IMT), pulse wave velocity (PWV), and the ankle-brachial index (ABI) are widely used noninvasive modalities for evaluating atherosclerosis.
Polak et al suggest the maximum intima-media thickness of the internal carotid artery along with the presence of plaque significantly but modestly improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort.
One study suggested regression or slow progression of carotid IMT due to cardiovascular drug therapies does not reduce cardiovascular events.
The 2010 ACCF/AHA guideline states that measurement of carotid intima-media thickness is reasonable for cardiovascular risk assessment in asymptomatic intermediate-risk adults, provided that published recommendations on equipment, method, and training are carefully followed. The guideline also states that in asymptomatic intermediate-risk adults, measurement of ankle-brachial index is reasonable for cardiovascular risk assessment.
Other potential risk factors for developing CAD have yet to be defined. However, as data are deciphered from the human genome project, the list of genetic contributors to CAD should greatly increase.
For patients without diabetes and known CAD, a noninvasive, whole-blood test based on gene expression and demographic characteristics may be beneficial in assessment of obstructive CAD.
The 2010 ACCF/AHA guideline does not recommend genotype testing for coronary heart disease risk assessment in asymptomatic adults.
In a 10-year comparison of 10 biomarkers for predicting death and major cardiovascular events in approximately 3000 individuals, the most informative biomarkers for predicting death were blood levels of B-type natriuretic peptide (BNP), CRP, homocysteine, renin, and the urinary albumin-to-creatinine ratio. The most informative biomarkers for predicting major cardiovascular events were BNP and the urinary albumin-to-creatinine ratio.
The 2010 ACCF/AHA guideline does not recommend measurement of natriuretic peptides for coronary heart disease risk assessment in asymptomatic adults.
Cystatin C (Cys-C) has been proposed as an indicator of renal dysfunction that is associated with cardiovascular events and it has shown to be a good predictor of long-term mortality in patients with normal renal function.
Individuals with elevated multimarker scores had a 4-fold higher risk of death and an almost 2-fold higher risk of major cardiovascular events relative to those with low multimarker scores. However, the investigators reported that the use of multiple biomarkers added only moderately to the overall prediction of risk based on conventional cardiovascular risk factors, as evidenced by small changes in the C-statistic.
Measurement of HDL cholesterol should be used as part of the initial cardiovascular risk assessment but should not be used as a predictive tool of residual vascular risk in patients who are treated with potent high-dose statin therapy to lower LDL cholesterol.
Risk Assessment Guidelines
In November 2013, The American College of Cardiology (ACC) and the American Heart Association (AHA) released updated risk-assessment guidelines for atherosclerotic cardiovascular disease. Changes and recommendations include the following.[69, 70]
Stroke is added to the list of coronary events traditionally covered by risk prediction equations
The guidelines focus primarily on the 10-year risk of atherosclerosis-related events; they focus secondarily on the assessment of lifetime risk for adults aged 59 or younger without high shorter-term risk
The strongest predictors of 10-year risk are identified as age, sex, race, total cholesterol, high-density lipoprotein cholesterol (HDL-C), blood pressure, blood-pressure treatment status, diabetes, and current smoking status
Adjunct formulas for refining risk estimates by gender and race are provided
If risk prediction needs to be further sharpened after risk prediction equations have been performed, the guidelines indicate that coronary-artery calcium scores, family history, high-sensitivity C-reactive protein, and the ankle-brachial index can be used
The guidelines recommend that statin therapy be considered in individuals whose 10-year atherosclerotic cardiovascular disease event risk is 7.5% or greater
Guidelines from the American Heart Association and the American College of Cardiology (AHA/ACC) recommend use of a revised calculator for estimating the 10-year risk of developing a first atherosclerotic cardiovascular disease (ASCVD) event, which is defined as a nonfatal myocardial infarction, death from coronary heart disease, or stroke (fatal or nonfatal) in a person who was initially free from ASCVD.[69, 70] The calculator incorporates the following risk factors:
Systolic blood pressure
Treatment for elevated blood pressure
For patients 20-79 years of age who do not have existing clinical ASCVD, the guidelines recommend assessing clinical risk factors every 4-6 years. For patients with low 10-year risk (< 7.5%), the guidelines recommend assessing 30-year or lifetime risk in patients 20-59 years old.
Regardless of the patient’s age, clinicians should communicate risk data to the patient and refer to the AHA/ACC lifestyle guidelines, which cover diet and physical activity. For patients with elevated 10-year risk, clinicians should communicate risk data and refer to the AHA/ACC guidelines on blood cholesterol and obesity.
Yeboah J, Erbel R, Delaney JC, et al. Development of a new diabetes risk prediction tool for incident coronary heart disease events: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study. Atherosclerosis. 2014 Aug 14. 236(2):411-417. [Medline].
Arroyo-Espliguero R, Avanzas P, Cosin-Sales J, Aldama G, Pizzi C, Kaski JC. C-reactive protein elevation and disease activity in patients with coronary artery disease. Eur Heart J. 2004 Mar. 25(5):401-8. [Medline].
Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997 Mar 1. 145(5):408-15. [Medline].
Chung CP, Oeser A, Raggi P, et al. Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum. 2005 Oct. 52(10):3045-53. [Medline].
Sani MU. Myocardial disease in human immunodeficiency virus (HIV) infection: a review. Wien Klin Wochenschr. 2008. 120(3-4):77-87. [Medline].
Keelan PC, Bielak LF, Ashai K, et al. Long-term prognostic value of coronary calcification detected by electron-beam computed tomography in patients undergoing coronary angiography. Circulation. 2001 Jul 24. 104(4):412-7. [Medline].
Heart Disease and Stroke Statistics -- 2009 Update. American Heart Association. Available at http://www.americanheart.org/presenter.jhtml?identifier=3000090 \t _blank. Accessed: September 10, 2009.
Howard BV, Rodriguez BL, Bennett PH, Harris MI, Hamman R, Kuller LH, et al. Prevention Conference VI: Diabetes and Cardiovascular disease: Writing Group I: epidemiology. Circulation. 2002 May 7. 105(18):e132-7. [Medline].
Qureshi WT, Rana JS, Yeboah J, Bin Nasir U, Al-Mallah MH. Risk stratification for primary prevention of coronary artery disease: roles of C-reactive protein and coronary artery calcium. Curr Cardiol Rep. 2015 Dec. 17 (12):110. [Medline].
Mack M, Gopal A. Epidemiology, traditional and novel risk factors in coronary artery disease. Heart Fail Clin. 2016 Jan. 12 (1):1-10. [Medline].
Cohen R, Budoff M, McClelland RL, et al. Significance of a positive family history for coronary heart disease in patients with a zero coronary artery calcium score (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol. 2014 Oct 15. 114(8):1210-4. [Medline].
Meadows TA, Bhatt DL, Cannon CP, et al. Ethnic differences in cardiovascular risks and mortality in atherothrombotic disease: insights from the Reduction of Atherothrombosis for Continued Health (REACH) registry. Mayo Clin Proc. 2011 Oct. 86(10):960-7. [Medline]. [Full Text].
Virani SS, Brautbar A, Davis BC, et al. Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2012 Jan 17. 125(2):241-9. [Medline].
Huxley RR, Barzi F, Lam TH, et al. Isolated low levels of high-density lipoprotein cholesterol are associated with an increased risk of coronary heart disease: an individual participant data meta-analysis of 23 studies in the Asia-Pacific region. Circulation. 2011 Nov 8. 124(19):2056-64. [Medline].
Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006 Dec 21. 355(25):2631-9. [Medline].
Gang L, Wei-Hua L, Rong A, Jian-Hong Y, Zi-Hua Z, Zhong-Zhi T. Serum gamma-glutamyltransferase levels predict the progression of coronary artery calcification in adults with type 2 diabetes mellitus. Angiology. 2015 Aug. 66(7):667-74. [Medline].
Yan RT, Bluemke D, Gomes A, et al. Regional left ventricular myocardial dysfunction as a predictor of incident cardiovascular events MESA (multi-ethnic study of atherosclerosis). J Am Coll Cardiol. 2011 Apr 26. 57(17):1735-44. [Medline].
Deo R, Vittinghoff E, Lin F, et al. Risk factor and prediction modeling for sudden cardiac death in women with coronary artery disease. Arch Intern Med. 2011 Oct 24. 171(19):1703-9. [Medline].
Odegaard AO, Koh WP, Gross MD, Yuan JM, Pereira MA. Combined lifestyle factors and cardiovascular disease mortality in Chinese men and women: the Singapore Chinese health study. Circulation. 2011 Dec 20. 124(25):2847-54. [Medline].
LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005 Apr 7. 352(14):1425-35. [Medline].
Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21. 289(19):2560-72. [Medline].
Vasan RS, Larson MG, Leip EP, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001 Nov 1. 345(18):1291-7. [Medline].
Allen N, Berry JD, Ning H, et al. Impact of blood pressure and blood pressure change during middle age on the remaining lifetime risk for cardiovascular disease: the cardiovascular lifetime risk pooling project. Circulation. 2012 Jan 3. 125(1):37-44. [Medline].
Nordmann AJ, Suter-Zimmermann K, Bucher HC, et al. Meta-analysis comparing mediterranean to low-fat diets for modification of cardiovascular risk factors. Am J Med. 2011 Sep. 124(9):841-851.e2. [Medline].
Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990 May 31. 322(22):1561-6. [Medline].
Rea TD, Heckbert SR, Kaplan RC, et al. Smoking status and risk for recurrent coronary events after myocardial infarction. Ann Intern Med. Sep 17 2002. 137(6):494-500.
Huxley RR, Woodward M. Cigarette smoking as a risk factor for coronary heart disease in women compared with men: a systematic review and meta-analysis of prospective cohort studies. Lancet. 2011 Oct 8. 378(9799):1297-305. [Medline].
He M, van Dam RM, Rimm E, Hu FB, Qi L. Whole-grain, cereal fiber, bran, and germ intake and the risks of all-cause and cardiovascular disease-specific mortality among women with type 2 diabetes mellitus. Circulation. 2010 May 25. 121(20):2162-8. [Medline]. [Full Text].
Micha R, Wallace SK, Mozaffarian D. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: a systematic review and meta-analysis. Circulation. 2010 Jun 1. 121(21):2271-83. [Medline]. [Full Text].
Paynter NP, Mazer NA, Pradhan AD, Gaziano JM, Ridker PM, Cook NR. Cardiovascular risk prediction in diabetic men and women using hemoglobin A1c vs diabetes as a high-risk equivalent. Arch Intern Med. 2011 Oct 24. 171(19):1712-8. [Medline]. [Full Text].
Rexrode KM, Carey VJ, Hennekens CH, et al. Abdominal adiposity and coronary heart disease in women. JAMA. Dec 2 1998. 280(21):1843-8.
Bacha F, Edmundowicz D, Sutton-Tyrell K, Lee S, Tfayli H, Arslanian SA. Coronary artery calcification in obese youth: what are the phenotypic and metabolic determinants?. Diabetes Care. 2014 Sep. 37(9):2632-9. [Medline].
Das SR, Alexander KP, Chen AY, et al. Impact of body weight and extreme obesity on the presentation, treatment, and in-hospital outcomes of 50,149 patients with ST-Segment elevation myocardial infarction results from the NCDR (National Cardiovascular Data Registry). J Am Coll Cardiol. 2011 Dec 13. 58(25):2642-50. [Medline].
Thompson PD, Buchner D, Pina IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention). Circulation. Jun 24 2003. 107(24):3109-16.
Manson JE, Greenland P, LaCroix AZ, et al. Walking compared with vigorous exercise for the prevention of cardiovascular events in women. N Engl J Med. Sep 5 2002. 347(10):716-25.
Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2010 Dec 14. 56(25):2182-99. [Full Text].
Chiuve SE, Fung TT, Rexrode KM, et al. Adherence to a low-risk, healthy lifestyle and risk of sudden cardiac death among women. JAMA. 2011 Jul 6. 306(1):62-9. [Medline].
Stamatakis E, Hamer M, Dunstan DW. Screen-based entertainment time, all-cause mortality, and cardiovascular events: Population-based study with ongoing mortality and hospital events follow-up. J Am Coll Cardiol. 2011 Jan 18. 57(3):292-9. [Medline].
Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. Dec 4 2002. 288(21):2709-16.
Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005 Oct 25. 112(17):2735-52. [Medline].
Welsh JA, Sharma A, Cunningham SA, Vos MB. Consumption of added sugars and indicators of cardiovascular disease risk among US adolescents. Circulation. 2011 Jan 25. 123(3):249-57. [Medline].
Rugulies R. Depression as a predictor for coronary heart disease. a review and meta-analysis. Am J Prev Med. 2002 Jul. 23(1):51-61. [Medline].
Ghiadoni L, Donald AE, Cropley M, et al. Mental stress induces transient endothelial dysfunction in humans. Circulation. 2000 Nov 14. 102(20):2473-8. [Medline].
Hjemdahl P. Stress and the metabolic syndrome: an interesting but enigmatic association. Circulation. 2002 Nov 19. 106(21):2634-6. [Medline].
Shah AJ, Veledar E, Hong Y, Bremner JD, Vaccarino V. Depression and history of attempted suicide as risk factors for heart disease mortality in young individuals. Arch Gen Psychiatry. 2011 Nov. 68(11):1135-42. [Medline]. [Full Text].
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20. 359(21):2195-207. [Medline].
Chan DC, Pang J, Hooper AJ, et al. Elevated lipoprotein(a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia. Int J Cardiol. 2015 Dec 15. 201:633-8. [Medline].
Otvos JD, Jeyarajah EJ, Cromwell WC. Measurement issues related to lipoprotein heterogeneity. Am J Cardiol. 2002 Oct 17. 90(8A):22i-29i. [Medline].
Mendivil CO, Rimm EB, Furtado J, Chiuve SE, Sacks FM. Low-density lipoproteins containing apolipoprotein C-III and the risk of coronary heart disease. Circulation. 2011 Nov 8. 124(19):2065-72. [Medline].
Wilhelmsen L, Svardsudd K, Korsan-Bengtsen K, Larsson B, Welin L, Tibblin G. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J Med. 1984 Aug 23. 311(8):501-5. [Medline].
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23. 351(13):1296-305. [Medline].
Malkin CJ, Pugh PJ, Morris PD, Asif S, Jones TH, Channer KS. Low serum testosterone and increased mortality in men with coronary heart disease. Heart. 2010 Nov. 96(22):1821-5. [Medline].
Dong JY, Zhang YH, Qin LQ. Erectile dysfunction and risk of cardiovascular disease meta-analysis of prospective cohort studies. J Am Coll Cardiol. 2011 Sep 20. 58(13):1378-85. [Medline].
Ingelsson E, Lundholm C, Johansson AL, Altman D. Hysterectomy and risk of cardiovascular disease: a population-based cohort study. Eur Heart J. 2011 Mar. 32(6):745-50. [Medline].
Cappuccio FP, Cooper D, D'Elia L, Strazzullo P, Miller MA. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J. 2011 Jun. 32(12):1484-92. [Medline].
Laugsand LE, Vatten LJ, Platou C, Janszky I. Insomnia and the risk of acute myocardial infarction: a population study. Circulation. 2011 Nov 8. 124(19):2073-81. [Medline].
Oberg S, Cnattingius S, Sandin S, Lichtenstein P, Iliadou AN. Birth weight predicts risk of cardiovascular disease within dizygotic but not monozygotic twin pairs: a large population-based co-twin-control study. Circulation. 2011 Jun 21. 123(24):2792-8. [Medline].
Christoffersen M, Frikke-Schmidt R, Schnohr P, et al. Xanthelasmata, arcus corneae, and ischaemic vascular disease and death in general population: prospective cohort study. BMJ. 2011 Sep 15. 343:d5497. [Medline]. [Full Text].
Kestenbaum B, Katz R, de Boer I, et al. Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol. 2011 Sep 27. 58(14):1433-41. [Medline].
Bluemke DA, Achenbach S, Budoff M, et al. Noninvasive coronary artery imaging: magnetic resonance angiography and multidetector computed tomography angiography: a scientific statement from the american heart association committee on cardiovascular imaging and intervention of the council on cardiovascular radiology and intervention, and the councils on clinical cardiology and cardiovascular disease in the young. Circulation. 2008 Jul 29. 118(5):586-606. [Medline].
Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA. 2001 Sep 19. 286(11):1317-24. [Medline].
Polak JF, Pencina MJ, Pencina KM, et al. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med. 2011 Jul 21. 365(3):213-21. [Medline].
Costanzo P, Perrone-Filardi P, Vassallo E, et al. Does carotid intima-media thickness regression predict reduction of cardiovascular events? A meta-analysis of 41 randomized trials. J Am Coll Cardiol. 2010 Dec 7. 56(24):2006-20. [Medline].
Rosenberg S, Elashoff MR, Beineke P, et al. Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann Intern Med. 2010 Oct 5. 153(7):425-34. [Medline].
Wu CK, Lin JW, Caffrey JL, Chang MH, Hwang JJ, Lin YS. Cystatin C and long-term mortality among subjects with normal creatinine-based estimated glomerular filtration rates: NHANES III (Third National Health and Nutrition Examination Survey). J Am Coll Cardiol. 2010 Nov 30. 56(23):1930-6. [Medline].
Ridker PM, Genest J, Boekholdt SM, et al. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet. 2010 Jul 31. 376(9738):333-9. [Medline].
Stiles S. New CV risk-assessment guidance counts stroke with CHD risk. Medscape Medical News from WebMD. November 12, 2013. Available at http://www.medscape.com/viewarticle/814206. Accessed: November 26, 2013.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24. 129(25 Suppl 2):S49-73. [Medline].