[How I treat ... dyslipidemia according to the cardiovascular risk profile]. / Comment je traite ... une dyslipidémie en fonction du profil de risque cardiovasculaire.

The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of new items. Here we demonstrate their application in several different clinical examples. We focus on the 4 items most pertinent for medical practice: 1) the stratification of risk of cardiovascular disease into 4 categories ('very high', 'high', 'moderate' and 'low risk'), involving--for primary prevention cases--the use of the SCORE table, which has been calibrated for Belgium and where the risk can be adjusted according to HDL cholesterol and the presence of other risk factors; 2) the choice of more stringent therapeutic targets for LDL cholesterol (< 70 mg/dl for 'very high' risk patients, 100 mg/dl for 'high' risk patients and 115 mg/dl for patients at 'moderate' risk); 3) the choice of other therapeutic targets (non-HDL cholesterol and apolipoprotein B levels) for patients at 'very high' or 'high' risk with combined dyslipidaemia; and 4) follow-up of lipid parameters and muscular and hepatic enzymatic profiles.

[New European guidelines for the management of dyslipidaemia in cardiovascular prevention]. / Les nouvelles recommandations Européennes pour le traitement des dyslipidémies en prévention cardiovasculaire.

The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of updated items. In this paper, we summarize 4 of these changes that we consider to be the most pertinent. Firstly, cardiovascular risk is now stratified according to 4 (previously 2) categories: "very high risk" (patients with cardiovascular disease, patients with diabetes > 40 years old who have at least one other risk factor, patients with kidney failure, or patients in primary prevention with a SCORE value > or = 10%); "high risk" (patients in primary prevention with a SCORE value > or = 5% and < 10% or patients with a particularly serious risk factor such as familial hypercholesterolaemia or patients with diabetes < 40 years old without any other risk factor); "moderate risk" (primary prevention with SCORE > or = 1% and < 5%); and "low risk" (primary prevention with SCORE < 1%). The SCORE value for patients in primary prevention is estimated using the SCORE table (calibrated for Belgium). Risk in this table may now be corrected according to HDL cholesterol level. Secondly, the therapeutic targets for each category are now more stringent: LDL cholesterol < 70 mg/dl (or reduced by at least 50%) if the risk is "very high"; < 100 mg/dl if the risk is "high"; and < 115 mg/dl if the risk is "moderate". Thirdly, for patients at "high" or "very high" risk, particularly in patients with combined dyslipidaemia, two further therapeutic targets should be considered: non-HDL cholesterol and apolipoprotein B levels. Fourthly, the follow-up of efficacy (lipid profile) and tolerance (hepatic and muscular enzymes) is described in more details so as to harmonize case management in clinical practice.

Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization.

UNLABELLED: Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations. 1. Screening for HeFH should be performed only in children older than 2 years when HeFH has been identified or is suspected (based on a genetic test or clinical criteria) in one parent.2. The diagnostic procedure includes, as a first step, the establishment of a clear diagnosis of HeFH in one of the parents. If this precondition is satisfied, a low-density-lipoprotein cholesterol (LDL-C) levelabove 3.5 mmol/L (135 mg/dL) in the suspected child is predictive for differentiating affected from non-affected children. 3. A low saturated fat and low cholesterol diet should be started after 2 years, under the supervision of a dietician or nutritionist.4. The pharmacological treatment, using statins as first line drugs, should usually be started after 10 years if LDL-C levels remain above 5 mmol/L (190 mg/dL), or above 4 mmol/L (160 mg/dL) in the presence of a causative mutation, a family history of early cardiovascular disease or severe risk factors. The objective is to reduce LDL-C by at least 30% between 10 and 14 years and, thereafter, to reach LDL-C levels of less than 3.4 mmol/L (130 mg/dL). CONCLUSION: The aim of this consensus statement is to achieve more consistent management in the identification and treatment of children with HeFH in Belgium.

Validation of the IMMIDIET food frequency questionnaire in an adult Belgian population: a report from the Belgian case-control study on bladder cancer risk.

We evaluated the performance of the IMMIDIET food frequency questionnaire (FFQ) used to collect dietary data for the Belgian case-control study on bladder cancer. Thirty-seven men and women aged 50 years and older were recruited from the University Hospital in Leuven, Belgium. Participants completed the IMMIDIET FFQ, a 7-day diet diary and a 24-hour diet recall. Median intakes and inter-quartile ranges were calculated for 27 foods and nutrients from each dietary assessment method. All dietary factors were log-transformed and adjusted for energy using the nutrient density method. Pearson correlation coefficients were used to compare the different dietary assessment methods. Bland-Altman plots were also used to assess levels of agreement between the dietary methods. Energy, fruit and vegetable intake estimates were higher from the IMMIDIET FFQ compared with the two reference methods.The highest deattenuated correlations between the FFQ and 7-day diary were meat (0.58), bread (0.44), fruit (0.38) and fish (0.38). The highest deattenuated correlations between the FFQ and 24-hour recall were for fruit (0.72), fat (0.48), alcohol (0.44), cholesterol (0.42), monounsaturated fatty acid (0.42) and polyunsaturated fatty acid (0.41). Generally, correlation was lower for the micro-nutrients except for phosphorus (0.42), vitamin C (0.41) and calcium (0.40). The IMMIDIET FFQ is an appropriate instrument to measure usual dietary intake for the Belgian case-control study on bladder cancer risk. Further investigation of nutritional assessment methods is necessary.

Mortality of young patients with diabetes in Kinshasa, DR Congo.

AIMS: As data on mortality of young patients with diabetes is not available in the Democratic Republic of Congo (DRC), we studied mortality rates, the influence of some determinants and causes of death. METHODS: A retrospective review of standardized medical records of all patients with diabetes aged

Niacin, an old drug with new perspectives for the management of dyslipidaemia.

Niacin has been used for decades to treat dyslipidaemic disorders. Niacin is the most effective agent currently available for increasing levels of high-density lipoprotein. Moreover, significant improvements in cardiovascular outcomes in niacin treated patients have been demonstrated. However, tolerability concerns, particularly flushing, have limited its use in the past. Therefore, ER niacin, a prolonged-release formulation of niacin, has been developed with similar efficacy but a superior tolerability profile compared to the immediate-release formulations. Recent insights on niacin mechanisms of action have led to the development of a new agent called laropiprant. Laropiprant selectively blocks the binding of prostaglandin D2 to its receptor (DP1) in dermal capillaries, which mediates niacin-induced vasodilation. When co-administered with ER niacin, a marked reduction in ER niacin induced flushing is seen.The clinical use of niacin and the novel flush-reducing co-medication, will be discussed.

Determination de la prevalence du diabete gestationnel et des facteurs associes a Kinshasa

Objectif. Determiner la prevalence du diabete gestationnel (DG) et rechercher ses facteurs associes a Kinshasa. Materiel et Methodes. Une etude multicentrique transversale a ete realisee de juin a decembre 2005 dans 10 formations medicales de Kinshasa selectionnees de maniere randomisee. Elle a porte sur 861 gestantes tout venants a partir de 24 semaines de grossesse. Le diagnostic du DG a ete pose grace a des glycemies obtenues a l'aide d_fun glucometre a reflectance lors des epreuves de depistage. Ce dernier a ete effectue en 2 temps :d'abord le test de O'Sullivan apres charge orale de 50g de glucose ; une semaine plus tard; les gestantes ayant eu une glycemie . 140 mg/dL et 200 mg/dL ont subi le test complet apres charge glucosee de 100g. Les tests du Chi-carre et la regression logistique ont ete utilises pour rechercher les determinants du DG. Resultats. La prevalence du DG a ete respectivement de 3;9et 5;2selon les tests de O'Sullivan et de l'epreuve d'hyperglycemie provoquee orale classique. Les facteurs de risque associes au DG dans cette etude on ete lobesite e (OR 5;4; IC95: 1;66 . 16;9); l'age . 35 ans (OR 2;56; IC95: 1;24 . 5;25); la parite (OR 2;84 ; IC95: 1;42 . 5;67) et l'antecedent de macrosomie (OR 2;88 ; IC95: 1;17 . 6;88). Conclusion. Le taux de prevalence de 5;2 montre que le DG constitue un probleme de sante publique dans la ville de Kinshasa. Le test de O'Sullivan est une alternative valable pour sa detection. L'obesite constitue le determinant majeur du DG et plus particulierement apres 35 ans

Estimation des besoins energetiques chez la gestante noire congolaise de Kinshasa

Objectif : Determiner les besoins energetiques gravidiques dans une population obstetricale noire de Kinshasa. Echantillon et methodes : une etude longitudinale par impedance bioelectrique de la composition corporelle et du metabolisme basal a differents ages gestationnels a ete menee chez 76 gestantes. Les besoins energetiques ont ete estimes a partir du gain gravidique en graisse et en proteine; du pied neonatal et des modifications physico-chimiques induites par une grossesse normale. Resultats : les resultats les plus caracteristiques sont : un gain ponderal calcule de 10 000 g en graisse de 2 333 g; inferieur aux 3 300 g recommandes ; un cout energetique de depot de 27362 kcal ; et un cout energetique total de la grossesse de 70 029 kcal. Conclusion : Le cout energetique gravidique total etant de 70 029; soit presque identique a la recommandation de Prentice et coll. (72 000 kcal); la faiblesse du depot graisseux pre-gravidique notable; susceptible de servir de point de depart a un ajustement metabolique pregravidique

[A Longitudinal study of body composition and basal metabolic rate during pregnancy in a black population of Kinshasa, Democratic Republic of Congo (RDC)]. / Evolution de la composition corporelle et du métabolisme basal au cours de la grossesse chez la noire congolaise de Kinshasa, République démocratique du Congo (RDC).

OBJECTIVE: A longitudinal study of body composition and basal metabolic rate during pregnancy in a black population of Kinshasa. MATERIALS AND METHODS: Body composition and basal metabolic rate were determined by bioimpedance, and energy intake was evaluated using the 24 h recall method at 20, 34 and > 37 weeks of gestation in 76 black, Congolese women. The subjects had to be healthy, and to deliver term, singleton infants after a normal pregnancy. RESULTS: At 20 weeks of pregnancy, the 76 women, aged 28.5+/-6.4 years, had a body weight of 61.1+/-7.7 kg, a body mass index of 23.0+/-3.8 kg/m(2), a fat mass of 36.6+/-6.8% and a basal metabolic rate of 1399+/-84 kcal/24 h. Subsequently, increases in body weight (+6.5 kg), fat-free mass (+ 5.1 kg), body water (+4.4 l) and basal metabolic rate (+297 kcal/24 h) (P < 0.0001) were observed. The increase in fat mass (+1.4 kg) was less pronounced. Energy intake was stable. CONCLUSION: Changes in body composition during pregnancy in Congolese black women are comparable to those reported in other populations. Pre- and per-gravidic fat mass is higher in congolese women than in Caucasian women.

Obesity in diabetic patients in Kinshasa, Democratic Republic of Congo.

OBJECTIVE: To assess the distribution of Mass Index (BMI) and the prevalence of obesity at the time of diagnosing diabetes in the primary health care network in Kinshasa, Democratic Republic of Congo (DRC), from 1993 to 1999. METHODOLOGY: A total of 4967 patients with diabetes were classified according to BMI, age at diagnosis (< 30 years versus > or = 30 years), sex and subsequent treatment (insulin treated versus non-insulin treated). WHO criteria were used to define diabetes and obesity. RESULTS: One diabetic patient in 4 was underweight (26.4%). The prevalence of obesity was 8.1%. Undernutrition was more prevalent in male patients aged < 30 years at diagnosis and, in contrast, obesity was more prevalent in patients aged > or = 30 years at diagnosis, especially among women. CONCLUSION: Undernutrition is highly prevalent at the time of diagnosis in young diabetic patients in Kinshasa. The overall prevalence of obesity at diagnosis is relatively low, except in women diagnosed at > or = 30 years of age. Prospective studies are needed in the Democratic Republic of Congo to characterize secular trends of undernutrition and obesity in order to improve preventive and management strategies.

Predictors of 6-minute walk test results in lean, obese and morbidly obese women.

The aim of this study was first, to assess the presence of medical conditions that might interfere with walking; second, to assess the differences in walking capacity, perceived exertion and physical complaints between lean, obese and morbidly obese women; and third, to identify anthropometric, physical fitness and physical activity variables that contribute to the variability in the distance achieved during a 6-minute walk test in lean and obese women. A total of 85 overweight and obese females (18-65 years, body mass index (BMI) > or = 27.5 kg m(-2)), 133 morbidly obese females (BMI > or = 35 kg m-2) and 82 age-matched sedentary lean female volunteers (BMI < or = 26 kg m(-2)) were recruited. Patients suffering from severe musculoskeletal and cardiopulmonary disease were excluded from the study. Prior to the test, conditions that might interfere with walking and hours of TV watching were asked for. Physical activity pattern was assessed using the Baecke questionnaire. Weight, height, body composition (bioelectrical impedance method), isokinetic concentric quadriceps strength (Cybex) and peak oxygen uptake (peakVO2_bicycle ergometer) were measured. A 6-minute walk test was performed and heart rate, walking distance, Borg rating scale of perceived exertion (RPE) and physical complaints at the end of the test were recorded. In obese and particularly in morbidly obese women suffering from skin friction, urinary stress incontinence, varicose veins, foot static problems and pain, wearing insoles, suffering from knee pain, low back pain or hip arthritis were significantly more prevalent than in lean women (P < 0.05). Morbidly obese women (BMI > 35 kg m(-2)N = 133) walked significantly slower (5.4 km h(-1)) than obese (5.9 km h(-1)) and lean women (7.2 km h(-1), P < 0.05), were more exerted (RPE 13.3, 12.8 and 12.4, respectively, P < 0.05) and complained more frequently of dyspnea (9.1%, 4.7% and 0% resp., P < 0.05) and musculoskeletal pain (34.9%, 17.7% and 11.4% resp., P < 0.05) at the end of the walk. In a multiple regression analysis, 75% of the variance in walking distance could be explained by BMI, peakVO2, quadriceps muscle strength age, and hours TV watching or sports participation. These data suggest that in contrast with lean women, walking ability of obese women is hampered not only by overweight, reduced aerobic capacity and a sedentary life style, but also by perceived discomfort and pain. Advice or programs aimed at increasing walking for exercise also need to address the conditions that interfere with walking, as well as perceived symptoms and walking difficulties in order to improve participation and compliance.

Health-related quality of life in physically active and sedentary obese women.

The aim was to assess dimensions of health-related quality of life (HRQL) in women attending an obesity clinic, and to rate differences in HRQL in those with the highest and lowest levels of physical activity (PA). The sample included 113 sedentary and 101 physically active subjects from a total sample of 375 overweight women 16-65 years, with a body mass index (BMI) > or =27.5 kg/m(2) consulting at an outpatient Endocrinology Clinic, and 82 lean female volunteers who served as a reference. Weight, height, body composition, PA, physical medical conditions, depression, body image, cognitive-behavioral conceptualization of obesity, eating behavior, functional status, walking ability, exercise capacity, social functioning, and general health and perceived quality of life were assessed cross-sectionally. The prevalence of medical conditions and depression was not statistically different (P < 0.05) in sedentary and active women. In sedentary obese women, body attitude, walking ability, and aerobic fitness were poorer; the number of people to turn to for social support was smaller; physical attributions about the basis of the subjects obesity were less pronounced; and eating was more the consequence of external triggers or diffuse emotions than in physically active obese women (P < 0.05). The findings indicate that a higher level of PA in an obese female clinical population was positively associated with diverse dimensions of HRQL. However, it was not possible to determine if these favorable aspects of HRQL are the cause or the consequence of a higher PA level.

The role of early hemodynamic impairment and disease duration on diabetic cardiomyopathy and hypertension in central Africans with atherosclerosis.

Diabetes mellitus (DM) is strongly associated with cardiomyopathy and hypertension. This study focuses on early hemodynamic impairment and DM exposure time amplified by atherosclerosis before the onset of associated cardiomyopathy and hypertension in central Africans. Prospectively, demographic, hemodynamic, lipid, anthropometric, and urinary data of 48 atheromatous diabetics, 39 uncomplicated diabetics, and 27 normal subjects before incidence of cardiomyopathy, hypertension, stroke, and peripheral vascular disease (PVD) were analysed. Age, waist-hip ratio (WHR), DM duration, blood pressures (BPs), pulse pressure (PP), mean arterial pressure (MAP), lipidic profile, and microalbuminuria were more elevated in atheromatous diabetics than in uncomplicated diabetes and normal subjects. PP, MAP, BP of atheromatous diabetics were significantly (P<.01) correlated with age, DM duration, and microalbuminuria, but stroke volume was negatively (P<.001) correlated with diastolic blood pressure (DBP) and microalbuminuria. The evolution of atheromatous diabetes was characterized by the onset of the highest rates of hypertension (86.2%), cardiomyopathy and congestive failure (69%), stroke (46%), and PVD (42%). Atheromatous diabetes of central Africans is associated with early and age-induced significant changes of PP, BP, the highest rates of hypertension, cardiomyopathy, stroke, and PVD. Impaired left ventricular function, as stroke volume decreases with increasing DBP, C-peptide, and microalbuminuria, precedes cardiomyopathy and congestive failure in African diabetics.

The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study.

OBJECTIVE: Assessment of the effects of orlistat 120 mg three times daily vs placebo on weight loss and serum lipids in obese hypercholesterolemic patients. DESIGN: A 24 week multicentre, double-blind, randomized, placebo-controlled trial. After a 2-week single-blind run-in period (placebo+diet (-600 kcal/day; < or =30% of calories as fat)), 294 patients were submitted to the hypocaloric diet and randomly assigned to either orlistat 120 mg or placebo three times daily. Patients who completed the double-blind study (n=255) were eligible for participation in a subsequent 24 week open-label orlistat extension phase. SUBJECTS: Patients with body mass index (BMI) 27-40 kg/m2 and hypercholesterolemia (low-density-lipoprotein cholesterol, LDL-C, 4.1-6.7 mmol/l). MEASUREMENTS: Efficacy assessments included weight loss, lipid levels, other cardiovascular risk factors and anthropometric parameters. Safety assessments. RESULTS: Weight loss during run-in was similar in both groups. After randomization, orlistat-treated patients lost significantly more weight than placebo recipients: mean percentage weight loss from start of run-in to week 24 was-6.8% in the orlistat group and -3.8% in the placebo group (P<0.001). Moreover, more patients in the orlistat group than in the placebo group achieved clinically meaningful weight loss of > or =5% (64 vs 39%) or > or =10% (23 vs 13%) at week 24. Treatment with orlistat was associated with significantly greater changes in total cholesterol (-11.9% vs -4.0%; P<0.001) and LDL-C (-17.6 vs -7.6%; P<0.001). For any category of weight loss during the double-blind treatment period, change in LDL-C was more pronounced in orlistat-treated patients than in placebo recipients, indicating that orlistat had a direct cholesterol-lowering effect that was independent of weight reduction (P<0.001). Adjunction of orlistat during the extension phase in patients who initially received placebo induced a further decrease in weight, total cholesterol and LDL-C. Orlistat was generally well tolerated with a safety profile comparable to placebo, with the exception of a higher incidence of gastrointestinal events (> or =1 event in 64 vs 38% of patients). CONCLUSION: Orlistat as an adjunct to dietary intervention promotes weight loss and reduces LDL-C beyond the effect of weight loss in overweight or obese patients with concomitant hypercholesterolemia.

Exercise capacity in lean versus obese women.

The aim of this study was to assess the nature and magnitude of the differences in submaximal and maximal exercise capacity parameters between lean and obese women. A total of 225 healthy obese women 18-65 years (BMI> or=30 kg/m(2)) and 81 non-athletic lean women (BMI< or=26 kg/m(2)) were selected. Anthropometric measurements (weight and height), body composition assessment (bioelectrical impedance method) and a maximal exercise capacity test on a bicycle ergometer were performed. Oxygen uptake (VO(2)), carbon dioxide production (VCO(2)), expired ventilation (VE), respiratory quotient (RQ), breathing efficiency (VE/VO(2)), mechanical efficiency (ME) and anaerobic threshold (AT) were calculated. At a submaximal intensity load of 70 W, VO(2) (l/min) was larger in the obese women and was already 78% of their peak VO(2), whereas in the non-obese it was only 69% (P=0.0001). VE (l/min) was larger, VE/VO(2) did not differ and ME was lower in obese compared to the lean women. AT occurred at the same percentage of peak VO(2) in both lean and obese women. At peak effort, achieved load, terminal VO(2) (l min(-1) kg(-1)), VE, heart rate, RQ respiratory exchange ratio and perceived exertion were lower in obese subjects compared to the non-obese. Obese subjects mentioned significantly more musculoskeletal pain as a reason to end the test, whereas in lean subjects it was leg fatigue. Lean women recovered better as after 2 min they were already at 35% of the peak VO(2), whereas in the obese women it was 47% (P=0.0001). Our results confirm that exercise capacity is decreased in obesity, both at submaximal and peak intensity, and during recovery. Moreover, at peak effort musculoskeletal pain was an important reason to end the test and not true leg fatigue. These findings are important when designing exercise programs for obese subjects.

The effect of atorvastatin on postprandial lipaemia in overweight or obese women homozygous for apo E3.

OBJECTIVE: To determine the effect of atorvastatin on postprandial lipaemia in overweight or obese women with the apoprotein (apo) E3/E3 genotype. DESIGN: Double-blind randomised, placebo-controlled 8-week single-centre study. SUBJECTS: Twenty-two healthy women, homozygous for apo E3 with a BMI ranging from 27.6 to 41.1 kg/m2 and normal or moderately elevated fasting triglycerides (53-184 mg/dl). TREATMENT: After a 4-week isocaloric single-blind, placebo lead-in period, subjects were randomly assigned to receive either placebo (n = 7) or atorvastatin 20 mg once daily in the evening (n = 15) for 4 weeks. RESULTS: Atorvastatin significantly reduces fasting total cholesterol, LDL-cholesterol and postprandial triglycerides in obese women, homozygous for apo E3 with normal or near-normal fasting triglyceride levels. No significant effect on fasting triglycerides was observed. CONCLUSION: Atorvastatin decreases postprandial hyperlipidaemia, an independent cardiovascular risk factor, in normolipidaemic obese women. This effect of atorvastatin may, therefore, represent a cardioprotective mechanism.

The efficacy of atorvastatin in treating patients with hypercholesterolaemia to target LDL-cholesterol goals: the LIPI-GOAL trial.

OBJECTIVE: LIPI-GOAL is a multicentre, open-label, non-comparative treat-to-target study, conducted from March 1998 to May 1999, that assessed the percentage of patients reaching 1992 European Atherosclerosis Society (EAS) low-density lipoprotein cholesterol (LDL-C) targets with atorvastatin 10-80 mg/day in subjects with hypercholesterolaemia, defined as LDL-C > 160 mg/dl after a 12-week step I diet. METHODS AND RESULTS: Patients were treated towards the following LDL-C goals: < 135 mg/dl in patients with atherosclerotic disease present and/or coronary heart disease (CHD) risk >40%/10 years, or LDL-C < 155 mg/dl in all others. All subjects started treatment with atorvastatin 10 mg/day for 6 weeks. The dose was doubled every 6 weeks, to 20, 40, or 80 mg/day at weeks 12, 18, and 24, respectively, if targets were not reached. Of 587 patients screened for participation, 473 were enrolled and 419 (59% male; mean age 61 years) were available for efficacy evaluation. Fifty-five percent had atherosclerotic disease and/or CHD risk >40%/10 years. Dose titration was not needed in 303 patients (72%) who reached LDL-C target with atorvastatin 10 mg/day. Among 116 patients who were subsequently treated with higher atorvastatin dosages, 47 reached LDL-C target with 20 mg/day, 15 with 40 mg/day, and 6 with 80 mg/day. Therefore, 88.5% of subjects reached LDL-C goal in an intention-to-treat analysis. In general, atorvastatin was well tolerated. CONCLUSIONS: Most patients at high risk for CHD reached LDL-C goals with atorvastatin 10-80 mg/day. Seventy-two % of patients reached target with atorvastatin 10 mg/day, which may simplify clinical management and should encourage better adherence to recommendations.