Lifestyle Interventions

Epidemiology

Smoking is a strong risk factor for coronary heart disease and, due to a persistently high use of tobacco products, remains responsible for a large proportion of coronary heart disease cases. In the INTERHEART study the population attributable fraction for smoking in causing MI was 35.7%. Smoking has declined in the Western world in recent decades, and this decline has been an important contribution to the observed decline in mortality from coronary heart disease. Nonetheless, it is estimated that active and passive smoking remains responsible for more than 480,000 annual deaths in the United States, equivalent to one in five deaths, almost half of these from CVD.

The decline in smoking has been greatest among light smokers, men, and the socioeconomically privileged, leading to increased disparities in smoking-attributable disease. Even in smokers with established coronary heart disease many continue to smoke. European survey data indicate that 16% of patients with coronary heart disease are smokers more than one year after their event, and only half of smokers have quit smoking. The survey also found that smoking cessation tools were underused.

Types, Dosage, and Passive Smoking

Smoking is a strong and independent risk factor for all CVD. Smokers on average reduce their life span by 10 years, and their risk of developing CVD is increased two- to threefold. In younger smokers the excess risk is five times higher than in nonsmokers of similar age. All types of tobacco are deleterious, whether low-tar (“mild” or “light”), filter cigarettes, pipe, or cigar. Moreover, significantly increased risk is still seen in smokers that have limited inhalation of smoke, such as habitual pipe or cigar smokers. There is no lower limit below which smoking is safe. Passive smoking or environmental tobacco smoke also increases the risk of smoking-related diseases. For example, work-related exposure to environmental tobacco smoke has been reported to increase the risk of MI by approximately 20% to 30%. The deleterious effect of environmental tobacco smoke is corroborated by animal and mechanistic studies showing measurable levels of tobacco and nicotine degradation substances in blood and urine of passive smokers and a measurable effect on endothelial function and platelet aggregation in study subjects exposed to passive smoking. Correspondingly, since legislation on passive smoking has been implemented in various settings, the rate of MI has dropped by an estimated 17%. This decline in incidence of MI was seen mainly among nonsmokers. These data indicate that patients at increased risk of CVD, including post-MI patients, should be advised to avoid exposure to environmental tobacco smoke. Smokeless tobacco, which is popular in some subgroups as, for example, “snus” (a moist powder tobacco placed under the upper lip), is also associated with a small but significantly increased risk of MI and stroke.

Mechanism

The effects of smoking on cardiovascular pathogenesis are several. When tobacco is burned, thousands of chemical compounds are developed and inhaled. These chemical compounds have numerous effects on the cardiovascular system. Smoking acts chronically by accelerating the atherosclerotic process and acutely by increasing the risk of plaque rupture and thrombus formation. Central to the effects of smoking is increased oxidative stress and endothelial dysfunction and injury ( Fig. 18.1 ). The atherosclerotic plaques of smokers are more vulnerable with unfavorable plaque lipid composition, more inflammatory activity, degradation of extracellular matrix proteins, and thinner fibrous caps through inappropriate activation of matrix metalloproteinases and higher risk of intraplaque hemorrhage. Smoking exposure affects the balance of procoagulant and anticoagulant factors leading to a prothrombotic state with increased platelet activation, activation of coagulation pathways, and downregulation of fibrinolytic pathways. These mechanisms also lead to higher risk of in-stent thrombosis in smokers, and prothrombotic effects are amplified by concomitant oral contraceptive use. Further effects include changes in vasomotor function through impairment of endothelial function, increased leucocyte count, and lowering of high-density lipoprotein cholesterol (HDL-C).

Corresponding to these effects, after smoking cessation cardiovascular risk decreases in a biphasic manner with rapid onset of reduction through decreased propensity to thrombus formation and increased plaque stability, followed by more long-term effects in reduced atherosclerosis disease progression. The first beneficial cardiovascular effects of smoking cessation are also seen very soon after quitting: within hours, heart rate (HR) drops and carbon monoxide returns to normal; within days to weeks, effects on platelet and endothelial function are reversed. Correspondingly, the risk of recurrent events after quitting immediately drops. In a study of smoking cessation after MI, smokers who had quit within the first month had a 43% reduced risk of recurrent events within the next 5 months in comparison with continuing smokers. This first risk reduction is followed by a more prolonged effect, and epidemiologic studies have shown that the risk of recurrent events in ex-smokers approaches that of never-smokers asymptotically by 15 to 20 years. Although the atherosclerotic plaque is not dissolved after smoking cessation, plaque stability is increased and plaques are less prone to rupture and erosion causing MI.

Smoking Cessation Benefits

Evidence of effects of quitting smoking are based on observational studies of smoking cessation among the general population as well as cardiac patients. Smokers who give up smoking in the context of a cardiovascular event differ from smokers who continue smoking with regard to other aspects associated with cardiovascular risk: they are, for instance, also more likely to adhere to other lifestyle changes and to medication. Therefore, these studies have the inherent risk of overestimating the benefits of smoking cessation. However, given the strong evidence of the effects of smoking from basic science, animal studies, and observational studies, as well as short-term mechanistic intervention trials, the evidence supporting cardiovascular benefits and general health benefits of smoking cessation is overwhelming.

In a smoker, smoking cessation is potentially the lifestyle change with greatest impact on risk of recurrent events. Because smoking has such profound effects on overall health status, the benefits of cessation are multiple. Quitting smoking in patients with coronary heart disease was associated with a 36% reduced mortality risk and a 32% reduced risk of fatal MI when compared with continued smokers in a large meta-analysis ( Fig. 18.2 ). This benefit was consistent across gender, age, and duration of follow-up. Due to the relatively small effect of the intervention on smoking prevalence, large-scale randomized smoking cessation trials are generally required. The few existing randomized controlled trials of smoking cessation with mortality or morbidity outcomes indicate effects similar to those reported in the observational meta-analyses.

Smoking Cessation Aid

Smoking cessation is difficult to achieve because the habit is strongly addictive pharmacologically and psychologically and is enforced by smoking habits in the family and social environment of the patient. The most important predictor of successful smoking cessation is patient motivation. Studies have shown that other factors also affect the likelihood of quitting smoking; women, the socioeconomically deprived, and patients with depressive symptoms are less likely to achieve their goal. As with other lifestyle changes, support from the surrounding environment, including through antitobacco legislation and policy changes, is important for sustainable effects.

To achieve smoking cessation, health professionals should give a strong, clear, and consistent message to the patient. Smoking habits should be addressed in all contact with patients with CVD and smokers should be encouraged to quit, regardless of age. Contacts with the patient during hospital admission for a cardiovascular event or for revascularization are moments of opportunity to reinforce the message. Notably, brief advice from health physicians, nurses, and other health professionals are evidence-based interventions that increase the likelihood of quitting by 60% to 70%. Allied health professionals should assess nicotine addiction and degree of patient motivation, set a quit date, and arrange follow-up (see the five As in Table 18.1 ). Smokers should be informed that smoking cessation is accompanied by a mean weight increase of 5 kg but that the health benefits of smoking cessation far outweigh the effects of potential weight gain.

The majority of smokers who quit do so unaided. Individual, group, and telephone counseling increase quit rates, whereas smoking reduction, nicotine fading, relaxation techniques, hypnosis, and acupuncture are methods that have not been proven successful in trials. Quitting rates can be increased by use of pharmacologic agents diminishing withdrawal symptoms in addicted smokers ( Table 18.2 ). Nicotine replacement therapy, the mild antidepressant bupropion, and the partial nicotine agonists varenicline and cytisine have all been shown to increase quit rates. Nicotine replacement therapy, whether delivered as gum, transdermal patch, nasal spray, lozenge, or inhaler, increased the success rate by 84%. Bupropion had similar effects (quit rate increased by 82%), confirmed by head-to-head comparison studies. Varenicline has mainly been tested against singular nicotine replacement therapy and shown to result in an approximately 50% higher success rate. However, combination therapies of nicotine replacement therapy are more efficient than singular use. A combination of varenicline and nicotine replacement therapy may be superior to either used alone. Cytisine, although less studied, has been found to increase quit rates and may be more clinically effective and cost-effective than varenicline, although they have not been compared head to head. Cytisine is not approved for smoking cessation aid by regulatory authorities outside Eastern Europe. There was initial concern regarding possible minor adverse effects of varenicline on CVD outcomes, but these adverse effects have not been confirmed and nicotine replacement therapy, bupropion, and varenicline are currently all considered safe agents to use, including in cardiac patients.

E-Cigarettes

Electronic cigarettes (e-cigarettes) have been recently introduced and have achieved increasing popularity. The e-cigarette is an electronic vaporizer for delivery of nicotine. Because nicotine is addictive, e-cigarettes can be regarded as either a smoking cessation pharmaceutical and treated under pharmaceutical legislation, or as a tobacco product covered by regulations for tobacco products. Long-term nicotine addiction and usefulness of e-cigarettes as a smoking cessation tool have not yet been clarified. Currently, there is insufficient evidence that e-cigarettes are efficient in supporting smoking cessation. Concerns have been voiced of an increasing likelihood of nicotine addiction in youth if e-cigarettes are perceived as socially acceptable. However, e-cigarettes have been used as a means of reducing deleterious effects of smoking for smokers who are unable or unwilling to quit. Whereas there is little doubt that e-cigarettes are less harmful than smoking cigarettes, the long-term consequences are not known, and, at the time of writing, guidelines on both sides of the Atlantic recommend care. However, short-time use has not been associated with health risks.

Mediterranean and Other Diets

The Mediterranean diet is a diet similar to the traditional dietary patterns in Greece, Italy, and Spain. The diet was first described as beneficial in the seven countries study in which the diet in the Greek island of Crete was studied. The Mediterranean diet is defined as a diet rich in olive oils, fruit, vegetables, legumes, unrefined cereals, and fish; a moderate consumption of wine and dairy products (cheese and yogurt); and a relatively low consumption of meat. Mediterranean dietary patterns tend to be moderate in total fat, low in saturated fat, and high in fiber and polyunsaturated fatty acids, including n-3 (omega 3) fatty acids from fish consumption. The Mediterranean diet has been declared by UNESCO to be on the Representative List of the Intangible Cultural Heritage of Humanity of the Mediterranean countries Portugal, Spain, Italy, Croatia, Greece, and Morocco.

The evidence for the beneficial effect of the Mediterranean diet comes from multicenter observational studies and meta-analyses and also from randomized controlled trials. Meta-analyses of observational studies of the Mediterranean diet in primary prevention have found reduced incidence of diabetes, lower triglyceride concentrations, lower blood sugar levels, and lower blood pressure. Recent meta-analyses comprising data from more than 4 million individuals found significant reductions of overall mortality of 8% and of CVD morbidity of 10%. It should be noted, however, that two Cochrane reviews in 2013 found only limited evidence to date in randomized trials that the Mediterranean diet or increased fruit and vegetables consumption had a beneficial effect on CVD risk.

The two main trials showing a benefit of the Mediterranean diet on cardiovascular outcomes are the Lyon Diet Heart study and the Prevención con Dieta Mediterránea (PREDIMED) trial. Based on these trials, the plausibility through mechanistic studies, and the overwhelming evidence from observational studies, 2016 guidelines for secondary prevention recommend a diet that is close to the Mediterranean diet ( Box 18.1 ).

The PREDIMED trial was a Spanish multicenter trial comparing three diets: two arms with a Mediterranean diet supplemented with either extra virgin olive oil or mixed nuts, and one arm with a low-fat diet, in 7447 persons without CVD but at high risk of developing CVD. The Mediterranean diet recommended was rich in olive oil, nuts, fruit, vegetables, legumes, fish, and wine and low in soda drinks, bakery items, red meat, and spread fats. The low-fat diet arm also recommended fruit, vegetables, and fish/seafood in addition to low-fat dairy products and potatoes, pasta, and rice, whereas fatty fish, olive oil, and nuts were discouraged. The study was halted after 4.8 years after an interim analysis finding the Mediterranean diet superior. There was an overall 30% reduction in the primary major adverse cardiac event (MACE) outcome of MI, stroke, or death from CVD causes with similar risk reduction in the nut group and in the extra virgin olive oil group. The absolute risk in the PREDIMED study, although based on individuals with risk factors for CVD, was low, with overall CVD event rate in the range of 4% per year. The main event driving differences between groups was stroke. The reductions achieved were reported to be consistent with that calculated based on the PREDIMED population applying risk reductions achieved from observational studies on individual dietary components.

The PREDIMED trial has also been criticized. These criticisms include that it was halted early and that effects were seen in the beginning of the trial only and were exclusively mediated by reduction in stroke. Also, critics have suggested that the control diet was not only low in fat but also high in carbohydrates, or that the control diet was not low enough in fat. Finally, the absolute risk reduction was limited and the overall strong conclusions are based on a relatively low number of events.

The PREDIMED study was a primary prevention study in high-risk individuals. The only secondary prevention study powered for CVD events was the Lyon Diet Heart Study in which 605 patients with MI were randomized to a recommendation of Mediterranean diet versus no specific study-based recommendation. This study was also halted early. The study found a risk reduction for the main outcome of cardiac death or MI of 73% after 27 months, and the effect was maintained after 4 years’ follow-up.

The effect of diet on CVD risk seems to be rapid with significant differences seen within one year, which is also consistent with observational population studies and with effect on intermediary outcomes in controlled feeding studies. As previously mentioned the potential mechanisms are multiple: the Mediterranean diet has been shown to reduce the prevalence of the metabolic syndrome and, in patients with diabetes, to improve glycemic control. This diet has also been shown to reduce intima media progression, reduce blood pressure, reduce low-grade inflammation, improve insulin sensitivity, and reduce use of antihyperglycemic medication. Importantly, although the Mediterranean diet also leads to improved weight control, the beneficial effects are not mediated via weight loss but primarily through dietary composition.

Other dietary patterns deemed beneficial are the Dietary Approaches to Stop Hypertension (DASH), also recommended by the American Heart Association (AHA). The DASH diet is high in vegetables, fruit, low-fat dairy products, whole grains, poultry, fish, and nuts and is low in sweets, sugar-sweetened beverages, and red meats. The DASH diet is rich in potassium, magnesium, and calcium, as well as protein and fiber, but lower in total fat than the Mediterranean diet. Vegetarian diets, which are also very low in total fat, have also been shown to be somewhat beneficial to CVD endpoints in observational studies and smaller trials. One problem with diets that are very low in fat is less enjoyment, and thus in some patient groups lower adherence to the diet.

Based on the totality of the evidence from observational studies and intervention studies on individual nutrients, as well as from the PREDIMED and DASH trials, there is worldwide consensus that healthy dietary patterns are of greater importance than single nutrients for the prevention of CVD.

Fatty Acids, Including Trans-Fat

Fatty acids (FAs) are available as saturated FAs, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). A higher intake of saturated FAs comes mainly from animal products, including meats and dairy products, and is associated with higher LDL-C, lower HDL-C, and higher risk of CVD. Conversely, a higher intake of PUFAs, in particular, is associated with a lower risk of CVD. Substitution of MUFAs for saturated FAs lowers LDL-C and, to some extent, HDL-C, but the evidence of a beneficial effect on CVD outcome is limited. Substitution of PUFAs for saturated FAs is associated with reduced risk, whereas substitution with carbohydrates is associated with a more diabetogenic risk profile, higher triglycerides, lower HDL-C, and a higher CVD risk.

A 2014 meta-analysis has questioned the harmful effect of saturated FAs intake and has led to considerable discussion. However, the key point is what the saturated FAs are replaced with, as previously described. Thus saturated animal fat should be replaced mainly by unsaturated fat, i.e., plant oils. These are key constituents in the Mediterranean diet. Prevailing dietary recommendations include consumption of food low in saturated fat, with saturated fat constituting a maximum of 10% of the total energy intake, or preferably less.

Dietary intake of cholesterol has a limited effect on serum lipoproteins, in comparison with the effect of FAs and carbohydrates, and most guidelines do not give a specific recommendation on cholesterol consumption.

Trans FAs are industrially developed products to stiffen liquid fats for spread. A higher trans FAs intake leads to higher LDL-C, lower HDL-C, and a higher risk of CVD. The association has been proven beyond doubt. Prevailing guidelines recommend no consumption of industrially produced trans FAs. Several countries have introduced legislation banning the use of trans FAs, and this ban may be associated with the steep decline in CVD mortality seen in some countries. In the United States, trans FAs have been classified as not safe by the Food and Drug Administration (FDA) and are being phased out from food production.

Polyunsaturated Fatty Acids, Fish, and Fish Oils

PUFAs include n-6 (omega 6) FAs, derived mainly from plant foods, and n-3 (omega 3) FAs, derived mainly from fish oils and fats. The n-3 FAs eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA) are particularly important subclasses of n-3 FAs. Dietary intake of fish is associated with lower risk of CVD. The association is not linear, with the highest risk seen for no fish consumption. The beneficial effect is thought to be mediated via the content of n-3 FAs. Several randomized trials in secondary prevention of CVD have tested the effect of supplementation with EPA/DHA in the form of fish oil capsules. These have not consistently shown a beneficial effect, and a lack of effect on CVD outcomes has been confirmed in a meta-analysis that included 20 secondary prevention trials with more than 60,000 patients. Overall, n-3 supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, MI, or stroke. The recommendation is thus to eat fish twice weekly or more, with one of the meals containing fatty fish, whereas fish oils may be used for reduction of triglycerides.