Focus on Lifestyle to Reduce Cardiovascular Risk
Pharmacotherapeutic intervention, in particular targeting elevated cholesterol, has undoubtedly been successful in reducing the mortality and morbidity of patients with cardiovascular disease.1 However, these gains have now been largely overtaken by escalating rates of obesity and cardiometabolic disease, driven by the adoption of energy-dense diets and a sedentary lifestyle. The INTERHEART study, a global case-control study, previously showed that a Western high-fat diet, a driver for the development of hypercholesterolaemia, is associated with increased coronary risk.2 As seen in China, an increasingly Westernised diet and associated increase in total cholesterol have contributed to marked increases in coronary heart disease mortality (by 50 % in men and by 27 % in women) despite improved access to better treatment.3
Clearly, improved lifestyle is a key component of modern preventive cardiology, as recognised by the recently published European Atherosclerosis Society (EAS)/European Society of Cardiology (ESC) joint guidelines for management of dyslipidaemia.4 These new guidelines also place emphasis on nutritional approaches, either alone or complementary to pharmacotherapy, in managing hypercholesterolaemia to reduce cardiovascular risk. As highlighted by Eric Bruckert, Director of the Endocrinology-Metabolism and Prevention of Cardiovascular Disease Department at the Pitié-Salpêtrière Hospital in Paris, in his presentation, adherence to a healthy diet from an early age has been shown to translate to a reduction in the risk of coronary heart disease and diabetes.5 However, the biggest challenge in implementing lifestyle advice is sustaining change in the long term.
Are there Practical Tools that can Help in Adherence to Dietary Changes?
Bruckert reviewed data showing that preventive programmes for managing cardiovascular risk factors that include both education and a self-monitoring component, such as measuring blood glucose or blood pressure, were beneficial in helping patients sustain improvements in lifestyle.6,7 Furthermore, the use of a pedometer8 not only increased physical activity but also improved other cardiovascular risk factors, suggesting that simple practical tools might help in promoting a lifestyle change.
However, it is recognised that sustained improvement in nutritional behaviour, of particular relevance in the management of dyslipidaemic patients, is more difficult to achieve. Key components required for implementing dietary advice should include:
- assessment of dietary intake;
- recommendations for lifestyle changes;
- practical advice on how to implement dietary changes; and
- self-monitoring.
Monitoring dietary intake is crucial to this process. Bruckert emphasised that the dietary intake questionnaire should be specific for the target population, be easy to conduct or to perform as a self-assessment, and provide an accurate and reliable measure of food intake.9 However, in practice, an appropriate validated tool that would allow patients to monitor their dietary intake has been lacking.
This issue has been addressed by Bruckert and colleagues. He presented data relating to the validation of a new food frequency questionnaire, the Nutritional Lifestyle questionnaire, which has been specifically adapted for the assessment of dyslipidaemic patients.10 This questionnaire was designed to evaluate adherence to key dietary recommendations for a desirable lipid profile as defined by Graham et al.11 and Lichtenstein et al.12 The questionnaire was selected for the assessment of nutritional lifestyle behaviour in the Reduce cholesterol involving patient endorsement (RECIPE) study.
The Reduce Cholesterol Involving Patient Endorsement Study
Does Phytosterol-supplementation have a Role in Improving Adherence to Lifestyle Changes?
The RECIPE study is an international, prospective observational survey being conducted in general practice in Spain and France. It is planned to involve other countries in Europe in the near future. The aim of the study is to assess the role of functional foods, specifically phytosterol-supplemented yogurt (PEY, Danacol®, Danone) in improving nutritional behaviour and lifestyle in patients with moderate hypercholesterolaemia as defined by current guidelines,4 either treated with lipid-lowering therapy or untreated.
Patients were to be considered for the study provided that their general practitioner had decided to recommend daily intake of PEY, in addition to comprehensive lifestyle modification for the management of hypercholesterolaemia. Patients already receiving foods supplemented with stanols or phytosterols, patients in whom a change in therapy was planned and pregnant women were to be excluded. Each general practitioner was to include five consecutive patients. The primary outcome of the study was a change in the Nutritional Lifestyle score.10 The clinician conducted the questionnaire at baseline and at four months, and the patient carried out a self-assessment using the questionnaire at one month, with responses scored and evaluated as summarised in Table 1.
Lluis Masana, Professor of Medicine and Head of the Vascular Medicine and Metabolism Unit, Institut d'Investigació Sanitària Pere Virgili, University Hospital Sant Joan, Reus, presented the results from Spain.13 In total, 1,048 patients (median age 56 years, 57 % female, 86 % from an urban setting) were included by 201 general practitioners. The most frequent reasons cited by clinicians when recommending PEY were to avoid the use of lipid-lowering therapy (40 % of clinicians) – notably in patients with borderline dyslipidaemia (33 %) – or as part of systematic approach to the management of hypercholesterolaemia (39 %).
The predominantly primary prevention patient population had a mean low-density lipoprotein (LDL) cholesterol of 4.1 (± standard deviation [SD] 0.8 mmol/l), with about half of the patients receiving lipid-modifying therapy (a statin in most cases). Not surprisingly, there was a high prevalence of cardiovascular risk factors; 25 % of patients were overweight/obese, 47 % had central obesity, 37 % had hypertension, 21 % were smokers and 13 % had type 2 diabetes (see Table 2). Only 25 % of patients reported that they exercised regularly.
Diet composition, as assessed by the Nutritional Lifestyle score, significantly improved over four months. The overall mean score (in points) decreased by 31 % at one month, and this effect was sustained at four months (13.5 ± 5.0 at baseline, 9.5 ± 4.0 at one month and 8.2 ± 3.9 at four months). The proportion of patients with a diet that improved their cholesterol increased from 28 % at baseline to 75 % at four months, whereas the proportion of patients whose diet was not optimal for their cholesterol decreased from 63 % at baseline to 25 % at four months (see Figure 1).
Daily intake of PEY was associated with significant decreases in LDL cholesterol (by 13.2 %), total cholesterol (by 11.1 %) and triglycerides (by 5.2 %), and with an increase in high-density lipoprotein (HDL) cholesterol (by 7.2 %) (all p<0.0001), with similar responses evident in patients receiving lipid-modifying therapy (see Table 3). Masana emphasised that, in statin-treated patients, the magnitude of the incremental decrease in LDL cholesterol with daily PEY intake was similar to the effect of doubling the dose of statin,14 but without the potential for adverse effects associated with high-dose statin therapy.
Of key interest, the regular intake of PEY appeared to act as a driver for improving other cardiovascular risk factors, including reduction in body mass index (BMI) and waist circumference (see Figure 2) and increased physical activity (see Figure 3). These benefits, although small, were of clinical relevance and evident in both treated and treatment-naive patients. Masana concluded that these findings from the RECIPE study indicate that the daily intake of PEY, as part of a comprehensive lifestyle modification programme, not only improved the lipid profile, but also acted as a tool to help hypercholesterolaemic patients sustain improvements in lifestyle likely to impact positively on their cardiovascular risk.
Implications for Improving Lifetime Cardiovascular Risk at the Population Level
The findings of the RECIPE study are relevant when considered in the context of lifetime cardiovascular risk, as discussed by John Deanfield, Professor of Cardiology and Head of Cardiovascular Prevention, University College London. In his presentation, he emphasised the need for clinicians to consider the evolution of atherosclerosis in preventive approaches. The later phase of atherosclerosis associated with clinical events is the usual target for cardiovascular disease prevention. However, there is clear evidence of the emergence of atherosclerotic disease early in life. Using intravascular ultrasonography, researchers showed that nearly one in five adolescents (<20 years of age) had evidence of atheroma and this proportion increased to 85 % during middle-age (≥50 years of age).15 These data clearly underline the need for an early proactive lifestyle approach, consistent with recent European guidelines.4 Optimal risk factor management would be expected to translate to a reduction in the lifetime risk of cardiovascular events.
Deanfield recognised that adherence to a healthy lifestyle is a major obstacle to the success of such approaches. He cited evidence from the Atherosclerosis risk in communities (ARIC) study,16 including 12,744 subjects initially free of cardiovascular disease, which showed that only 0.1 % (12 subjects) maintained an ideal healthy lifestyle in the long term. While increased body weight and central obesity were associated with elevated levels of cardiovascular risk factors, only a small decrease in weight (by 4.5 kg or 10 pounds) was needed to improve cholesterol, with the potential for translating to a substantial benefit in terms of lifetime cardiovascular risk.16 Deanfield also discussed evidence showing that improvement in nutritional behaviour – for example, by adoption of the Mediterranean diet – led to small but significant improvements in several cardiovascular risk factors, including weight, blood glucose and systolic blood pressure.17 Considering these data together, he concluded that targeting lifestyle intervention at a younger age is likely to result in greater health gains.
This premise underlies the concept of lifetime cardiovascular risk, which is being used as a basis for clinical decision-making for preventive strategies in the updated Joint British Societies’ guidelines on the prevention of cardiovascular disease (JBS3) due to be published soon. To date, guidelines have focused on the estimation of 10-year risk of cardiovascular events as a guide to clinical decision-making; however, as discussed by Deanfield, this approach largely disenfranchises women and younger individuals who may be at low absolute but high relative cardiovascular risk. Improvements in lifestyle, complementary to drug therapy, lead to small improvements in cardiovascular risk factors such as lipids, BMI and waist circumference, as observed in the RECIPE study, and thereby offer the potential for reduced lifetime cardiovascular risk. Such an approach is likely to have public health benefits at a societal level.
Physiology of Taste – Does Lipid Sensing Have a Role in the Development of Obesity?
Finally, Philippe Besnard, Professor and Head of the Nutrition Physiology and Toxicology Research Unit at the French National Institute of Health and Medical Research, University of Bourgogne, Dijon, presented interesting experimental data suggesting a role for lipid sensing in the development of obesity.
Humans and rodents are able to detect low concentrations of fatty acids of variable length.18,19 Besnard gave an overview of the accumulating evidence that the multifunctional receptor-like membrane protein CD36 (also called fatty acid transporter), a member of the scavenger receptor B1 family of receptors, may be involved in lipid sensing.20 This protein is located on the gustatory epithelia of the tongue in rodents and humans, notably the circumvallate papillae,21 which is particularly suitable because taste receptor cells here are potentially exposed to high levels of long-chain fatty acids. There is an increasing body of evidence that suggests that lingual CD36 may be a lipid sensor involved in the oro-sensory detection of dietary lipids and the cephalic phase of digestion in the mouse, although whether this is also the case in humans is not yet clear.
It has been suggested that the perception of dietary lipids might be implicated in the development of obesity. Obese patients have been shown to exhibit a higher preference for fat than lean subjects, possibly due to the rewarding effects of fatty foods and/or linked with the inappropriate perception of fatty foods.22 Besnard gave an overview of the evidence from a recent study in healthy individuals that showed that hypersensitivity to fatty acids was associated with lower energy and fat intakes and, in turn, lower BMI.23 However, whether changes in fatty acid sensitivity are also implicated in nutritional behaviour in overweight individuals remains the subject of further investigation.
Concluding the symposium, John Chapman, EAS President, commented that, while lifestyle remains the cornerstone of managing hypercholesterolaemia, motivation and adherence can be major obstacles to change. The findings from the RECIPE study, conducted in a real-life clinical setting, show that the daily intake of PEY not only improved lipids but also appeared to be a driver for change, helping to empower patients to sustain a healthier lifestyle, with potential for long-term benefits regarding their cardiovascular risk.