Summary
Background
Residual dyslipidaemia in patients treated with statins needs to be addressed to reduce the prevalence of cardiovascular disease in primary and secondary care.
Aims
To estimate the prevalence of residual lipid abnormalities in statin-treated patients in France.
Methods
Plasma concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides were recorded in patients classified by cardiovascular risk according to guidelines from Agence française de sécurité sanitaire des produits de santé . Recruitment took place between September 2008 and February 2009, and involved patients aged > 45 years who had been on statin therapy for ≥ 3 months.
Results
Overall, 39.6% of the 4335 statin-treated patients had lipid values within desirable levels. Low-density lipoprotein cholesterol was not at goal more often (51.8%) in higher risk patients than in all patients averaged (37.2%). Also, high-risk patients with low-density lipoprotein cholesterol not at goal had additional lipid abnormalities (low high-density lipoprotein cholesterol and/or high triglycerides) more frequently (25.6%) than all patients averaged (18.4%).
Conclusion
We conclude that a significant proportion of dyslipidaemic patients at high cardiovascular risk in France are not achieving treatment goals after statin treatment. A significant proportion of these patients might benefit from alternative therapies targeted at improving low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglyceride levels. More attention to the management of these patients is needed to use public health resources more effectively.
Résumé
Contexte
Les anomalies lipidiques résiduelles chez les patients traités par statines doivent être reconnues afin de diminuer la prévalence de la maladie cardiovasculaire.
Objectifs
Cette étude a été menée afin d’estimer la prévalence des anomalies lipidiques résiduelles chez des patients traités par statines en France.
Méthodes
Les concentrations plasmatiques du LDL-cholestérol, du HDL-cholestérol et des triglycérides ont été analysées chez les patients selon la classification du risque établie par l’Afssaps. Le recrutement s’est déroulé de septembre 2008 à fevrier 2009, incluant des patients agés de 45 ans ou plus et sous statines depuis plus de trois mois.
Résultats
Au total, 39,6 % des 4335 patients traités par statines ont des valeurs biologiques lipidiques dans les valeurs souhaitables. Le LDL-cholestérol n’était pas à l’objectif thérapeutique plus souvent (51,8 %) chez les sujets à haut risque par rapport à l’ensemble de l’échantillon (37,2 %). De plus, les sujets à haut risque qui n’étaient pas à l’objectif thérapeutique pour le LDL-cholestérol avaient des anomalies lipidiques complémentaires (cholestérol HDL bas ou triglycérides élevés) plus fréquemment (25,6 %) par rapport à l’ensemble des patients (18,4 %).
Conclusions
Une part significative des patients traités par statines en France et à haut risque ne sont pas aux objectifs thérapeutiques recommandés. Certains de ces patients pourraient bénéficier de thérapeutiques complémentaires destinées à améliorer le LDL-cholestérol, le HDL-cholestérol ou les triglycérides. Une attention particulière doit être réservée à ces patients afin d’utiliser les ressources de santé plus efficacement.
Background
Lowering the prevalence of modifiable risk factors such as dyslipidaemia, smoking or sedentary lifestyle has contributed to reducing cardiovascular-related mortality . In urban France, cardiovascular disease is the most frequent cause of death in women and the second most frequent in the general population, only recently surpassed by cancer .
It is estimated that reduction of plasma cholesterol alone prevented 24% of cardiovascular disease-related deaths between 1980 and 2000 in the United States . Many other studies have similarly shown the benefits of lipid-lowering treatments not only on mortality but also on morbidity . High circulating low-density lipoprotein (LDL) cholesterol levels are most successfully treated with statins . Every 1 mmol/L reduction in LDL cholesterol is linked to a 24% decrease in mortality .
Residual dyslipidaemia remains for a significant number of treated patients. Some patients do not reach the intended therapeutic goals for LDL cholesterol . Significant risk associated with other lipid parameters represents additional normal levels to be achieved. Thus, another group of dyslipidaemic patients at risk despite treatment are those with low levels of high-density lipoprotein (HDL) cholesterol and/or high levels of triglycerides . Low HDL cholesterol is in itself an established independent risk factor and high triglycerides may be too, although this is controversial . Statins are known to mildly augment blood levels of HDL cholesterol (4–8%) and to reduce triglycerides (10–35% depending on baseline triglyceride levels) .
The Dyslipidemia International Study (DYSIS) was an epidemiological study recently conducted in Europe and Canada with the objective of evaluating the prevalence of residual lipid abnormalities in patients receiving statin therapy. In the present report, we perform a separate analysis on the DYSIS cohort from France. The aim was to estimate the prevalence of different types of dyslipidaemia according to the guidelines of the Agence française de sécurité sanitaire des produits de santé (Afssaps).
Methods
Study population
As part of DYSIS, subjects were enrolled at 740 sites in France. The sample included outpatients managed by a family practitioner or referred to a specialist (endocrinologist or cardiologist) for the treatment of dyslipidaemia.
Eligible subjects were individuals older than 45 years, who had been on statin therapy for 3 months or longer and had at least one fasting blood lipid profile within the past 6 months available while receiving statin therapy. Patients participating in other clinical studies were excluded from our study. Each site was allowed to enrol up to 10 consecutive patients.
Study design and data collection
This was a cross-sectional study designed to estimate the prevalence of different types of dyslipidaemia in statin-treated patients. The study protocol was approved by the relevant local ethical review committees. Patients who visited physicians, irrespective of the reason, and fulfilled the inclusion criteria were invited to participate. They were informed of both the aims of the study and its protocol. Data were collected from a single clinical examination and from medical charts.
Information was recorded on patient demographic data (sex, age), type of medical practice and location. Other clinical variables collected were: history of premature cardiovascular disease in first-degree relatives, smoking history, hypertension, ischaemic heart disease, diabetes mellitus, cerebrovascular disease, peripheral artery disease, height, weight, waist circumference, level of physical activity, alcohol consumption, fasting plasma glucose and HbA1c. Following the definition of the International Diabetes Federation, metabolic syndrome was considered to be present if a person had central obesity (waist circumference ≥ 94 cm for Europid men and ≥ 80 cm for Europid women, with ethnicity specific values for other groups) plus any two of the following: triglycerides ≥ 1.7 mmol/L (150 mg/dL) or specific treatment for this lipid abnormality; HDL cholesterol < 1.0 mmol/L (40 mg/dL) in men and < 1.29 mmol/L (50 mg/dL) in women or specific treatment for this lipid abnormality; systolic blood pressure (BP) ≥ 130 or diastolic BP ≥ 85 mmHg or treatment of previously diagnosed hypertension; and fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL) or previously diagnosed type 2 diabetes.
For this evaluation of the French population, patients were distributed into five risk categories, following the criteria set forth by the Afssaps . Each category is defined by the sum of risk factors applicable to an individual: 0, 1, 2, ≥ 3 or high risk. High-risk patients were considered as those with either proven coronary disease, or with diabetes plus two other cardiovascular risk factors. Cerebrovascular and peripheral arterial diseases, considered here as separate disease entities, were present only in patients at high risk.
Information collected on statin therapy included the name and daily dose of the statin and any other lipid-modifying therapies used at the time of the blood lipid tests.
Laboratory results from patients, who had been on statin therapy for 3 or more months, were included in the analyses. Plasma lipid tests included in this study were: total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, all expressed in mmol/L and in mg/dL. The results were analysed in the light of specific targets for every risk level, as recommended by the French guidelines for prevention of cardiovascular risk (see below). The percentages of patients within the therapeutic normal levels (i.e., at goal) for single and combined lipid measurements are presented in Venn diagrams.
The recommendations from the Afssaps to define the LDL-cholesterol targets were: in the absence of other risk factors, the target LDL cholesterol for an individual is 5.7 mmol/L (220 mg/dL); for patients with 1, 2, or ≥ 3 risk factors, it is 4.9, 4.1 and 3.4 mmol/L (190, 160 and 130 mg/dL), respectively; and for high-risk patients, the target is 2.6 mmol/L (100 mg/dL). HDL cholesterol below 1.0 mmol/L (40 mg/dL) is a risk factor for both men and women. By contrast HDL cholesterol values > 1.5 mmol/L (60 mg/dL) are considered protective and computed as (−1) in the risk calculation equation. As no recommended threshold for plasma triglyceride concentrations is given in the Afssaps guidelines, the one recommended (1.7 mmol/L [150 mg/dL]) by the European Society of Cardiology was used.
Statistical analysis
Sample-size estimations for a binomial proportion of prevalence of dyslipidaemia between 20 and 60% indicated that a survey on 4000 individuals would allow prevalence estimations with precisions of between 1 and 2.5%.
Continuous variables, including patient characteristics, are reported using descriptive statistics (mean ± standard deviation [SD] or median with Q1–Q3 interquartile range, as appropriate). Categorical variables are presented as percentage and absolute number. The percentages of patients classified in the five risk categories were used to stratify the results for LDL cholesterol, HDL cholesterol and triglycerides by risk category. Post-hoc analyses compared subgroups of combined lipid abnormalities (i.e., LDL cholesterol not at goal, low HDL cholesterol and/or high triglycerides) by risk level. Distributions of single and multiple combined lipid abnormalities were obtained and the prevalence of each lipid profile was calculated.
All analyses were performed with the Statistical Analyzing System, version 9.1 (SAS Institute Inc., Cary, NC, USA). Patients who did not have values for the appropriate lipid parameters were not included in the lipid analyses.
Results
Patient characteristics
A total of 4335 patients were recruited between September 2008 and February 2009, 69.5% of whom came from primary care centres. Mean age was 64.7 years and 65.3% were men. According to the risk-category classification of the Afssaps, 61.6% of the participants were considered at high risk, whereas only 5.9% had no additional risk factor ( Table 1 ). The most frequent clinical feature was hypertension (69.5% of patients), with a mean systolic and diastolic BP in this cohort of 134.0 ± 12.4 and 77.9 ± 8.3 mmHg, respectively. Metabolic syndrome was seen in 59.6% of the patients, coronary heart disease in 34.0%, diabetes in 32.9%, family history of premature cardiovascular disease in 26.9% and obesity in 26.8%. The mean waist circumference of the group was 98.9 ± 13.4 cm and the body mass index was 27.9 ± 4.8 kg/m 2 . Clinical characteristics and their distribution across risk groups are given in Table 1 .
| Variable | All patients | Patients with risk factors or at high risk | ||||
|---|---|---|---|---|---|---|
| 0 RF | 1 RF | 2 RF | ≥ 3 RF | High risk | ||
| N (%) | 4335 | 257 (5.9) | 552 (12.7) | 551 (12.7) | 186 (4.3) | 2669 (61.6) |
| Age a (years) | 64.7 (10.1) | 57.2 (9.3) | 62.4 (10) | 62.6 (9.0) | 60.6 (8.1) | 66.9 (9.8) |
| SBP a (mmHg) | 134.0 (12.4) | 129.8 (9.4) | 132.9 (11.0) | 134.3 (11.2) | 136.0 (9.8) | 134.4 (13.3) |
| DBP a (mmHg) | 77.9 (8.3) | 77.0 (6.8) | 77.7 (7.7) | 78.4 (7.9) | 80.9 (7.6) | 77.8 (8.6) |
| Waist circumference a (cm) | 98.9 (13.4) | 92.0 (12.5) | 95.2 (13.5) | 97.6 (12.3) | 100.7 (13.3) | 100.6 (13.3) |
| BMI a | 27.9 (4.8) | 25.6 (4.1) | 26.8 (4.6) | 27.7 (5.0) | 28.4 (4.1) | 28.4 (4.8) |
| BMI ≥ 30 kg/m 2 b (%) | 26.8 | 11.3 | 19.8 | 22.7 | 33.5 | 30.5 |
| Women b (%) | 34.7 | 61.1 | 52.4 | 40.8 | 31.2 | 27.4 |
| Family history of premature CV disease b , c (%) | 26.9 | 5.4 | 13.2 | 24.7 | 66.7 | 29.9 |
| Current smoker b (%) | 11.6 | 2.3 | 4.5 | 9.4 | 29.0 | 13.3 |
| Hypertension b (%) | 69.5 | 8.9 | 49.3 | 72.2 | 89.2 | 78.6 |
| Ischaemic heart disease b (%) | 34.0 | 0 | 0 | 0 | 0 | 55.1 |
| Diabetes mellitus b (%) | 32.9 | 1.9 | 10.9 | 11.4 | 0 | 48.2 |
| Cerebrovascular disease b (%) | 7.5 | 0 | 0 | 0 | 0 | 12.2 |
| Peripheral artery disease b (%) | 13.4 | 0 | 0 | 0 | 0 | 21.7 |
| Metabolic syndrome b (%) | 59.6 | 25.3 | 42.8 | 54.1 | 68.4 | 66.7 |
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