Cardiovascular Risk Assessment with SCORE2 and SCORE2-OP

Definition and purpose

Cardiovascular risk assessment estimates an individual’s probability of experiencing cardiovascular disease (CVD) over a defined period. SCORE2 and SCORE2-Older Persons (SCORE2-OP) are European risk-prediction models designed to estimate 10-year risk of both fatal and non-fatal CVD events, specifically myocardial infarction and stroke.

They supersede risk models that estimate cardiovascular mortality alone because non-fatal events constitute an important component of the overall burden of atherosclerotic cardiovascular disease. SCORE2 is intended principally for adults aged 40–69 years, whereas SCORE2-OP is used in adults aged ≥70 years. SCORE2-OP accounts for the competing risk of death from non-cardiovascular causes, an important consideration in older populations.

Risk prediction is particularly relevant in adults with elevated blood pressure (BP), in whom absolute cardiovascular risk varies considerably according to age and the presence of concomitant risk factors. In contrast, patients with confirmed hypertension generally require BP-lowering treatment without additional risk stratification for that treatment decision.

Population to which SCORE2 and SCORE2-OP apply

SCORE2 and SCORE2-OP are intended for apparently healthy people or for individuals with elevated BP who do not already have a condition conferring sufficiently high cardiovascular risk.

They should not be applied as the principal risk tool in people with:

• Documented atherosclerotic cardiovascular disease (ASCVD)

• Diabetes mellitus in circumstances where diabetes-specific risk assessment or risk categorization is applicable

• Moderate or severe chronic kidney disease (CKD)

• Hypertension-mediated organ damage (HMOD)

• Probable or definite familial hypercholesterolaemia

• Other markedly abnormal single risk factors or genetic, rare lipid, or BP disorders

• Pregnancy

Established ASCVD includes previous acute coronary syndrome, chronic coronary syndromes, coronary revascularization, stroke, transient ischaemic attack, and peripheral arterial disease. Heart failure is also considered established clinical CVD in the risk-based approach to elevated BP.

Risk categories

In apparently healthy individuals, SCORE2 and SCORE2-OP estimates can be used to classify 10-year risk as follows:

The risk categories are distinct from the treatment threshold used in the BP guidelines. For adults with elevated BP, a calculated 10-year risk of ≥10% is considered sufficiently high to support BP-lowering treatment, whether through lifestyle intervention, pharmacological therapy, or both.

A person may also be considered at increased cardiovascular risk without a calculated SCORE2 or SCORE2-OP estimate when certain clinical conditions are present. These include diabetes mellitus, familial hypercholesterolaemia, established CVD, moderate or severe CKD, or HMOD.

Variables incorporated into SCORE2 and SCORE2-OP

The models include conventional cardiovascular risk factors:

• Age

• Sex

• Smoking status

• Systolic BP

• Cholesterol values

Risk estimation uses the appropriate sex-specific and smoking-specific table or calculator. The relevant BP and non-high-density lipoprotein cholesterol (non-HDL-C) values are then entered into the table or application. Estimates should be adjusted upwards as the individual approaches the next age category.

The models are calibrated to four European country-risk clusters according to national CVD mortality rates:

• Low risk

• Moderate risk

• High risk

• Very high risk

Correct selection of the country-risk cluster is therefore essential. The clusters include different European and surrounding countries, and the applicable regional category should be established before interpreting the calculated risk.

SCORE2 in adults aged 40–69 years

SCORE2 is recommended for adults aged 40–69 years with elevated BP who do not already have increased cardiovascular risk because of established CVD, moderate or severe CKD, HMOD, diabetes mellitus, or familial hypercholesterolaemia.

It estimates 10-year fatal and non-fatal CVD risk in people whose risk factors are untreated or have remained stable for several years. The estimate is intended to support decisions regarding prevention and, particularly, BP-lowering treatment in people with elevated BP.

SCORE2-OP in adults aged ≥70 years

SCORE2-OP is recommended for adults aged ≥70 years who have elevated BP but no established condition that already places them at increased risk.

Older adults require a specific model because the relationship between conventional risk factors and CVD risk changes with age, while the probability of non-cardiovascular mortality rises. A model that ignores competing mortality may overestimate the probability of a cardiovascular event and consequently overestimate the potential benefit of preventive treatment.

SCORE2-OP provides estimates for fatal and non-fatal CVD events and is adjusted for competing non-cardiovascular mortality. It can estimate both 5-year and 10-year risk.

SCORE2-Diabetes

Indication

SCORE2-Diabetes should be considered in patients aged ≥40 years with type 2 diabetes mellitus (T2DM) who do not have symptomatic ASCVD or severe target-organ damage (TOD). It is particularly relevant when assessing patients with T2DM and elevated BP who are younger than 60 years, because some such individuals have a 10-year CVD risk below 10%.

All patients with diabetes should first be evaluated for ASCVD and severe TOD. If either is present, risk estimation with SCORE2-Diabetes is not the basis for determining whether the individual is at increased risk.

Variables

SCORE2-Diabetes extends the SCORE2 methodology by incorporating diabetes-specific variables alongside conventional risk factors. These include:

• Age at diabetes diagnosis

• Glycated haemoglobin (HbA1c)

• Estimated glomerular filtration rate (eGFR)

• Age

• Smoking status

• Systolic BP

• Total cholesterol

• HDL cholesterol

The model estimates 10-year risk of fatal and non-fatal CVD events, including myocardial infarction and stroke, and is calibrated to the same four European CVD-risk country clusters used by SCORE2 and SCORE2-OP.

Severe target-organ damage

Severe TOD is defined by any of the following:

• eGFR <45 mL/min/1.73 m2, irrespective of albuminuria

• eGFR 45–59 mL/min/1.73 m2 with microalbuminuria, defined as a urinary albumin-to-creatinine ratio (UACR) of 30–300 mg/g

• Proteinuria, defined as UACR >300 mg/g

• Microvascular disease at three or more sites, such as microalbuminuria together with retinopathy and neuropathy

Risk thresholds generated by SCORE2-Diabetes should support, rather than replace, individualized decision-making. Other patient characteristics may justify treatment irrespective of the calculated threshold.

Assessment in people with elevated BP

Definition of the relevant BP group

The risk-based approach applies particularly to individuals with elevated office BP, defined in the source material as:

• Systolic BP 120–139 mmHg, or

• Diastolic BP 70–89 mmHg

For these individuals, cardiovascular risk is assessed by combining measured BP with the appropriate risk model and, where relevant, non-traditional risk modifiers.

Patients with confirmed hypertension are recommended to receive BP-lowering treatment, and further risk stratification is not required for allocating that treatment.

Conditions indicating increased risk without SCORE2 calculation

In a person with elevated BP, the following conditions independently indicate increased cardiovascular risk:

• Diabetes mellitus

• Familial hypercholesterolaemia

• Established CVD

• Moderate or severe CKD

• HMOD

Established CVD includes coronary disease, cerebrovascular disease, peripheral arterial disease, and heart failure.

Risk threshold for BP management

For adults with elevated BP and no independently high-risk condition, SCORE2 or SCORE2-OP should be used according to age. A 10-year predicted CVD risk of ≥10% identifies an individual as sufficiently high risk for BP-lowering treatment decisions, irrespective of age.

This threshold may lead to treatment with lifestyle measures, drug therapy, or both. The choice and intensity of treatment should be individualized.

Refining risk beyond SCORE2 and SCORE2-OP

Non-traditional risk modifiers

SCORE2 and SCORE2-OP include traditional risk factors but do not incorporate all non-traditional risk determinants. In individuals with borderline increased calculated risk, these additional factors may improve risk discrimination and may justify reclassification to a higher risk category.

Risk modifiers are particularly relevant when the calculated 10-year risk is ≥5% but <10% and the decision about initiating BP-lowering treatment is uncertain.

Additional investigations

After consideration of relevant risk modifiers, further investigations may be reasonable when treatment decisions remain unclear. The source material identifies the following options:

• Coronary artery calcium (CAC) score

• Carotid plaque assessment

• Femoral plaque assessment

• High-sensitivity cardiac troponin

• B-type natriuretic peptide

• Arterial stiffness measurement

CAC findings obtained incidentally from a previous chest CT may also be used to improve risk stratification and guide management of modifiable risk factors. CAC scoring may be considered when risk is close to a treatment decision threshold. Carotid ultrasound may be used as an alternative when CAC assessment is unavailable or impractical.

Carotid or femoral ultrasound should be considered only when the result is likely to alter management. Similarly, pulse-wave velocity measurement may be considered when assessment of arterial stiffness is likely to change treatment decisions.

Clinical evaluation required before risk calculation

Risk calculation is not a substitute for clinical assessment. The evaluation should establish:

• Age and sex

• Smoking status

• Systolic BP

• Total cholesterol and HDL cholesterol

• Presence of established CVD

• Diabetes status and, where relevant, diabetes duration

• Kidney function

• Albuminuria where diabetes-related target-organ damage is suspected

• Presence of HMOD

• Familial hypercholesterolaemia

• Other markedly elevated risk factors

The evaluation should also identify whether the individual belongs to a group for whom SCORE2 or SCORE2-OP is not intended.

Blood pressure measurement and confirmation

Although SCORE2-based risk assessment is performed using BP values, diagnosis of hypertension should be established separately.

When screening office BP is 140–159/90–99 mmHg, hypertension should preferably be confirmed using out-of-office measurement with ambulatory BP monitoring (ABPM) and/or home BP monitoring (HBPM). If these approaches are not feasible, repeated office measurements on more than one visit may be used.

When office BP is 160–179/100–109 mmHg, confirmation should occur promptly, preferably with home or ambulatory measurements. BP ≥180/110 mmHg requires exclusion of a hypertensive emergency.

At each office visit, three BP measurements should be recorded at intervals of 1–2 minutes. Additional readings are required if the first two differ by >10 mmHg, and the average of the final two readings is used.

Cardiovascular risk assessment in selected clinical settings

Diabetes

All patients with diabetes should be assessed for ASCVD and severe TOD. In T2DM without symptomatic ASCVD or severe TOD, SCORE2-Diabetes should be calculated from age 40 years onward.

For patients younger than 40 years, ASCVD risk factors should be assessed individually rather than relying on SCORE2-Diabetes.

Lifestyle management is an integral part of risk reduction. Smoking cessation is a primary target in patients with CVD and diabetes. Physical activity should be encouraged, with the principle that every increase in activity is valuable. In people with obesity and T2DM, weight reduction combined with increased daily physical activity and structured exercise is emphasized. A Mediterranean diet supplemented with olive oil and/or nuts reduces major cardiovascular events in patients with CVD.

Breast cancer and endocrine therapy

In breast cancer patients receiving endocrine therapy without pre-existing CVD, baseline cardiovascular risk assessment with SCORE2 or SCORE2-OP is recommended.

During endocrine therapy:

• Annual cardiovascular risk assessment is recommended in patients with high 10-year risk according to SCORE2 or SCORE2-OP.

• In patients with low or moderate 10-year risk, reassessment every five years should be considered.

Radiotherapy involving the heart

Baseline cardiovascular risk assessment and estimation of 10-year fatal and non-fatal CVD risk with SCORE2 or SCORE2-OP are recommended in the relevant setting. Baseline echocardiography should be considered in patients with previous CVD before radiotherapy involving a volume that includes the heart.

Opportunistic screening

Opportunistic screening of healthy individuals for cardiovascular risk factors and future cardiovascular risk using scoring systems such as SCORE2 and SCORE2-OP is recommended. The aim is to detect individuals at increased risk and guide treatment decisions.

Management implications of risk assessment

Lifestyle intervention

Lifestyle intervention forms the foundation of cardiovascular risk reduction. Recommendations include:

• Moderate-intensity aerobic exercise for at least 150 minutes per week, distributed as at least 30 minutes on 5–7 days per week; alternatively, 75 minutes of vigorous exercise per week over three days

• Complementary low- or moderate-intensity dynamic or isometric resistance training two to three times weekly

• Maintenance of a stable, healthy body mass index of 20–25 kg/m2

• Waist circumference below 94 cm in men and below 80 cm in women

• A healthy, balanced diet, such as a Mediterranean or DASH dietary pattern

• Alcohol consumption below approximately 100 g of pure alcohol per week; avoidance is preferred for optimal health outcomes

• Smoking cessation

Pharmacological BP lowering

The risk estimate helps determine whether pharmacological BP lowering should be added to lifestyle intervention in people with elevated BP. The principal first-line drug classes are:

• Angiotensin-converting enzyme (ACE) inhibitors

• Angiotensin receptor blockers (ARBs)

• Dihydropyridine calcium-channel blockers

• Thiazide or thiazide-like diuretics, including chlorthalidone and indapamide

These classes have demonstrated reductions in BP and CVD events and form the basis of recommended BP-lowering strategies.

Beta-blockers have demonstrated BP and cardiovascular event reduction but are not included among the principal first-line classes in the revised recommendation. They remain relevant when specifically indicated and may be added in resistant hypertension if not already required for another indication.

Treatment targets

For most adults receiving BP-lowering therapy, treated systolic BP should be targeted to 120–129 mmHg if tolerated. If systolic BP is at or below this target but diastolic BP remains ≥80 mmHg, intensification to achieve diastolic BP of 70–79 mmHg may be considered.

More lenient targets may be appropriate in patients with:

• Symptomatic orthostatic hypotension before treatment

• Age ≥85 years

• Clinically significant moderate or severe frailty

• Limited predicted lifespan, defined in the source material as <3 years

In these settings, a target such as systolic BP <140 mmHg or BP <140/90 mmHg may be considered according to the clinical circumstances.

Resistant hypertension

When BP remains uncontrolled despite a three-drug combination, addition of spironolactone should be considered. If spironolactone is ineffective or not tolerated, alternatives include:

• Eplerenone

• A beta-blocker, if not already indicated

• A centrally acting BP-lowering drug

• An alpha-blocker

• Hydralazine

• A potassium-sparing diuretic

Catheter-based renal denervation may be considered in selected patients at medium- to high-volume centres. Candidates may include those with resistant hypertension uncontrolled despite three BP-lowering drugs, including a thiazide or thiazide-like diuretic, who prefer the procedure after shared risk–benefit discussion and multidisciplinary assessment. It may also be considered in patients with increased CVD risk and uncontrolled hypertension despite fewer than three drugs under similar conditions.

Renal denervation is not recommended as first-line treatment. It is also not recommended in patients with eGFR <40 mL/min/1.73 m2 or secondary hypertension until further evidence is available.

Guideline recommendations

Key recommendations are summarized below.

Communication and shared decision-making

Risk estimates should be used to support a discussion about treatment intensity and additional preventive measures rather than treated as an automatic prescription. This is particularly important when the calculated risk is close to a treatment threshold, when risk modifiers are present, or when comorbidity, frailty, life expectancy, or treatment tolerability may alter the balance of benefit and harm.

In patients with T2DM, SCORE2-Diabetes thresholds are guidance tools. Individual characteristics may support treatment even when the calculated risk is below a suggested threshold, or may lead to a decision not to intensify therapy despite a numerical estimate.

Prognosis and follow-up

SCORE2 and SCORE2-OP provide estimates of 10-year risk rather than a definitive individual prognosis. Their clinical value lies in improving risk classification and informing preventive treatment.

Follow-up frequency depends on the clinical setting and baseline risk:

• During endocrine therapy for breast cancer, annual reassessment is recommended for patients with high 10-year risk.

• In breast cancer patients with low or moderate risk, assessment every five years should be considered.

• In other patients, reassessment should reflect changes in BP, smoking status, lipid values, diabetes, kidney function, HMOD, and other clinical conditions.

Risk should be recalculated when important risk factors change or when a new condition arises that changes the person’s risk category. The source material does not specify a universal reassessment interval for the general population or for all patients with elevated BP.