Summary
Background
Controlling low-density lipoprotein (LDL)-cholesterol concentration is of tremendous importance to reduce cardiovascular risk.
Aims
To investigate the attainment of LDL-cholesterol targets recommended in French and European guidelines on cardiovascular prevention, according to levels of cardiovascular risk.
Methods
Participants aged 35 to 74 years ( n = 4609) were randomly selected from the general population of three French regions. A standardized data collection was performed to assess cardiovascular risk as described in the French and European guidelines.
Results
Overall, 17.5% of participants were considered to be at high risk and 25.4% at high or very high risk, according to the French and European guidelines, respectively. Only 1.2% of participants with no cardiovascular risk factors according to the French guidelines had an LDL-cholesterol concentration above the recommended target, whereas 82.5% of high-risk subjects did not attain their goal (70.8% among high-risk subjects receiving lipid-lowering therapy). Among untreated people, the median reduction in LDL-cholesterol needed to reach target ranged from 6.6% (lowest-risk groups) to 36.0% (highest-risk subjects). When risk was classified according to the European guidelines, the majority of participants did not reach the recommended LDL-cholesterol targets, irrespective of their level of risk or lipid-lowering therapy.
Conclusion
In a majority of primary prevention candidates with multiple risk factors and in most high-risk subjects, LDL-cholesterol targets recommended by French guidelines are not being achieved, either because of insufficient treatment or because subjects are not recognized as being at risk. More stringent targets proposed by the European guidelines are not being achieved in most cases.
Résumé
Contexte
Le contrôle du cholestérol-LDL est primordial pour réduire le risque cardiovasculaire.
Objectifs
Décrire l’atteinte des objectifs fixés par les recommandations françaises et européennes pour le cholestérol-LDL, en fonction du niveau de risque cardiovasculaire.
Méthodes
Les participants, âgés de 35 à 74 ans ( n = 4609) ont été tirés au sort dans la population générale de trois régions françaises. Un recueil de données standardisé a été effectué pour déterminer le niveau de risque cardiovasculaire, tel que décrit dans les recommandations françaises et européennes.
Résultats
L’échantillon comprenait 17,5 % de participants à haut risque (recommandations françaises) et 25,4 % de sujets à haut ou très haut risque (recommandations européennes). Seulement 1,2 % des participants sans facteur de risque (recommandations françaises) avaient un taux de cholestérol-LDL au-dessus de l’objectif. En revanche, 82,5 % des sujets à haut risque n’étaient pas à l’objectif (70,8 % des sujets à haut risque sous traitement hypolipémiant). Parmi les sujets non traités, la réduction médiane de cholestérol-LDL nécessaire pour atteindre l’objectif, variait de 6,6 % (sujets les moins à risque) à 36,0 % (haut risque). Lorsque le risque était défini selon les critères européens, la majorité des participants n’atteignait pas l’objectif, qu’il y ait ou non prise d’un traitement hypolipémiant.
Conclusion
La majorité des sujets à haut risque ou cumulant les facteurs de risque n’est pas à l’objectif, soit du fait d’un traitement insuffisant, soit parce que les sujets ne sont pas identifiés comme étant à risque. Cela est encore plus marqué si l’on considère les objectifs des recommandations européennes.
Background
Current guidelines for the prevention and treatment of cardiovascular disease emphasize the importance of treating multiple risk factors, including dyslipidaemia and hypertension, depending on the patient’s overall level of risk . This approach is also recommended in the most recent evidence-based review on dyslipidaemia management from the French health agency (Haute Autorité de santé) . The potential impact of lipid-lowering therapy on the prevalence of dyslipidaemia in France has been highlighted by epidemiological data from the MONItoring of trends and determinants in CArdiovascular disease (MONICA) project, which were obtained in 1996–1997, and the MONA LISA (MOnitoring NAtionaL du rISque Artériel) survey, which was conducted between 2006 and 2007 . These studies showed significant decreases in low-density lipoprotein (LDL)-cholesterol concentrations and dyslipidaemias over a 10-year period, concurrent with the increasing use of lipid-lowering therapy, particularly statins .
Despite the existence of numerous national and international guidelines for the management of dyslipidaemia, several studies have shown that management is often suboptimal in Europe . Besides, prevalence of cardiovascular risk factors is still substantially elevated in France . The aim of this analysis from the MONA LISA study was to investigate, in the French general population, the attainment of LDL-cholesterol targets in subjects at various levels of cardiovascular risk, as defined in the most recent French and European guidelines.
Methods
Details of the MONA LISA survey have been published previously . Participants aged 35 to 74 years were recruited between 2006 and 2007 from the general population in three regions of France: the Lille urban community in Northern France, the Bas-Rhin department in Eastern France and the Haute-Garonne department in South West France. The participants were selected randomly from electoral rolls after stratification by town size, sex and age, in order to achieve a sample size of 200 of each sex in each age group (35–44 years, 45–54 years, 55–64 years, 65–74 years) and each region. In accordance with French law, the study protocol was approved by the appropriate independent ethics committee and written informed consent was obtained from all participants.
Included subjects responded to a standardized questionnaire, covering demographic variables, socioeconomic status, medical history and drug intake, and underwent a standardized physical examination. Blood pressure was measured twice, at rest, with a standard sphygmomanometer (OMRON ® 705IT). A 20 mL blood sample was collected into a disodium ethylene-diamine-tetraacetic acid tube after an overnight fast (at least 10 h) and plasma was separated by centrifugation within 4 h. Cholesterol and triglyceride concentrations were measured by enzymatic assays (Olympus, Melville, NY, USA), and glucose was measured by the standard glucose hexokinase assay (DuPont Dimension, Brussels, Belgium). High-density lipoprotein (HDL)-cholesterol was assessed after sodium phosphotungstate/magnesium chloride precipitation (Olympus); LDL-cholesterol was determined by the Friedewald equation if triglyceride concentrations were less than 4.6 mmol/L (4 g/L). All biological measurements were performed in a core laboratory (Institut Pasteur de Lille).
Assessment of cardiovascular risk
For each participant, the presence of cardiovascular risk factors (family history of premature coronary heart disease [CHD], hypertension, smoking, dyslipidaemia or diabetes) was recorded and the global cardiovascular risk was calculated using established scoring systems . A family history of premature CHD was defined as the occurrence of a myocardial infarction in the participant’s father before the age of 55 years or in the participant’s mother before 65 years. Smoking referred to current smoking (any type of smoking: cigarettes, cigars, pipe) or past smoking stopped within the previous 3 years. Hypertension was defined as a resting blood pressure of greater or equal to 140/90 mmHg (mean of two measurements) or greater or equal to 130/80 mmHg among people with diabetes or an estimated glomerular filtration rate (eGRF) less than 60 mL/min/1.73 m 2 (evaluated by the Modification of Diet in Renal Disease formula) or the use of antihypertensive medications. Hypercholesterolaemia was defined as an LDL-cholesterol concentration greater or equal to 4.1 mmol/L (1.6 g/L) or the use of lipid-lowering medication with triglyceride concentration less than 1.7 mmol/L (1.5 g/L); hypertriglyceridaemia or combined dyslipidaemia were defined as triglyceride concentration greater or equal to 1.70 mmol/L (1.5 g/L) and low HDL-cholesterol was defined as a concentration less than 1 mmol/L (0.4 g/L). Diabetes was defined as a fasting blood glucose concentration greater or equal to 7 mmol/L (1.26 g/L) or the use of hypoglycaemic drug treatment.
The 10-year risk of CHD (corresponding to the probability of a given subject developing CHD in the next 10 years) was calculated using the Framingham algorithm and the 10-year risk of fatal cardiovascular disease (death caused by any arterial disease, including coronary, cerebrovascular and other artery diseases, and sudden death) was estimated using the Systematic Coronary Risk Evaluation (SCORE) system .
The level of risk was also scored according to the French guidelines, based on the number of risk factors present . These risk factors were: age (≥ 50 years in men and ≥ 60 years in women), family history of premature CHD, current or past smoking as defined above, hypertension, diabetes and low HDL-cholesterol. The total number of risk factors was reduced by one if the HDL-cholesterol concentration was greater than 1.6 mmol/L (0.6 g/L). Subjects were considered to be at high risk if they had documented cardiovascular disease (coronary heart disease, cerebrovascular disease, aortic aneurysm or atherosclerosis affecting the aorta or leg arteries), diabetes and eGFR less than 60 mL/min/1.73 m 2 or diabetes with at least two other risk factors or a 10-year risk of CHD of at least 20%.
The level of risk was also estimated according to the 2012 guidelines for cardiovascular prevention from the European Society of Cardiology (ESC) . Subjects were considered to be at low risk if their SCORE rating was less than 1% (corresponding to a 10-year probability of cardiovascular mortality of less than 1%), and they were categorized at moderate risk if SCORE was greater or equal to 1% and less than 5%. Subjects with markedly elevated single risk factors (arterial blood pressure greater or equal to 180/110 mmHg or LDL-cholesterol greater or equal to 5.7 mmol/L [2.2 g/L]) were categorized at high risk, as well as those with diabetes (without associated cardiovascular risk factors), moderate chronic kidney disease (eGFR ranging between 30 and 59 mL/min/1.73 m 2 ), or a SCORE rating greater or equal to 5% and less than 10%. Subjects at very high risk were those with documented cardiovascular disease (as detailed above), severe chronic kidney disease (eGFR less than 30 mL/min/1.73 m 2 ), diabetes with one or more associated cardiovascular risk factor(s), diabetes with eGFR less than 60 mL/min/1.73 m 2 or subjects with a SCORE rating greater or equal to 10%.
Targets for LDL-cholesterol according to levels of cardiovascular risk
According to French guidelines , LDL-cholesterol should be less than 5.7 mmol/L (2.2 g/L) in subjects with no associated risk factors, less than 4.9 mmol/L (1.9 g/L), 4.1 mmol/L (1.6 g/L), and 3.4 mmol/L (1.3 g/L) in those with one, two and three associated risk factors, respectively, and less than 2.6 mmol/L (1.0 g/L) in high-risk subjects. According to the ESC guidelines , targets for LDL-cholesterol are 3 mmol/L (1.15 g/L) in people at low or moderate risk, 2.6 mmol/L (1.0 g/L) in those at high risk and 1.8 mmol/L (0.7 g/L) in subjects at very high-risk.
Statistical analysis
Continuous variables were summarized as mean ± standard deviation or median (interquartile range) for non-normally distributed variables. Categorical variables were presented as absolute numbers, with percentages and 95% confidence intervals. The percentage of subjects in whom LDL-cholesterol targets were not achieved was estimated in the overall sample and subsequently in participants who were and were not receiving lipid-lowering therapy. In the overall sample, this percentage was also estimated after direct standardization, using the 2009 French population to provide a reference distribution for age and sex. The percentage reduction required to meet the LDL-cholesterol target in a given subject was calculated as:
LDL-cholesterol − LDL-cholesterol target LDL-cholesterol level × 100
All analyses were performed with SAS ® software (SAS Institute, Cary, NC, USA), except for standardized estimates, which were computed with STATA ® software (STATA Corporation, College Station, TX, USA).
Results
Study population
Participation rates in the MONA LISA study were 50% for men and 51% for women, resulting in a total of 4769 participants aged 35 to 74 years, of whom 4609 were included in the present analysis. Overall, 160 participants (3.4%) were excluded: LDL-cholesterol could not be estimated in 56 subjects because triglyceride concentrations were greater or equal to 4.6 mmol/L (4 g/L), 26 subjects provided a non-fasting blood sample and data on cardiovascular risk factors were missing in 78 subjects.
Demographic characteristics, cardiovascular risk factors and global levels of cardiovascular risk for the included participants are summarized in Table 1 . Approximately 50% of the participants were hypertensive and 53.6% had hypercholesterolaemia, hypertriglyceridaemia or combined dyslipidaemia. The mean LDL-cholesterol in the overall population was 3.63 ± 0.91 mmol/L (1.41 ± 0.35 g/L). In total, 946 subjects were receiving treatment with lipid-lowering drugs; of these, 78.4% received a statin, 19.1% a fibrate and 2.5% were treated with another lipid-lowering therapy. A total of 1615 subjects (35.0%) had no associated cardiovascular risk factors (i.e. no risk factors except possibly high LDL-cholesterol, as defined in the French guidelines ), but 178 (3.9%) had three or more associated risk factors and 808 (17.5%) were considered to be at high risk. Similarly, when risk was assessed according to the ESC guidelines , 14.1% and 11.3% were considered to be at high or very high risk, respectively. The median 10-year risks of CHD and fatal cardiovascular disease were 7.5% and 0.60%, respectively.
