Clinical Quick Reference — Prevention of CVD in Clinical Practice
Published: European Heart Journal (2021) 42, 3227–3337 Developed by: ESC Task Force for CVD Prevention Endorsed by: EAPC, EAS, EHN, ESH, EURO-ASPIRE, and 7+ medical societies DOI:10.1093/eurheartj/ehab484
The 2021 ESC guidelines on cardiovascular disease prevention introduce significant updates emphasizing risk stratification using SCORE2, intensive stepwise treatment approaches, and integration of lifestyle and psychosocial factors into CVD prevention strategies. These recommendations reflect current evidence and aim to reduce CVD burden through personalized, patient-centered care.
Major New Class I Recommendations
SCORE2 Risk Assessment: 10-year fatal and nonfatal CVD risk estimation for apparently healthy people <70 years using age, sex, systolic BP, non-HDL-C, smoking status
SCORE2-OP (≥70 years): Age-adjusted risk algorithm for elderly population
Mediterranean Diet Adoption: To lower CVD risk with emphasis on olive oil, fruits, vegetables, whole grains, legumes, nuts
Alcohol Limitation: Maximum 100g per week (14 units/week)
Smoking Cessation: Recommended for all smokers regardless of weight gain considerations
Intensive Lipid-Lowering (Secondary Prevention): Ultimate LDL-C <1.4 mmol/L (55 mg/dL) with ≥50% reduction using statin + ezetimibe ± PCSK9i
Blood Pressure Targets: <140/90 mmHg for all; SBP 120–130 mmHg ages 18–69; SBP <140 and down to 130 if tolerated ages ≥70; DBP <80 mmHg
Type 2 DM with ASCVD/CKD: GLP-1RA or SGLT2i recommended for CV/renal benefit
Fish Consumption: Weekly intake, preferably fatty fish; restrict processed meat
Mental Health Screening: Mental disorders with significant functional impairment considered influencing CVD risk
Cardiac Rehabilitation: Structured, multidisciplinary EBCR program after ASCVD events/revascularization
Updated Class IIa Recommendations (Should be Considered)
Sedentary time reduction and light activity throughout the day
Wearable activity trackers for increased physical activity participation
Bariatric surgery for obesity when lifestyle intervention fails in high-risk individuals
Psychotherapeutic stress management referral for ASCVD patients
Antidepressive (SSRI) therapy for depression in CHD patients
LDL-C <1.4 mmol/L (55 mg/dL) with ≥50% reduction for very high-risk apparently healthy <70yo
LDL-C <1.8 mmol/L (70 mg/dL) with ≥50% reduction for high-risk apparently healthy ≥70yo
Cardiovascular Risk Assessment
SCORE2 and SCORE2-OP Risk Estimation
SCORE2 (Age <70): Estimates 10-year fatal and nonfatal CVD events (myocardial infarction, stroke) using age, sex, systolic BP, non-HDL-C, and smoking status. Calibrated to four risk clusters of European countries (low, moderate, high, very high mortality).
SCORE2-OP (Age ≥70): Modified algorithm adjusting for age-related CV risk relationships and competing non-CV mortality. Distinguishes lifetime benefit strategies in older populations.
CVD Risk Categories and Treatment Targets
Risk Category
SCORE2 Risk Threshold
LDL-C Goal
SBP Goal
Primary Strategy
Low-to-Moderate
<5% (age 50-69)
<3.0 mmol/L (116 mg/dL)
<130 mmHg
Lifestyle; statin if indicated
High
5-10% (age 50-69)
<1.8 mmol/L (70 mg/dL)
<130 mmHg
Statin ± ezetimibe
Very High
≥10% (age 50-69)
<1.4 mmol/L (55 mg/dL), ≥50% reduction
<130 mmHg
Intensive: statin + ezetimibe ± PCSK9i
Established ASCVD
Very High (residual risk)
<1.4 mmol/L (55 mg/dL), ≥50% reduction
<130 mmHg if tolerated
Intensive lipid & BP lowering
Lifetime CVD Risk and Risk Modifiers
Lifetime risk assessments communicate long-term prevention benefits to patients and guide treatment intensification in younger individuals. Consider these risk modifiers:
Psychosocial factors (depression, stress, social isolation)
Ethnicity and genetic/familial factors (family history of premature CVD)
Women <50 years and men <40 years have low 10-year CVD risk but may harbor high lifetime risk or unfavorable modifiable risk factors. Sex-specific considerations include:
Pregnancy complications (preeclampsia, gestational diabetes, stillbirth) as CVD risk markers
Migraine with aura associated with stroke risk; avoid combined hormonal contraceptives
Erectile dysfunction as CVD risk indicator in men
Hormonal therapy risk/benefit assessment
Type 2 Diabetes Mellitus
Most type 2 DM patients (especially with age >40 years or duration >10 years) are at high or very high CV risk. Intensive BP, lipid, and glucose control with cardioprotective agents (GLP-1RA, SGLT2i) are essential. Type 2 DM without overt ASCVD may be at very high risk if accompanied by severe TOD or multiple CV risk factors.
Chronic Kidney Disease (CKD)
CKD without diabetes or ASCVD: eGFR 30–44 mL/min/1.73m² or ACR ≥30 mg/mmol = high risk. Severe CKD (eGFR <30) or ACR >300 = very high risk. CKD with established ASCVD or DM = very high risk.
Familial Hypercholesterolaemia (FH)
Genetic LDL-C elevation (heterozygous FH ~0.25% population; homozygous ~0.02%) = high or very high risk depending on mutation type, LDL-C level, presence of ASCVD. Intensive lipid-lowering therapy with PCSK9i and/or combination agents required.
Atorvastatin 40–80 mg or rosuvastatin 20–40 mg daily. Expected LDL-C reduction 45–55%. Assess response at 4–12 weeks. For statin intolerance, consider alternative or reduced dose.
Angiotensin II Receptor Blockers (ARB): Losartan, valsartan, olmesartan. Equivalent to ACEi; alternative for cough intolerance. SE: hyperkalemia, angioedema (rare), hypotension.
Beta-Blockers: Indicated for post-MI, HF with reduced EF, atrial fibrillation, thyrotoxicosis. SE: fatigue, sexual dysfunction, asthma/COPD exacerbation.
Combination strategies: Most patients require 2–3 agents. Dual and triple fixed-dose combinations improve adherence. Start with low-dose combination therapy in moderate-to-severe hypertension.
Screening & Measurement
Office BP: Standardized technique: seated position, feet on ground, arm at heart level, 5 minutes rest. Three readings at 1–2 minute intervals on ≥2 visits. Average for diagnosis.
Home BP Monitoring (HBPM): Patient-measured BP at home; values typically 5 mmHg lower than office. Detects white-coat and masked hypertension; monitors treatment response.
24-Hour Ambulatory BP Monitoring (ABPM): Gold standard for diagnosis. Identifies white-coat hypertension, masked hypertension, blunted nocturnal dipping. Prognostically valuable; night-time dipping associated with better outcomes.
Class IRecommendation: 150–300 minutes per week of moderate-intensity aerobic activity (or 75–150 minutes vigorous), or equivalent combination. Resistance exercise 2 days per week.
Key Benefits: Reduces SBP by 5–7 mmHg, improves HDL-C, reduces TG, enhances insulin sensitivity, facilitates weight loss, reduces all-cause and CV mortality by ~30%. Even small amounts of activity reduce mortality risk.
Sedentary Time Reduction (Class IIa): Limit sitting; engage in light activity throughout day to reduce all-cause and CV mortality independent of formal exercise.
Nutrition & Diet
Recommended Dietary Approaches
Mediterranean Diet (Class I): Adopt to lower CVD risk. Emphasis on olive oil, vegetables, fruits, whole grains, legumes, nuts, fish. Evidence from PREDIMED trial shows 30% CV event reduction.
Saturated fats and trans fats; replace with unsaturated oils
Weight Management
Class I Maintenance of healthy body weight (BMI 18.5–24.9 kg/m²) fundamental for CV health. Weight loss of 5–10% in overweight/obese individuals reduces CV risk factors (BP, lipids, glucose) and mortality.
Physical activity: 150 min/week moderate activity or combined with resistance training
Behavioral support: Group programs, wearable trackers, mobile apps enhance adherence (Class IIa)
Bariatric surgery (Class IIa): Consider for high-risk obese individuals (BMI ≥35 with comorbidities or ≥40) when lifestyle fails
Smoking cessation + weight gain: CV benefits of quitting not negated by modest weight gain (Class I)
Smoking Intervention & Cessation
Evidence & Rationale
Class ISmoking cessation is strongly recommended for all smokers, regardless of weight gain; CV benefits outweigh any modest weight gain risk. Smoking accounts for ~50% of CVD deaths in smokers (~10% of all premature CVD mortality globally). CV risk in smokers is 5–7 times higher than non-smokers <50 years age. Even low-intensity passive smoking increases CV risk by ~30%. Risk persists ~8–10 years after cessation.
Cessation Strategies
Behavioral Support
Individual or group counseling, cognitive-behavioral therapy (CBT), motivational interviewing, telephone quitlines. Structured programs enhance success rates to ~15–30%.
Pharmacological Interventions (Class I)
Varenicline (Champix/Chantix): Partial nicotinic acetylcholine agonist. Dosing: 0.5 mg days 1–3, 0.5 mg BID days 4–7, 1 mg BID days 8–84. Most effective; 12-week quit rates ~35%. SE: nausea, vivid dreams, mood/psychiatric changes (monitor).
Nicotine Replacement Therapy (NRT): Patches (7–21 mg/day), gum (2–4 mg), lozenges, nasal spray, inhalers. Can combine forms (patch + gum for higher nicotine). 12-week quit rates ~18%. SE: local irritation, insomnia (with patch), hiccups (gum).
Combination Therapy: Varenicline + NRT or bupropion + NRT superior to monotherapy in some patients; increased quit rates to ~40–45%.
Electronic Cigarettes & Heat-Not-Burn Products
E-cigarettes and IQOS (heat-not-burn tobacco) may reduce harm vs. combustible cigarettes but are not risk-free. Nicotine dependence maintained; long-term CV safety unknown. Not recommended first-line; consider if traditional methods fail and patient motivated to switch.
Clinical Best Practices
Ask about smoking at every visit; provide cessation advice universally
Assess readiness to quit and motivation using 5R framework (Relevance, Risks, Rewards, Roadblocks, Repetition)
Set a quit date within 1–2 weeks of initiating pharmacotherapy
Combine behavioral + pharmacological support for best outcomes
Provide ongoing support (follow-up calls/visits at 3–7 days, 2 weeks, 1 month)
Manage relapse: most successful quitters try multiple times; retreatment encouraged
Diabetes Prevention & Type 2 DM Management
Type 2 Diabetes Prevention (Prediabetes)
Class I In persons at risk for type 2 DM (fasting glucose 100–125 mg/dL, 2-hour glucose 140–199 mg/dL post-OGTT, or HbA1c 39–47 mmol/mol):
Lifestyle modifications: Weight loss 5–10%, increased physical activity (150 min/week), Mediterranean diet. Diabetes Prevention Program trial showed 58% reduction in DM incidence over 3 years.
Metformin: 500–1000 mg daily for individuals unable to achieve/maintain lifestyle changes or with high-risk features. Reduces DM incidence by ~31%; additional CV and mortality benefits. SE: GI upset, vitamin B12 deficiency (rare, monitor).
Type 2 DM with Established ASCVD or High CV Risk
Class I Most type 2 DM patients are at high or very high CV risk. Intensive management of CV risk factors is paramount:
Glucose Control: Target HbA1c ~7% (53 mmol/mol) for most; individualize to avoid hypoglycemia. Less stringent targets (HbA1c 7–8%) for elderly, limited life expectancy, or frequent hypoglycemia.
BP Management: Target <140/90 mmHg (or <130/80 for established ASCVD); intensive BP lowering reduces CV events and HF
Lipid Management: High-dose statin ± ezetimibe; PCSK9i for high/very high-risk not achieving goals
Cardioprotective Agents (Class I): GLP-1RA (semaglutide, dulaglutide, liraglutide) or SGLT2i (empagliflozin, canagliflozin, dapagliflozin) with proven CV benefits for ASCVD or CKD. GLP-1RA reduces CV mortality and events. SGLT2i reduces HF hospitalizations and slows CKD progression.
Antithrombotic Therapy: Aspirin for secondary prevention; limited role in primary prevention without clear CV indications (Class IIb)
Type 1 DM: Always at elevated CV risk; intensive glucose control (HbA1c ~7%) reduces microvascular complications. Intensive glycemic control may increase hypoglycemia; individualize.
Type 2 DM + CKD: SGLT2i beneficial for renal outcomes; also reduces BP and weight. GLP-1RA beneficial for CV outcomes.
Type 2 DM + HF: SGLT2i reduces HF hospitalization regardless of diabetes status or LVEF
Antithrombotic Therapy
Aspirin in Primary Prevention
Class IIbAspirin has a limited role in primary prevention. Bleeding risk (major bleed ~1–2% annually) often outweighs CV benefit in apparently healthy low-risk individuals. Benefit-risk neutral or unfavorable in low-risk populations. Only consider very high-risk primary prevention (e.g., SCORE2 ≥7.5%) with absence of bleeding contraindications and informed patient consent.
Aspirin in Secondary Prevention
Class I For established ASCVD (CAD, prior MI, stroke/TIA, PAD), aspirin (75–100 mg daily) is a cornerstone of secondary prevention. Reduces recurrent events by ~25% relative to placebo. Absolute benefit outweighs bleeding risk in secondary prevention context.
Dual Antiplatelet Therapy (DAPT)
Class I Following acute coronary syndrome or percutaneous coronary intervention (PCI) with stent:
DAPT duration: Aspirin 75–100 mg daily indefinitely + P2Y12 inhibitor (clopidogrel 75 mg, prasugrel 5–10 mg, or ticagrelor 60–90 mg BID) for 12 months (or shorter for high bleeding risk)
Benefits: Reduces stent thrombosis and recurrent MI by ~25–35%
Bleeding risk: Major bleeding increased with DAPT; balance against ischemic benefit. Proton pump inhibitor may be added for GI protection if high bleeding risk.
Anticoagulation
For atrial fibrillation, mechanical heart valves, or VTE: direct oral anticoagulants (DOACs) or warfarin (INR 2–3) indicated based on condition. Combination aspirin + anticoagulation for specific indications (e.g., AF + acute MI) increases bleeding; weigh benefit-risk.
Psychosocial Factors & Mental Health
Depression & Mental Health Disorders
Class IMental disorders with significant functional impairment or decreased use of healthcare systems are considered as influencing CVD risk factors. Major depression increases CVD incidence by 1.5–2 fold and is associated with 2–3 fold increased CV mortality post-ACS and in HF.
Clinical Approach:
Screening: Use PHQ-9 (Patient Health Questionnaire-9) or GAD-7 (Generalized Anxiety Disorder-7) at baseline and periodically
Management (Class IIa): Antidepressive therapy (SSRI) should be considered for CHD with comorbid major depression. Sertraline, citalopram, escitalopram commonly used.
Psychotherapy: Cognitive-behavioral therapy (CBT), psychodynamic therapy, or interpersonal therapy effective for depression and anxiety
Structured Support: Group-based CR/prevention programs with psychosocial support improve outcomes and adherence
Avoid tricyclic antidepressants and antipsychotics in elderly or HF due to cardiac SE; SSRIs preferred
Psychosocial Stress & Stress Management
Class IIaASCVD patients with chronic stress should be referred to psychotherapeutic stress management programs to improve CV outcomes and reduce stress symptoms. Techniques include:
Cognitive-behavioral stress management (CBSM)
Relaxation training and biofeedback
Mindfulness-based interventions and yoga
Structured group programs and support groups
Social Support & Isolation
Social isolation and loneliness increase CVD risk and mortality by ~30%; comparable to smoking
Promote community engagement, family involvement, group-based rehabilitation
Telemedicine and remote monitoring may increase participation in prevention programs (especially during COVID)
Peer support networks and online communities supplement in-person support
Prevention in Disease-Specific Conditions
Chronic Kidney Disease (CKD)
Class I Patients with CKD are at high/very high CV risk due to shared risk factors (HTN, DM, dyslipidemia) and CKD-specific mechanisms (uremia, anemia, vascular calcification). Management priorities:
BP target <140/90 mmHg (consider <130/80 for ASCVD); ACEi/ARB preferred (renoprotective)
High-dose statin ± ezetimibe for lipid management
SGLT2i and/or GLP-1RA for renal and CV benefit (slows GFR decline, reduces proteinuria)
Smoking cessation, weight management, physical activity per guidelines
Monitor electrolytes and GFR with ACEi/ARB use; contraindicated if K+ >5.5 mEq/L or GFR <30 (relative)
Atrial Fibrillation (AF)
Class I AF increases stroke risk ~5 fold; stroke prevention with anticoagulation (CHA₂DS₂-VASc score ≥1 men, ≥2 women) recommended using DOACs or warfarin (INR 2–3). Additional management:
BP control <140/90 mmHg; more intensive control may reduce AF recurrence
Rate control with beta-blockers or CCB (target resting HR <110 bpm or more lenient control acceptable)
Rhythm control (antiarrhythmic drugs) for symptomatic patients; no mortality benefit vs. rate control
Identify and manage comorbidities (HF, CKD, DM) contributing to AF
Heart Failure (HF)
Class IComprehensive cardiac rehabilitation (CR) program recommended for HF patients. CR includes exercise training, education, psychological support, improving outcomes, reducing hospitalizations. Guideline-directed medical therapy:
HF with reduced EF (HFrEF): ACEi/ARB/ARNI, beta-blockers, aldosterone antagonists, SGLT2i all reduce mortality. Newer agents (vericiguat, omecamtiv mecarbil) for select patients.
HF with preserved EF (HFpEF): SGLT2i improves symptoms and hospitalization; limited other pharmacological options for mortality benefit
BP, glucose, lipid management per guidelines
ICD/CRT consideration for EF <35% and QRS ≥120 ms or clinical indication
Cerebrovascular Disease (Stroke/TIA)
Class I Secondary stroke prevention includes:
BP control target <140/90 mmHg; more intensive (<130/80) may further reduce recurrent stroke risk
Antiplatelet therapy: aspirin 75–325 mg daily for non-cardioembolic stroke; clopidogrel or aspirin + extended-release dipyridamole alternatives
Anticoagulation for cardioembolic stroke (AF, mechanical valve, recent MI with LV thrombus)
Statin therapy for LDL-C <1.8 mmol/L (70 mg/dL) or ≥50% reduction
Glucose control (target HbA1c ~7%); insulin preferable to oral agents in acute stroke
Smoking cessation, weight management, physical activity, diet (Mediterranean) per guidelines
Carotid revascularization (endarterectomy or stent) for symptomatic severe stenosis (70–99% stenosis); asymptomatic stenosis management individualized
Peripheral Artery Disease (PAD)
Class I Best medical therapy for secondary prevention:
Statin therapy for LDL-C <1.8 mmol/L (70 mg/dL) or ≥50% reduction
ACEi or ARB (cardioprotective); reduce CV and limb events
Revascularization (endovascular or surgical) reserved for symptomatic limb-threatening ischemia or disabling claudication refractory to medical therapy
Chronic Obstructive Pulmonary Disease (COPD)
COPD increases CVD risk by ~1.5–2 fold due to systemic inflammation, oxidative stress, and shared risk factors (smoking). Aggressive CV risk factor management essential: BP control, lipid management, smoking cessation, physical activity/pulmonary rehabilitation. COPD exacerbations increase CV events.
Delay BP treatment in hypertensive patients; combine pharmacotherapy with intensive lifestyle modifications
Prescribe antiarrhythmics for rate control in AF without clear symptom-driven indication; beta-blockers, CCBs preferred
Initiate triple antithrombotic therapy (aspirin + DAPT) without specific indication; increases bleeding risk substantially
Discourage very low LDL-C targets in very high-risk patients; LDL-C <1.4 mmol/L safe and beneficial
Overlook comorbidities (depression, CKD, COPD, AF) that modify CV risk and require targeted interventions
Neglect lifestyle modifications; they are foundational and complement pharmacotherapy
Start medication without assessing barriers to adherence; address cost, complexity, side effects proactively
CVD Risk Calculators & Assessment Tools
Interactive online and mobile calculators enable clinicians and patients to estimate 10-year and lifetime CVD risk, explore treatment benefits, and facilitate shared decision-making. The following calculators are available and recommended: