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Estimation of cardiovascular risk in an individual patient without known cardiovascular disease
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Estimation of cardiovascular risk in an individual patient without known cardiovascular disease
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2016. | This topic last updated: Mar 29, 2016.

INTRODUCTION — Atherosclerotic cardiovascular disease (CVD) is common in the general population, affecting the majority of adults past the age of 60 years. As a diagnostic category, CVD includes four major areas:

Coronary heart disease (CHD) manifested by fatal or nonfatal myocardial infarction (MI), angina pectoris, and/or heart failure (HF)

Cerebrovascular disease manifested by fatal or nonfatal stroke and transient ischemic attack

Peripheral artery disease manifested by intermittent claudication and critical limb ischemia

Aortic atherosclerosis and thoracic or abdominal aortic aneurysm

Although CHD is the most common manifestation of CVD, CHD represents only approximately 50 percent of the total number of first CVD events. The lifetime risk of CHD was illustrated in a study of 7733 participants, age 40 to 94, in the Framingham Heart Study who were initially free of CHD [1]. The lifetime risk for individuals at age 40 was 49 percent in men and 32 percent in women. Even those who were apparently free from disease at age 70 had a lifetime risk of 35 percent and 24 percent in men and women, respectively. The lifetime risk of CHD varies importantly with the aggregate risk factor burden (figure 1) [2]. (See 'Lifetime risk' below.)

Many risk factors for cardiovascular disease are modifiable by specific preventive measures. In the worldwide INTERHEART study of patients from 52 countries, nine potentially modifiable factors accounted for over 90 percent of the population-attributable risk of a first MI [3]. These included smoking, dyslipidemia, hypertension, diabetes, abdominal obesity, psychosocial factors (eg, depression, perceived stress, life events), daily consumption of fruits and vegetables, regular alcohol consumption, and regular physical activity. An overview of the multiple cardiovascular disease risk factors is presented separately. (See "Overview of the risk equivalents and established risk factors for cardiovascular disease".)

While a general estimate of the relative risk for CVD can be approximated by counting the number of traditional risk factors present in a patient, a more precise estimation of the absolute risk for a first CVD event is desirable when making treatment recommendations for a specific individual. The predictive value of risk factors and the use of multivariate risk models to estimate cardiovascular risk in an individual patient will be reviewed here. The use of the risk models in decision making for the management of hypercholesterolemia or initiation of aspirin therapy for primary prevention is discussed elsewhere. (See "Overview of primary prevention of coronary heart disease and stroke" and "Treatment of lipids (including hypercholesterolemia) in primary prevention", section on 'Deciding whom to treat' and "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease".)

WHO SHOULD UNDERGO ESTIMATION OF CARDIOVASCULAR DISEASE RISK? — Certain individuals with established cardiovascular disease (CVD) or CVD risk equivalents are known to be at high risk of recurrent cardiovascular events and should be treated with appropriate secondary prevention measures. (See "Prevention of cardiovascular disease events in those with established disease or at high risk".)

Patients aged 20 years or older without established CVD should undergo periodic cardiovascular risk assessment every three to five years [4-6]. Periodic risk assessment offers the opportunity to identify CVD risk factors and offer guidance on the appropriate management of specific risk factors (eg, dietary modifications for hypertension or dyslipidemia, etc) and overall CVD risk (eg, maintaining a healthy diet, regular exercise, etc). It is unknown at what age periodic risk assessment should no longer be performed, but many of the validated risk models have only included patients up to 79 years of age or less. Decisions regarding the discontinuation of periodic risk assessment should be made in collaboration with each individual patient based on the patient’s overall functional status, life expectancy, and values and preferences for risk factor modification.

MULTIVARIATE RISK MODELS — A number of multivariate risk models have been developed for estimating the risk of initial cardiovascular events in apparently healthy, asymptomatic individuals based upon assessment of multiple variables. While all of the risk models have advantages and disadvantages, no single risk model will be appropriate for all patients [7,8]. The choice a specific risk model for cardiovascular disease (CVD) risk assessment should be individualized based on patient-specific characteristics (eg, age, gender, ethnicity). Most experts feel that the use of risk models that predict hard CVD events (ie, death, myocardial infarction [MI], stroke) are preferred over those which include other endpoints (ie, revascularization).

Framingham risk score (1998) — The original Framingham risk score (1998), published in 1998, was derived from a largely Caucasian population of European descent [9]. Subsequent studies have suggested that the Framingham risk score performs well for prediction of CHD events in black and white women and men [10].

Prediction variables used in Framingham CHD risk score (1998)

Age

Gender

Total or LDL cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Diabetes mellitus (yes or no)

Current smoking (yes or no)

Prediction variables not used in the Framingham CHD risk score (1998)

Blood pressure treatment (yes or no)

Family history of CVD (yes or no)

Endpoints assessed in Framingham CHD risk score (1998)

CHD death

Nonfatal MI

Unstable angina

Stable angina

ATP III hard CHD risk score (2002) — The Framingham risk score was modified (2002) by the third Adult Treatment Panel (ATP III) for use in their recommendations for screening for and treatment of dyslipidemia (table 1A-B) [11]. The modifications include elimination of diabetes from the algorithm, since it was considered to be a CHD equivalent; broadening of the age range; and inclusion of hypertension treatment and age-specific points for smoking and total cholesterol.

Prediction variables used in ATP III hard CHD risk score (2002)

Age

Gender

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Blood pressure treatment (yes or no)

Current smoking (yes or no)

Prediction variables not used in the ATP III hard CHD risk score (2002)

Diabetes mellitus (yes or no)

Family history of CVD (yes or no)

Endpoints assessed in ATP III hard CHD risk score (revised 2002)

CHD death

Nonfatal MI

Framingham General CVD risk score (2008) — The original 1998 and revised 2002 Framingham risk scores do not include all of the potential manifestations and adverse consequences of atherosclerosis, such as stroke, transient ischemic attack, claudication and heart failure (HF) (although manifestations of aortic atherosclerosis were omitted). These patient-important vascular outcomes were included in the development of the 2008 Framingham general cardiovascular risk score, which was shown to have reliable predictive ability (calculator 1 and calculator 2) [12]. The estimated risk of developing a cardiovascular event will be higher with this risk score than with those that predict only CHD events.

Prediction variables used in Framingham General CVD risk score (2008)

Age

Gender

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Blood pressure treatment (yes or no)

Diabetes mellitus (yes or no)

Current smoking (yes or no)

Prediction variables not used in the Framingham General CVD risk score (2008)

Family history of CVD (yes or no)

Endpoints assessed in Framingham General CVD risk score (2008)

CHD death

Nonfatal MI

Coronary insufficiency or angina

Fatal or nonfatal ischemic or hemorrhagic stroke

Transient ischemic attack

Intermittent claudication

HF

SCORE CVD death risk score (2003) — SCORE, which is recommended in the 2007 European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice, included data on more than 200,000 patients pooled from cohort studies in 12 European countries [4,13]. A unique aspect of SCORE is that separate risk scores were calculated for high- and low-risk regions of Europe. The predictive value of SCORE was high in each component study cohort.

SCORE differs from the earlier Framingham risk models (and others) in two important ways: it estimates the 10-year risk of any first fatal atherosclerotic event (eg, stroke or ruptured abdominal aneurysm), not just CHD-related deaths, and it estimates cardiovascular disease mortality.

Prediction variables used in SCORE CVD death risk estimator (2003)

Age

Gender

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Current smoking (yes or no)

Region of Europe (high risk or low risk region)

Prediction variables not used in the SCORE CVD death risk estimator (2003)

Blood pressure treatment (yes or no)

Diabetes mellitus (yes or no)

Family history of CVD (yes or no)

Endpoints assessed in SCORE CVD death risk estimator (2003)

Cardiovascular disease death (including CHD, arrhythmia, HF, stroke, aortic aneurysm, and peripheral vascular disease)

QRISK and QRISK2 — The QRISK and the updated QRISK2 algorithms were developed to predict cardiovascular risk in patients from different ethnic groups living in England and Wales [14,15]. The QRISK2 algorithm included risk predictors used in the modified Framingham/ATP III model, as well as ethnicity, socioeconomic status, family history, and other medical variables such as diabetes, chronic renal disease, atrial fibrillation, and rheumatoid arthritis. QRISK2 more accurately identified those at risk than the modified Framingham/ATP III model in this population.

Prediction variables used in QRISK CVD risk estimator (2007)

Age

Gender

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Blood pressure treatment (yes or no)

Current smoking (yes or no)

Family history of CVD in first degree relative aged <60 years (yes or no)

Region of United Kingdom (score based on levels of unemployment, overcrowding, car ownership, home ownership)

Body mass index (kg/m2)

Prediction variables not used in the QRISK CVD risk estimator (2007)

Diabetes mellitus (yes or no)

Endpoints assessed in QRISK CVD risk estimator (2007)

CHD death

Nonfatal MI

Coronary insufficiency or angina

Coronary revascularization

Fatal or nonfatal stroke

Transient ischemic attack

Intermittent claudication

Reynolds CVD risk score for women (2007) — The Reynolds risk score for women was developed from a prospective cohort of nearly 25,000 American women without diabetes [16]. The primary differences between the Reynold risk score and most other risk estimations are the inclusion of family history of MI and high-sensitivity C-reactive protein (hs-CRP) as variables in the risk calculator. (See "C-reactive protein in cardiovascular disease".)

Prediction variables used in Reynolds CVD risk score for women (2007)

Age

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Diabetes mellitus assessed by hemoglobin A1c (percent)

Current smoking (yes or no)

Parental history of MI before age 60 years (yes or no)

Serum hs-CRP (mg/L)

Prediction variables not used in the Reynolds CVD risk score for women (2007)

Blood pressure treatment (yes or no)

Endpoints assessed in Reynolds CVD risk score for women (2007)

Cardiovascular death

Nonfatal MI

Nonfatal stroke

Coronary revascularization

Reynolds CVD risk score for men (2008) — Similarly to the Reynolds risk score for women, the Reynolds risk score for men was developed from a prospective cohort of over 10,000 American men without diabetes and also included family history of MI and hs-CRP as variables in the risk calculator [17]. Unlike the Reynolds risk score for women, hemoglobin A1c level was not included as a variable in the Reynolds risk score for men. (See "C-reactive protein in cardiovascular disease".)

Prediction variables used in Reynolds CVD risk score for men (2008)

Age

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Current smoking (yes or no)

Parental history of MI before age 60 years (yes or no)

Serum hs-CRP (mg/L)

Prediction variables not used in the Reynolds CVD risk score for men (2008)

Diabetes mellitus (yes or no)

Blood pressure treatment (yes or no)

Endpoints assessed in Reynolds CVD risk score for men (2008)

Cardiovascular death

Nonfatal MI

Nonfatal stroke

Coronary revascularization

ACC/AHA pooled cohort hard CVD risk calculator (2013) — Several cohorts of patients were used to develop the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular risk calculator (calculator 3), the first risk model to include data from large populations of both Caucasian and African-American patients [5]. The model includes the same parameters as the 2008 Framingham General CVD model, but in contrast to the 2008 Framingham model includes only hard endpoints (fatal and nonfatal MI and stroke). However, while the calculator appears to be well-calibrated in some populations similar to those for which the calculator was developed (REGARDS), it has not been as accurate in other populations (Rotterdam) [6,18-20].

Prediction variables used in ACC/AHA pooled cohort hard CVD risk calculator (2013)

Age

Gender

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Blood pressure treatment (yes or no)

Diabetes mellitus (yes or no)

Current smoking (yes or no)

Prediction variables not used in the ACC/AHA pooled cohort hard CVD risk calculator (2013)

Family history of CVD (yes or no)

Endpoints assessed in ACC/AHA pooled cohort hard CVD risk calculator (2013)

CHD death

Nonfatal MI

Fatal stroke

Nonfatal stroke

JBS3 risk score (2014) — The Joint British Societies (JBS) released a new risk calculator in 2014 which is based on the QRISK Lifetime cardiovascular risk calculator and incorporates many of the same variables from the original QRISK and QRISK2 scores [21]. However, the JBS3 risk calculator extends the assessment of risk beyond the 10-year window of most prior risk estimators and allows for the estimate of "heart age" and the assessment of risk over longer intervals (eg, 50 years for a 45-year-old patient, 30 years for a 65-year-old patient, etc). The JBS calculator also allows for the estimated impact of lifestyle modifications on future risk (ie, the impact of smoking cessation on CVD risk), but these data are from statistical models and have not been externally validated. A link to this calculator can be found at the JBS3 risk website.

Prediction variables used in JBS3 risk estimator (2014)

Age

Gender

Ethnicity

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Systolic blood pressure (mmHg)

Blood pressure treatment (yes or no)

Diabetes mellitus (yes or no)

Current smoking (yes or no)

Family history of CVD in first degree relative aged <60 years (yes or no)

Chronic kidney disease

Atrial fibrillation

Rheumatoid arthritis

Region of United Kingdom (score based on levels of unemployment, overcrowding, car ownership, home ownership)

Body mass index (kg/m2)

Prediction variables not used in the JBS3 risk estimator (2014)

None

Endpoints assessed in JBS3 risk estimator (2014)

CHD death

Nonfatal MI

Coronary insufficiency or angina

Coronary revascularization

Fatal or nonfatal stroke

Transient ischemic attack

Intermittent claudication

MESA risk score (2015) — The Multi-Ethnic Study of Atherosclerosis (MESA) published a risk score in 2015 which was validated in two separate prospective cohort groups [22]. While many of the traditional risk factors are also part of the MESA risk score, this risk estimator also includes multiple ethnic backgrounds (calculator 4). The MESA risk score also incorporates coronary artery calcium score to further classify the patients, although an estimate of risk can also be made without entering the CAC score for patients.

Prediction variables used in MESA risk score (2015)

Age

Gender

Ethnicity (non-Hispanic white, Chinese American, African American, Hispanic)

Total cholesterol (mg/dL)

HDL cholesterol (mg/dL)

Lipid lowering treatment (yes or no)

Systolic blood pressure (mmHg)

Blood pressure treatment (yes or no)

Diabetes mellitus (yes or no)

Current smoking (yes or no)

Family history of myocardial infarction at any age (yes or no)

Coronary artery calcium score

Prediction variables not used in the MESA risk score (2015)

Family history of CVD other than myocardial infarction

Endpoints assessed in MESA risk score (2015)

CHD death

Nonfatal MI

Resuscitated cardiac arrest

Coronary revascularization in patient with angina

Comparison among different risk scores — An important component of multivariate risk models for the estimation of CVD risk is that many of the risk factors (eg, age, hypertension, serum LDL-cholesterol) are recognized as producing a graded increase in risk (figure 2) [23]. In addition, these models estimate risk of an individual patient over the next 10 years, even though the risk models have been derived from large population-based studies.

Several studies have suggested that the Framingham criteria either overestimate or underestimate the risk of initial coronary heart disease (CHD) events in other populations such as Japanese American and Hispanic men, Native American women, European and Asian populations, and African-American men and women, as well as patients older than age 85 years [4,7,8,10,13,24-30]. These differences are partly explained by the research methods used, adjudication procedures, time intervals studied, and calendar year of the baseline evaluations. Multiple models, including SCORE and QRISK2, have been developed in an attempt to provide better predictive accuracy for European patients [4,13-15,27-29].

How a risk score performs is largely dependent on population characteristics along with the presence or absence of primary preventive therapies to address relevant risk factors. In an attempt to assess the performance of risk scores in a diverse population, five risk scores (1998 Framingham, 2002 ATP III, 2008 Framingham, Reynolds Risk Score, and 2013 AHA/ACC score) were calculated for 4227 racially diverse participants of the MESA cohort (42 percent white, 26 percent African American, 20 percent Hispanic, 12 percent Chinese) ages 50 to 74 years and without CVD or diabetes at baseline (follow-up 10.2 years) [7]. When comparing the predicted and observed rates of CVD, four of the five risk scores significantly overestimated the 10-year CVD risk (between 25 and 115 percent), with only the Reynolds Risk score slightly underestimating risk (3 percent underestimation). In a separate study comparing the 2013 AHA/ACC calculator with the ATP III risk estimator among 2435 participants in the Framingham offspring and third-generation cohorts who were followed for over nine years, the 2013 AHA/ACC calculator identified significantly more patients as statin eligible and more accurately identified patients who were at risk for incident CVD [31].

A variety of issues may underlie these differences, including secular changes in risk factors, greater use of cardiovascular prevention medicines and strategies over the past two decades, and a general decline in CVD morbidity and mortality in more recent times. The exact reasons for overestimation of risk are not known. In addition to these findings reinforcing the importance of being familiar with multiple risk scores and choosing the most applicable risk score for each individual patient (based upon the patient's unique characteristics), the potential for overestimation of CVD risk should be recognized in the discussion of risk and the decision-making process regarding therapies aimed at primary prevention.

Limitations of current vascular disease prediction models — The following represent important limitations to current risk models:

Risk assessments that stratify patients according to the number of defined risk factors can identify high-risk persons, but they tend to falsely reassure persons deemed to be at low risk who may have multiple marginal abnormalities (figure 1) [2,32]. (See "Overview of the risk equivalents and established risk factors for cardiovascular disease", section on 'Prevalence of cardiovascular disease risk factors'.)

Risk models identify patients who are more or less likely to develop cardiovascular disease within a defined period (eg, 10 years for CHD in the Framingham model). This approach does not consider lifetime risk, which might be substantially higher and amenable to aggressive risk factor reduction [2,33-35]. However, the 2013 ACC/AHA guideline on the assessment of cardiovascular risk calculator does offer an estimate of lifetime risk [5]. (See 'Lifetime risk' below.)

Some risk scores have been found to overestimate 10-year risk of CVD. (See 'Comparison among different risk scores' above.)

There is significant variability in predicted risk when multiple risk scores are applied to the same population, particularly when used in a population that is different from the validation cohort of the risk score [7,8].

The severity and frequency of the first vascular disease event has decreased over the last 40 years [36].

The relative effects of traditional risk factors differ according to the vascular disease outcome being evaluated [36].

Some risk models do not include patient important CVD outcomes such as stroke, HF, or development of symptomatic peripheral artery disease.

Lifetime risk — The lifetime risk of developing CVD has been assessed in a variety of cohorts as well as a meta-analysis of 18 cohorts involving over 257,000 men and women [2,37]. Data from the Framingham Heart Study were used to assess long-term outcomes according to risk status in individuals at age 50 without known cardiovascular disease, and the authors of the meta-analysis assessed long-term outcomes for participants at ages 45, 55, 65, and 75 years [2,37]. Risk factors within the participants were defined as follows:

Optimal risk factors:

Total cholesterol <180 mg/dL (4.7 mmol/L)

Untreated blood pressure <120/<80 mmHg

Nonsmoker

No diabetes

Not optimal risk factors (among nonsmokers without diabetes):

Total cholesterol 180 to 199 mg/dL (4.8 to 5.1 mmol/L)

Untreated systolic blood pressure 120 to 139 mmHg or diastolic blood pressure 80 to 89 mmHg

Elevated risk factors (among nonsmokers without diabetes):

Total cholesterol 200 to 239 mg/dL (5.2 to 6.1 mmol/L)

Untreated systolic blood pressure 140 to 159 mmHg or diastolic blood pressure 90 to 99 mmHg

Major risk factors:

Treated hyperlipidemia or total cholesterol ≥240 mg/dL (6.2 mmol/L)

Treated hypertension or untreated systolic pressure ≥160 mmHg or diastolic pressure ≥100 mmHg

Current smoking

Diabetes

The following findings were noted in the Framingham study (figure 1) and confirmed in the meta-analysis:

The lifetime risk of CVD increased progressively with the number and intensity of risk factors.

Participants with optimal risk factors had, when compared with those with ≥2 major risk factors, markedly lower lifetime risks of CVD at all age levels. As an example, among persons 45 years of age, those with all optimal risk factors had a lifetime risk of developing CVD of 4.1 percent compared with a 30.7 percent lifetime risk for those with two or more major risk factors.

Although the difference was less pronounced, the lifetime cardiovascular risk was significantly lower in participants with optimal risk factors compared with those with ≥1 not optimal risk factor. As an example, among persons 65 years of age, those with all optimal risk factors had a lifetime risk of developing CVD of 12.4 percent compared with a 25 percent lifetime risk for those with one or more not optimal risk factors.

Many individuals with a low 10-year risk, as calculated using the above models, will still have a high lifetime risk as the strongest determinant of risk in most risk calculators is age. This was modeled in a study of nearly 4000 individuals less than 50 years of age in the MESA and CARDIA studies in whom the burden of atherosclerosis was evaluated [38]. Ten-year and lifetime risks were assigned to each individual and patients were then divided into three groups:

Low 10-year (<10 percent) and low-lifetime (<39 percent) risk

Low 10-year (<10 percent) and high-lifetime (≥39 percent) risk

High 10-year (≥10 percent) risk or diabetes mellitus

The groups were then compared with regard to both their baseline levels of subclinical atherosclerosis (carotid intima-media thickness or coronary artery calcium [CAC] score) and its progression. The group with a low 10-year and high-lifetime risk had both a significantly greater burden of baseline subclinical atherosclerosis as well as a significantly higher rate of CAC progression than the group with a low 10-year and low-lifetime risk. As expected, outcomes in these two groups were significantly better than those in the high 10-year risk group.

ADDITIONAL RISK ASSESSMENT — The use of evaluations beyond traditional risk factor assessment was considered in the ACC/AHA Risk Assessment report [5]. The opinion of this expert committee was that quantitative risk assessment should occur first, and if a risk-based treatment decision is uncertain, assessment of family history of CVD, hs-CRP, coronary artery calcium score, or ankle-brachial index may be considered to inform treatment decision making. The committee did not recommend routine measurement of carotid intima-media thickness for risk assessment a first atherosclerotic CVD event. The committee also did not recommend use of ApoB, chronic kidney disease, albuminuria, or cardiorespiratory fitness evaluation for risk assessment for a first atherosclerotic CVD event.

In a 2016 study that assessed the impact of 13 negative risk markers (including coronary artery calcium of 0, normal carotid intima media thickness, C-reactive protein <2 mg/L, B-type natriuretic peptide <100 pg/mL, and negative family history, among others) on the future risk of all CVD and CHD in 6814 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without known CVD at baseline, a coronary artery calcium score of 0 was the strongest modulator of future risk and had the greatest impact on net reclassification of risk [39]. Future studies that incorporate additional risk factors into the traditional risk models may further guide clinicians in the assessment of individual CVD risk. (See "Diagnostic and prognostic implications of coronary artery calcification detected by computed tomography", section on 'CAC and prognosis in asymptomatic patients'.)

The discussion of this additional tools for risk assessment is provided separately. (See "Overview of the risk equivalents and established risk factors for cardiovascular disease", section on 'Family history' and "Screening for cardiovascular risk with C-reactive protein" and "Diagnostic and prognostic implications of coronary artery calcification detected by computed tomography" and "Noninvasive diagnosis of arterial disease", section on 'Ankle-brachial index' and "Carotid intima-media thickness".)

SUMMARY AND RECOMMENDATIONS

A number of multivariate risk models have been developed for estimating the risk of cardiovascular events in apparently healthy, asymptomatic individuals based upon assessment of multiple variables. While all of the risk models have advantages and disadvantages, no single risk model will be appropriate for all patients. The choice of a specific risk model for cardiovascular disease (CVD) risk assessment should be individualized based on patient-specific characteristics (eg, age, gender, ethnicity). However, our experts feel that the use of risk models which predict hard events (ie, death, myocardial infarction [MI], stroke) are preferred over those which include other endpoints (ie, revascularization). (See 'Multivariate risk models' above.)

Patients aged 20 years or older without established CVD should undergo periodic cardiovascular risk assessment every three to five years. Periodic risk assessment offers the opportunity to identify CVD risk factors and offer guidance on the appropriate management of specific risk factors (eg, dietary modifications for hypertension or dyslipidemia, etc) and overall CVD risk (eg, maintaining a healthy diet, regular exercise, etc). It is unknown at what age periodic risk assessment should no longer be performed. (See 'Who should undergo estimation of cardiovascular disease risk?' above.)

The use of the risk models in decision making for the management of hypercholesterolemia or initiation of aspirin therapy for primary prevention is discussed elsewhere. (See "Treatment of lipids (including hypercholesterolemia) in primary prevention", section on 'Deciding whom to treat' and "Benefits and risks of aspirin in secondary and primary prevention of cardiovascular disease".)

Certain individuals with established CVD or CVD risk equivalents are known to be at high risk of recurrent cardiovascular events and should be treated with appropriate secondary prevention measures. (See "Prevention of cardiovascular disease events in those with established disease or at high risk".)

All of the risk models are subject to limitations, the most important of which is the CVD risk prediction over a defined period of time (usually 10 years) which may poorly characterize a person's long-term CVD risk, particularly in younger patients. Many individuals with a low 10-year risk, as calculated using the above models, will still have a high lifetime risk as the largest driver of risk in most risk calculators is age. (See 'Limitations of current vascular disease prediction models' above and 'Lifetime risk' above.)

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