Table 1

Therapeutic targets for traditional CVRFs based on the corresponding two time periods of the study 2012 and 2016 ESC guidelines for CVD prevention in the general population and on 2013 ESC guidelines on diabetes, prediabetes and CVDs in collaboration with the EASD for patients with DM

	Therapeutic targets for traditional cardiovascular risk factors
CVD risk factors	2012 ESC guidelines for CVD prevention	2016 ESC guidelines for CVD prevention	2013 ESC guidelines on diabetes, prediabetes and CVDs in collaboration with the EASD	2021 ESC guidelines for CVD prevention*
Smoking	No current smoking	No current smoking	No current smoking	No current smoking
Physical activity	At least 150 min /week (healthy adults of all ages should spend 2.5–5 hours a week on physical activity or aerobic exercise training of at least moderate intensity, or 1–2.5 hours a week on vigorous intense exercise)	At least 150 min/week of moderate aerobic physical activity (30 min for 5 days/week) or 75 min/week of vigorous aerobic physical activity (15 min for 5 days/week) or a combination thereof	Moderate to vigorous physical activity of ≥150 min/week is recommended for the prevention of CVD in DM	At least 150–300 min/week of moderate intensity or 75–150 min/week of vigorous intensity aerobic physical activity, or an equivalent combination thereof
Body weight	BMI 20–25 kg/m² and waist circumference ≥94 cm in men and ≥80 cm in women represents the threshold at which no further weight should be gained	BMI 20–25 kg/m² and waist circumference <94 cm (in men) and <80 cm (in women)	BMI 20–25 kg/m² and waist circumference ≥94 cm in men and ≥80 cm in women represents the threshold at which no further weight should be gained	a reduction in weight is recommended for overweight and obese people to improve CVD risk profile (even a moderate weight loss of 5%–10% from baseline is beneficial) Waist circumference ≥94 cm in men and ≥80 cm in women: no further weight gain Waist circumference ≥102 cm in men and ≥88 cm in women: weight reduction advised
BP	Systolic BP should be lowered to <140 mm Hg (and diastolic BP to <90 mm Hg) in all hypertensive patients	Systolic BP should be lowered to <140 mm Hg and diastolic BP to <90 mm Hg	The main aim when treating hypertension in patients with DM should be to lower BP to <140/85 mm Hg. In case of nephropathy: target systolic BP <130/<140 mm Hg in patients with/without proteinuria	The first objective of treatment is to lower BP to <140/90 mm Hg in all patients and subsequent BP targets are tailored to age and specific comorbidities: In treated patients aged 18–69 years, it is recommended that systolic BP should ultimately be lowered to a target range of 120–130 mm Hg In treated patients aged ≥70 years, it is recommended that systolic BP should generally be targeted to <140 and down to 130 mm Hg if tolerated In all treated patients, diastolic BP is recommended to be lowered to <80 mm Hg
LDL cholesterol (primary target)	Target LDL according to CVD risk category: Low-risk tomoderate-risk patients: <115 mg/dL High-risk patients: <100 mg/dL Very high-risk patients: <70 mg/dL	Target LDL according to CVD risk category: Low-risk to moderate-risk patients: <115 mg/dL High-risk patients: <100 mg/dL or a reduction of at least 50% if the baseline is between 100 and 200 mg/dL Very high-risk patients: <70 mg/dL or a reduction of at least 50% if the baseline is between 70 and 135 mg/dL	Target LDL according to CVD risk category: High-risk patients:<100 mg/dL Very high-risk patients:<70 mg/dL or at least a ≥50% LDL-C reduction if this target goal cannot be reached	Target LDL according to age and CVD risk category: 40–69 years old: initial goal of LDL <100 mg/dL and as second step target LDL <70 mg/dL and ≥50% reduction in high-risk patients and LDL <55 mg/dL and ≥50% reduction in very high-risk patients ≥70 years old: initial goal of LDL <100 mg/dL. Frailty, polypharmacy and muscle symptoms remain relevant factors to consider in older patients. Patients with CKD: initial goal of LDL <100 mg/dL and ≥50% reduction and as a second step target LDL <70 mg/dL in high-risk patients and LDL <55 mg/dL in very high-risk patients Patients with type II DM: (a) without CVD and/or severe target organ damage: initial goal of LDL <100 mg/dL and as second step target LDL <70 mg/dL and ≥50% reduction, (b) with established CVD and/or severe target organ damage: initial goal of LDL <70 mg/dL and as second step target LDL <55 mg/dL and ≥50% reduction Patients with established CVD: initial goal of LDL <70 mg/dL and ≥50% reduction and as second step target LDL <55 mg/dL
HDL-C	Νo target but >40 mg/dL in men and >45 mg/dL in women shows lower risk	No target but >40 mg/dL in men and >45 mg/dL in women indicate lower risk	–	No specific goals for HDL-C levels have been determined in clinical trials, although low HDL-C is associated with (residual) risk in patients with CVD
Triglycerides	Νo target but <150 mg/dL shows lower CVD risk	No target but <150 mg/dL indicates lower risk and higher levels indicate a need to look for other risk factors	No target but <150 mg/dL shows lower CVD risk	No target but <150 mg/dL indicates lower risk and higher levels indicate a need to look for other risk factors
HbA1c	–	–	Target HbA1c <7%	For patients with DM, target HbA1c <7%

*The 2021 ESC guidelines are presented only for comparsion reasons; they weren’t used in the analysis because all patients in the study were enrolled between 2011 and 2020.
BMI, body mass index; BP, blood pressure; CKD, chronic kidney disease; CVD, cardiovascular disease; EASD, European Association for the Study of Diabetes; ESC, European Society of Cardiology; HbA1c, haemoglobin A1c; HDL-C, high-density lipoprotein cholesterol; LDL, low-density lipoprotein.