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8 December 2015
Multifactorial approach the key to managing high cardiovascular risk
Multifactorial preventive approaches targeting seven key modifiable cardiovascular risk factors had prompt beneficial effect in high risk patients in general practice.
Avanzini F, Marzona I, Baviera M et al; Risk and Prevention Study Collaborative Group. Improving cardiovascular prevention in general practice: Results of a comprehensive personalized strategy in subjects at high risk. Eur J Prev Cardiol 2015 [Epub ahead of print]
Objective: To assess the feasibility and effectiveness of a comprehensive personalized method for cardiovascular prevention in high risk patients followed by their general practitioner
Study design: Multicentre, general practice trial. The duration of follow-up was 5 years.
Study population: 12,513 patients (mean age 64.0 ± 9.5 years; 61.5% male) with multiple cardiovascular risk factors (68.7%) or history of atherosclerotic disease (29.5%). With respect to lipids, mean baseline low-density lipoprotein cholesterol (LDL-C) was 132 ± 36 mg/dL and triglycerides were 150 mg/dL (range 100-200 mg/dL).  Overall, 41% of patients were on statins.
Primary outcome:

Control of the seven major modifiable cardiovascular risk factors (hypertension, hypercholesterolaemia, diabetes, obesity, smoking, unhealthy diet, physical inactivity) during follow-up, as defined by the cardiovascular health metrics score. Calculation of this score was based on how many of these seven major modifiable risk factors were well controlled at baseline and follow-up. The goals for control were:

blood pressure <140/90mmHg

LDL-C <130 mg/dL or fasting total cholesterol <200 mg/dL

fasting blood glucose <130 mg/dL or HbA1c <7%

body mass index <30 kg/m2

Nonsmoker; regular physical activity; healthy diet

Secondary outcome:

Incidence of cardiovascular deaths and hospitalization for cardiovascular reasons according to improvement in the global cardiovascular risk profile during the first year.


At baseline and at each year of follow-up, the presence and control of all major modifiable cardiovascular risk factors was assessed. Improvement in global cardiovascular risk was assessed using the absolute difference between the cardiovascular health metrics score at the one-year and at baseline.


Multivariable Cox proportional hazards was used to investigate the association between the cardiovascular health metrics score at baseline and major cardiovascular events during follow-up, adjusting for age, sex, history of cardiovascular risk factors, cardiovascular disease and cardiovascular medications.

Main results:

·       1478 (12%) patients had cardiovascular events during follow-up; the risk of an event was inversely related to the cardiovascular health metrics score at baseline (p=0.011).

·       Control of all major modifiable risk factors except physical inactivity improved significantly (p<0.0001) during follow-up.

·       Improvement in the control of one cardiovascular risk factor after the first year of follow-up was associated with 6% lower incidence of cardiovascular events in the next 4 years (hazard ratio 0.939, 95% CI 0.887–0.994; p=0.03).

Authors’ conclusion: Our comprehensive, personalized method for cardiovascular risk prevention in people at high risk appears feasible in general practice. The improvement in the global cardiovascular risk profile was associated with a better prognosis.


This large general practice study reaffirms the importance of a multifactorial approach to cardiovascular prevention in high-risk individuals. Improvement in the control of one of the seven major modifiable risk factors after one year resulted in 6% reduction in the risk of an event over the following 4 years. The findings of this study are strengthened by the large cohort size, including a broad range of patients representative of those seen routinely in general practice, as well as the study methodology and metrics, which could be readily translated to routine primary care.

 On further inspection, a substantial proportion of this population was also at high cardiometabolic risk as 60% had diabetes and 49% were obese. Thus it is likely that atherogenic dyslipidaemia would also be prevalent in this group (1); indeed, the upper limit of the range for triglycerides was 200 mg/dL with a mean of 150 mg/dL, suggesting that this is likely to be the case. While targeting LDL-C is the primary target of preventive lipid-lowering strategies (2,3), it is increasingly clear that therapeutic intervention against atherogenic dyslipidaemia, especially in patients with cardiometabolic disease, is also needed, supported by accumulating evidence of the atherogenicity of triglyceride-rich lipoproteins and their remnants, even when LDL-C is controlled by statins  (4). Increasingly, the evidence-base for this risk factor warrants consideration in updates to guidelines.

 The Residual Risk Reduction Initiative (R3i) congratulates the authors of this study. The R3i believes that such a metric based on key major modifiable cardiovascular risk could be readily adapted to include atherogenic dyslipidaemia in relevant high risk groups.


1. Kotseva K, Jennings CS, Turner EL, Mead A, Connolly S, Jones J, Bowker TJ, Wood DA; ASPIRE-2-PREVENT Study Group. ASPIRE-2-PREVENT: a survey of lifestyle, risk factor management and cardioprotective medication in patients with coronary heart disease and people at high risk of developing cardiovascular disease in the UK. Heart 2012;98:865-71..

2. Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32:1769-818.

3. Perk J, De Backer G, Gohlke H et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012;33:1635-701.

4. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet 2014;384:626-35.

Key words cardiovascular risk; cardiovascular prevention; general practice trial