Risk factor management: a practice guide

Guidelines and Expert Consensus Documents evaluate currently available scientific evidence with the aim to assist physicians in selecting the best management strategies. The Guidelines on the Prevention of Cardiovascular Disease in Clinical Practice edited by the 4th Joint European Societies Taskforce are no substitutes for textbooks. The document, of which a short summary is given in this paper, should guide physicians to make decisions but the ultimate judgment regarding the care of an individual patient must be made by the physician in charge of his/her care [1]. According to the taskforce, the rationale for the prevention of cardiovascular disease (CVD) is based on the following: CVD is the major cause of premature death and disability in Europe. It causes more than 4.35 million deaths; 43% of all deaths in men and for 55% in women of all ages [2]. The underlying atherosclerosis develops insidiously over many years and is usually advanced and difficult to reverse by the time that symptoms occur. The occurrence of CVD relates strongly to modifiable lifestyle and physiological factors. Risk factor modifications have been unequivocally shown to reduce mortality and morbidity, particularly in high-risk patients. CVD mortality rates vary with age, sex, socioeconomic status, ethnicity and geographical region. There are marked socioeconomic gradients in coronary heart disease (CHD) morbidity and mortality within European countries. These differences are partially explained by socioeconomic differences in conventional risk factors, such as smoking, blood pressure (BP), blood cholesterol and glucose [3]. The decreases in risk factors such as smoking, serum cholesterol and BP explains more than 50–75% of the decline of CHD mortality in several countries over the past decades [4, 5]. Yet, the European Action on Secondary And Primary Prevention by Intervention to Reduce Events (EUROASPIRE) surveys showed that there remains an unsatisfactory control of risk factors in patients with established CVD, especially of obesity, smoking and BP despite issued guidelines [6–8]. The WHO report on prevention of coronary heart disease distinguished three components for prevention: a population, a high-risk and a secondary prevention strategy [9]. The population strategy aims at shifting the distribution of risk factors towards more favourable levels through actions directed to change the environment and lifestyle of individuals, without the need to medically examine them, in order to reduce the incidence of disease by preventing or delaying the occurrence of CVD. The high-risk primary prevention strategy deals with healthy persons with high absolute risks of future disease. The secondary prevention strategy deals with patients with established cardiovascular organ damage or disease. Cardiac rehabilitation and prevention programmes including exercise training have proven to be effective in improving processes of care, readmissions to hospital, functional status and overall mortality. There is no evidence that mass screening for detection of early stages of CVD is cost-effective [10]. Instead, in the primary care setting, family doctors may play an important role in identifying and managing people at risk. The objectives of cardiovascular prevention are to reduce mortality and morbidity in those at high absolute risk and to assist those at low absolute risk to maintain this state. As individuals at highest risk gain most from preventive effort, priorities are as follows: Patients with established CVD, whether of the coronary, peripheral, cerebral vessels or of the aorta. Asymptomatic individuals who are at high risk of symptomatic CVD because of: Multiple risk factors resulting in a markedly raised total CVD risk. Markedly raised levels of single risk factors – cholesterol ≥ 8 mmol/l, low density lipoprotein (LDL) cholesterol ≥ 6 mmol/l, BP ≥ 180/110 mmHg. Diabetes type 2 and diabetes type 1 with microalbuminuria. First-degree relatives of persons with early-onset atherosclerotic CVD (men before the age of 55 years, women before 65 years of age). Characteristics of a heart-healthy population Characteristics of a heart-healthy population Target values for patients with established CVD or diabetes and for individuals at high CVD risk Target values for patients with established CVD or diabetes and for individuals at high CVD risk The characteristics of a heart-healthy population are shown in Table 1. More rigorous BP and lipid control is desirable in persons at the highest risk, particularly those with established CVD and with diabetes mellitus (Table 2). There is overwhelming evidence for an adverse effect of smoking on health [11]. It is responsible for 50% of all avoidable deaths and one half of these are because of CVD [12, 13]. Even passive smoking has now been shown to increase the risk of coronary heart disease and other smoking-related diseases [14, 15]. Smoking cessation leads to a quick reduction in the risk of subsequent coronary heart disease events in patients with established CVD: the risk falls within 2–3 years to the level of those coronary heart disease patients who never smoked [16]. It is potentially the most effective of all preventive measures after a myocardial infarction. Smoking cessation after a myocardial infarction showed a mortality benefit with a combined odds ratio of 0.54 (95% confidence interval 0.46–0.62). The assessment of the smoking status should be done at every opportunity; stopping should be encouraged in all smokers. There is no age limit to gain the benefits of smoking cessation. For the individual, a combined behavioural and pharmacological intervention may be most appropriate, yet the public health impact may be greater by community-oriented interventions. Nicotine replacement therapy has been widely used to overcome the difficult initial phase of smoking cessation and quit rates increase approximately 1.5–2 fold [17]. There is a strong and graded relationship among saturated fat intake, blood cholesterol levels and the mass occurrence of CVD. Therefore, nutritional counselling is an integral part of cardiovascular prevention and all CVD patients or patients at high risk should be given recommendations on the food and dietary options that reduce risk. A varied and energy-balanced regimen is critical to the preservation of a good cardiovascular health. Sodium intake, especially in the form of sodium chloride, influences arterial BP and therefore the risk of arterial hypertension, stroke, CVD and heart failure. In societies with low salt intake there is no age-related increase in BP. A low-sodium diet helps in maintain of lower BP after withdrawal of antihypertensive drugs. Fruits and vegetables are significant sources of minerals, vitamins and fibres. Favourable relationships exist between regular consumption of fruits and vegetables and CVD. Alcohol is not an essential nutriment. There is also no reliable proof showing any higher cardiovascular benefit of any drink compared with another, and advocating the therapeutic use of alcohol is not recommended. General nutritional recommendations: Eating food from each major food group will ensure the appropriate supply in nutrient, minerals and vitamins. Energy intake should be adjusted to maintain ideal weight. The intake of fish, fruit and vegetables, cereals and grain products, skimmed dairy products and lean meat is encouraged. Eating oily fish and omega-3 fatty acids is particularly appropriate, as it has been associated with a reduction in risk of fatal cardiovascular accidents. Replacement of saturated and trans fatty acids with monounsaturated or polyunsaturated fats of vegetable origins decreases LDL-cholesterol. Eating fruit and vegetables and restricting salt is associated with lower BP. Obesity is becoming a worldwide epidemic and mortality rapidly increases with overweight [18]. Abdominal obesity is an independent contributor to cardiovascular risk, including stroke. The higher mortality rates are mainly because of cardiovascular complications, the impact of which is proportional to overweight and weight gain since youth. The waist measurement and the waist-to-hip ratio are simple appraisers of abdominal adiposity. Weight reduction is strongly recommended for obese individuals having a BMI ≥ 30 or ≥ 25 kg/m2 in the presence of cardiovascular risk factors. To do so, the caloric intake must be reduced and exercise needs to be taken. Reduced caloric intake is achieved at the expense of foods with high energetic density – food fats (9 kcal/g) and alcohol (7 kcal/g). Total fat intake should be restricted to 20–35% of energy. A reduction in saturated fats is the preferred target because of its effects on the lipoprotein profile. Successful weight reduction requires good motivation by the person and encouragement and long-term support by the physician. Many different diets have been proposed for the treatment of obesity: a Cochrane review of a person on low-fat diets concluded that fat-restricted diets are no better than calorie-restricted diets in achieving long-term weight loss in overweight or obese people [19]. A low-fat diet is still considered the standard approach to weight reduction but even a low-carbohydrate diet has become popular. In the short term, the low-carbohydrate diet results in greater decrease in body weight, an effect that is no longer detectable after 12 months. The low-fat diet has a more favourable effect on LDL-cholesterol, whereas the low-carbohydrate diet has a better impact on plasma triglycerides and HDL-cholesterol. A lack of regular physical activity may contribute to the early onset and progression of CVD. Assessment of physical activity should be an integral part of risk evaluation as health benefits occur with almost any increase in activity. Physical fitness has both a direct protective effect on the development of vascular lesions and an indirect effect through influencing other risk factors: lowering plasma LDL-cholesterol and triglycerides, increasing plasma HDL-cholesterol, reducing overweight and lowering BP levels. Thus, the promotion of regular physical activity at school, at the place of work, during leisure time and after old-age retirement is an important target for preventive cardiology [20]. Each child in Europe should have access to periods of physical activity each day, be it in school or during leisure time. Special efforts should be made to ensure that adolescents maintain a physically active lifestyle, using the available resources in society such as sports clubs, gymnasia, swimming pools and the like. Adults should be supported to increase their physical activity to the level associated with the lowest risk of CVD. It should be recommended to choose enjoyable activities which fit into their daily life, preferably for 30–45 min, 4–5 times weekly at a 60–75% of the age-adapted maximum heart rate. This level is easily achieved by exercises involving the large muscle groups, such as brisk walking or jogging, cycling, swimming, aerobic dancing, tennis, golf or even cross-country skiing. An encouraging recent trend is the observation that almost any increase in activity is associated with measurable health benefits, even before the manifestation of training effect and before any change in weight is evident. However, the recommended level of energy expenditure may be insufficient to prevent unhealthy weight gain and may therefore be increased up to 60 min daily and combined with caloric restrictions. For patients with established CVD and for those with a high CVD 10-year mortality risk, advice must be based on a comprehensive clinical judgment, including the results of an exercise test. Many patients will benefit from an organized rehabilitation programme provided by a multidisciplinary team [21]. These programmes, in addition to supervised physical exercise, give a good opportunity for a comprehensive evaluation of the patient's risk factor status and for further advice and measures aimed at risk reduction. If patients prefer to perform the physical training programme at home, they will need clear prescriptions, encouragement and regular follow-up by their physician. Devices such as heart rate monitors or pedometers may be helpful in the follow-up of a home-based programme for physical training. The key elements of activity programmes for the elderly are: a combination of endurance, strength, balance and flexibility training. Brisk walking at a pace at which a conversation can still be held (‘walk-and-talk model’) is a good example of advice for the healthy elderly. Elderly patients with signs of CVD will benefit from comprehensive rehabilitation programmes; exercise training is safe and improves strength, aerobic fitness, endurance and physical function. It will improve conventional risk factors, mental state and quality of life [22]. Elevated BP has been identified as a risk factor for CHD. Increased risks are present in age groups from 40 to 89 years old. For every 20 mmHg systolic or 10 mmHg diastolic increase in BP, there is a doubling of mortality from both CHD and stroke. Individuals with an elevated BP are more likely to have other risk factors for CVD and because risk factors may interact positively with each other, the overall cardiovascular risk of hypertensive patients may be high even if BP is only moderately raised [23]. BP can be reduced either by lifestyle interventions and/or by drugs. In nonhypertensive individuals, including those with high to normal BP, dietary changes that lower BP have the potential to prevent hypertension and thereby lower the risk of BP-related clinical complications. A substantial body of evidence strongly supports the concept that multiple dietary factors affect BP. Modifications that lower BP are reduced salt intake, weight loss and moderation of alcohol consumption. The effects of sodium reduction on BP tend to be greater in blacks, middle-aged and older persons and in individuals with hypertension, diabetes or chronic kidney disease. Being overweight may influence BP. In one meta-analysis, mean systolic and diastolic BP reductions associated with an average weight loss of 5.1 kg were 4.4 and 3.6 mmHg, respectively [24]. Higher levels of physical activity and greater fitness are associated with a reduced incidence of hypertension. The BP-lowering effects of exercise are most pronounced in hypertensives engaging in endurance exercise with BP decreasing approximately 5–7 mmHg after an isolated exercise session (acute) or after exercise training (chronic). For hypertensive individuals, an exercise programme that is primarily aerobic based with adjunctive resistance training is recommended [25]. The evidence is limited regarding frequency, intensity and time recommendations; the antihypertensive effect seems to occur at relatively low duration and intensity. In general, the diagnosis of hypertension should be confirmed with a minimum of two BP readings and carried out in the sitting position from the right or the left arm, after the patient has rested for 5 min. Ambulatory BP monitoring (ABPM) provides information about BP during daily activities and sleep. In population studies, office values of 140/90 mmHg correspond approximately to 24-h average values of 125–130/80 mmHg. These values may be regarded as approximate threshold values for diagnosing hypertension. Most hypertension guidelines accept the superiority of 24-h ABPM over the office BP in diagnosing hypertension. Therefore, it may be desirable to include 24-h ABPM into the diagnostic algorithm of guidelines for hypertension management [26]. Home BP measurements for suitable periods (e.g. a few weeks) before and during treatment may be recommended as this may improve patient's adherence to treatment regimens [27]. Most of the cholesterol in blood plasma is normally carried in LDL and there is a strong and graded positive association between total as well as LDL-cholesterol and CVD risk. Reduction of measured LDL-cholesterol must be a prime target for the prevention of atherosclerotic disease. LDL can be measured directly, but it is usually calculated by the Friedewald formula [28]. Hypertriglyceridemia is also associated with CVD risk but this association is no less strong. A triglyceride value greater than 1.7 mmol/l (approximately 150 mg/dl) is considered a marker of increased risk, but concentrations less than 1.7 mmol/l are not considered a goal of therapy. Low concentrations of HDL-cholesterol are clearly associated with early development of atherosclerosis and also with poor outcome in patients with established CVD [29, 30] HDL-cholesterol is not considered a goal of therapy. Instead, HDL-cholesterol less than 1 mmol/l (40 mg/dl) in men and less than 1.2 mmol/l (40 mg/dl) in women is considered a marker of increased risk; here attention to lifestyle might be needed. Apolipoprotein B (apoB) is the major protein component of LDL, intermediate density lipoprotein (IDL), very low density lipoprotein (VLDL) and, in truncated form, chylomicrons. It is a useful risk indicator, particularly in those with hypertriglyceridemia [31] and in people with normal concentrations of LDL-cholesterol [32]. Values greater than 150 mg/dl are clearly associated with increased risk. ApoA1 is the major apoprotein of HDL. Low concentrations of apoA1 are, such as low HDL-cholesterol, associated with higher risk of CVD. It is beyond doubt that the apoB/apoA1 ratio is one of the strongest risk markers, although it has been shown that the prognostic power does not change when total cholesterol/HDL ratio is replaced by apoB/apoA1 ratio. The ratio of either total cholesterol or LDL-cholesterol to HDL-cholesterol does not predict cardiovascular events better than the simple measurement of total cholesterol [33]. Hyperlipidemias secondary to other conditions must be excluded before the beginning of treatment. All CVD patients and persons at high risk should follow the dietary and physical activity recommendations given in this document. Regular exercise has been proven to be a powerful means for reducing total and LDL-cholesterol as well as triglycerides. For the target values of therapy in a healthy population see Table 1, for patients with established CVD or diabetes and for those at high CVD risk see Table 2. High doses of statins should not be used in primary prevention. It has been shown that progression to diabetes can be prevented or delayed by lifestyle intervention in persons with impaired glucose tolerance. Good metabolic control prevents microvascular complications but the picture is less clear in relation to macrovascular disease. In type I effects of metabolic control on the risk of CVD has been but this be an effect through the effect on microvascular complications. In type the evidence strongly an effect of glucose control on the risk of CVD. there is to aim for good glucose control in both of In type I glucose control requires appropriate therapy and dietary therapy. In type dietary reduction of overweight and increased physical activity should be the treatment by treatment. treatment for type diabetes are given in Table The metabolic the of CVD risk factors in individuals with obesity or It does not risk of CVD over and the effect of the risk factors It can be the given by the or more of the greater than in greater than in triglycerides ≥ 1.7 mmol/l 150 HDL-cholesterol than mmol/l mg/dl) in or than 1 mmol/l 40 mg/dl) in BP ≥ mmHg, glucose ≥ mmol/l mg/dl) or in patients with diabetes mellitus type Diabetes and in patients with diabetes mellitus type Diabetes and has a strong influence on all the components of the metabolic and the should be on lifestyle particularly efforts to reduce body weight and increase physical activity. The diagnosis of the metabolic is of in individuals as an of an increased risk of type 2 diabetes and CVD. CVD risk assessment such as and other risk maintain their primary place in the of individuals who are at high CVD. The components of the metabolic with the of the measures of obesity, are among the risk factor measurements used in these waist measurement to this will give to the presence of the metabolic and people who are at high risk of CVD, although they do not particularly high risk in conventional CVD risk