Introduction
After an alarming rise in the mortality from atherothrombotic
cardiovascular disease (CVD) in the 1950s in most industrialised
countries, the CVD epidemic levelled off and an impressive decline
started. That decline has occurred in most European countries,
commencing earlier in some compared to others [1]. The majority of the
reduction in CVD mortality rates is attributable to preventive efforts
more than to changes in care [2]. However, the epidemic is still very
dynamic in different parts of the world and changes may again occur in
the wrong direction; it was recently reported that the rate of decline
in CVD mortality has decelerated in the USA [3] and was absent in young
adults in Norway [4].
It could also well be that prevention of CVD in the present
generation of adults is to a certain extent only a postponement of
events or a reduction of the case fatality rate rather than a complete
prevention. Prevention of premature CVD mortality and of disability
adjusted life years (DALYs) is great but could be associated with an
increase in the prevalence of CVD in the elderly and in the very old,
with an epidemic of end-stage CVD such as chronic heart failure, renal
insufficiency and vascular dementia with all its consequences in terms
of more need for care than for cure and of increasing healthcare costs.
Therefore, more should be invested in the earliest possible
prevention of CVD from childhood onwards, in the prevention of the
development of an increased total CVD risk. This can be achieved by
aiming for a non-smoking generation of adolescents who keep physically
active throughout life and preventing the development of overweight and
obesity.
Lifestyle, behaviour, socio-economic issues
Societal changes may affect the CVD epidemic in different ways.
Globalisation, migration, socio-economic changes and unemployment may
have influences. Differences in CVD health among countries, regions and
neighbourhoods have increased over the years; these inequalities can be
explained by components of human behaviour such as diet, exercise,
smoking and job-related features but also by overcrowding, unemployment
and other indicators of deprivation. Life expectancy increases
continuously with income. In the USA at the age of 40 years, the gap in
life expectancy between individuals in the top and bottom 1% of the
income distribution is 15 years for men and 10 years for women. Most of
the variation in life expectancy across areas was related to differences
in health behaviour, including smoking, obesity, and exercise [5].
Smoking of tobacco
Tobacco smoking remains the single most important preventable cause
of premature mortality and of DALYs, and quitting smoking is the most
cost-effective strategy to prevent CVD. Improvements have been made
regarding the smoking of tobacco, in some countries more than in others,
with large differences according to socio-economic class. Governmental
restrictions and regulations have been successful; high taxes on tobacco
products are the most effective policy measure to reduce smoking in the
young. However, this needs to be complemented by continuous health
education campaigns particularly targeted at the young and other
subgroups of society. Restrictions on advertising, promotion and
sponsorship by the industry are needed.
Smokers who want to quit should receive professional assistance if
required. Brief interventions with advice to stop smoking together with
pharmacological support and follow-up visits are effective and safe but
insufficiently applied, even in smokers with established coronary heart
disease [6]. If a smoker is willing to stop, a quitting plan should be
prepared including a quit date, information to friends and family asking
for support, removal of all tobacco and of objects associated with
smoking behaviour from the immediate surroundings, and finally
arrangement of follow-up visits, ideally within the month and every
month thereafter for four months. At the follow-up visit the person
should be congratulated if he/she had stopped smoking. In case of
relapse, a more intensive approach should be considered, such as
referral to a smoking cessation specialist or centre.
If advice, encouragement and motivation are likely to be
insufficient, drug therapies should be considered early on, including
nicotine replacement therapy (NRT), bupropion or varenicline. Smoking
cessation pharmacotherapy may double or triple quit rates, and combining
pharmacotherapy with counselling improves quit rates further.
The success rate of stopping smoking with varenicline is higher than
with bupropion; varenicline doubles the chances of stopping smoking
compared to placebo [7]. Varenicline reduces craving for cigarettes and
withdrawal symptoms; it should be started one to two weeks before the
quit date. Hypersensitivity is the only contraindication. Nausea is the
most common side effect, especially at the start of therapy and if taken
together with food. Titration of the dose may be necessary in some
cases.
Electronic cigarettes, or e-cigarettes, can deliver high
concentrations of nicotine as a vapour and have been recommended as a
measure to help cessation of smoking of regular cigarettes. Results of
studies on the cardiovascular effect of e-cigarettes are inconsistent
but an increased risk has been documented in some [8].
Avoidance of passive smoking is another strong recommendation for the prevention of CVD.
Diet
Regarding the dietary habits of the population, changes have occurred
in different areas. For example, the intake of salt and saturated fats
has been reduced in most societies. The food industry has reduced the
presence of trans fatty acids in different food items; this has been
promoted by regulatory initiatives in some communities. However, the
potential to prevent CVD through dietary adaptations is still poorly
implemented. Adherence to a balanced diet is generally limited; the
control of elevated blood pressure, dyslipidaemias and dysglycaemia can
largely be improved through changes in lifestyle. Achieving better
adherence with dietary recommendations requires the understanding of the
determinants of poor compliance. At the population level, structural
measures such as product information, and consumer-friendly nutrition
labelling may improve health-friendly choices. Energy-dense,
nutrient-deficient foods are generally highly accessible and
inexpensive; the marketing of such foods could be limited and taxed. On
the other hand, fruits and vegetables tend to be more expensive; the
subsidising of their costs may be useful.
At the clinical level, general practitioners have an opportunity to
provide counselling about diet for the management of coronary risk
factors. However, barriers to that were reported related to time
limitations, knowledge and perceived efficacy [9]. The extent to which
physicians are familiar with a healthy dietary pattern (i.e., DASH,
Mediterranean diet) and with translating that information into practical
recommendations may be limited. A multidisciplinary approach including
nutritionists and dieticians may help but needs improved reimbursement
coverage.
At the individual level, new strategies may help to improve patient
self-management and to induce sustainable behaviour change. Many apps
and devices are available that provide data that can be useful for
lifestyle changes and patient self-management. In Table 1 dietary
targets of a well-balanced diet to prevent CVD are summarised.
Table 1. Dietary targets to prevent CVD.
| Dietary targets to prevent CVD |
* Consume more fruit, nuts, seeds, vegetables; 2 to 3 servings of each per day.
* Limit the consumption of saturated fatty acids to <10% of total
energy through replacement by poly-unsaturated fatty acids (PUFA).
* Use vegetable oils rich in PUFA and soft spreads based on e.g., soybean oil, canola oil and extra-virgin olive oil.
* Limit the consumption of refined grains and sugar; aim at 30-45 gr of fibre per day, preferably from wholegrain products.
* Consume 1 or 2 servings of fish per week, preferably oily fish such as sardines, herring, tuna, salmon, mackerel, trout.
* Don’t eat processed meat; limit the consumption of fresh red meat to 2-3 servings per week.
* Avoid foods made with partially hydrogenated vegetable oils aiming at a zero consumption of trans unsaturated fatty acids.
* Avoid drinking sugar-sweetened beverages.
* Limit the intake of sodium aiming at <5 gr of salt per day.
* If alcohol is consumed it should be limited to 2 glasses per day
(20 gr alcohol) in men and to 1 glass per day (10 gr alcohol) in women.
|
Physical activity
The promotion of physical exercise is a crucial and central issue in all strategies of CVD prevention.
At the individual level, physical activity should be advised at
different time points; it should become part of regular life from
childhood onwards. Children and adolescents should be encouraged to
spend 30 to 45 minutes daily in exercise activities either at school or
in their leisure time. This should be maintained for as long as possible
through young adulthood.
Healthy adults in all age groups are recommended to choose enjoyable
physical activities which fit in with their daily routine on most days
of the week. They are recommended to engage in at least 150 minutes a
week of moderate aerobic physical activity (30 minutes for 5 days/week)
or 75 minutes a week of vigorous aerobic physical activity (15 minutes
for 5 days/week) or a combination thereof. At the individual level,
exercise prescription should be more personalised. Therefore, a short
history of the physical activity level of the individual is needed (how
many minutes per day spent on average in activities at moderate or
vigorous intensity). On that basis and considering individual choices,
advice can be given on the most appropriate types of activity, on how to
progress, on which goals to set in order to achieve and maintain the
health benefits of an active lifestyle. Barriers towards achieving a
more active lifestyle as perceived by the individual should be
identified and ways of overcoming them should be explored. For people at
work, active travelling should be recommended as well as taking active
breaks from prolonged periods of sitting. Based on results from a
meta-analysis of 16 studies with more than one million individuals, it
was shown that one hour of activity offsets the risk from eight hours of
sitting [10]. In people unable to meet the minimum, or in sedentary
subjects who just start some activity, even the lowest recommended level
should be encouraged. It should be stressed that any increase in
activity will be associated with a health benefit, even before a
training effect is evident, and that it is fine to work progressively
towards any given target.
Management of CVD risk factors
All current guidelines on the prevention of CVD in clinical practice
recommend the assessment of total CVD risk because atherosclerotic CVD
is usually the product of a number of risk factors. Prevention of CVD in
a given person should be adapted to his or her total CVD risk: the
higher the risk the more intensive the action should be. The
stratification of the community into different levels of total CVD risk
was given in recent guidelines [11].
Dyslipidaemias
Randomised controlled trials (RCTs) have clearly demonstrated that
reducing the low-density lipoprotein-cholesterol (LDL-C) level with diet
and/or lipid-lowering drugs can reduce the risk of CVD events. This
evidence is greatest for the use of statins. In other RCTs, more versus
less LDL-C reduction was studied in coronary patients, resulting in more
CVD prevention with more intensive statin therapies [12]. It was also
shown that a gradient exists between the degree of lowering LDL-C and
the magnitude of CVD prevention [13].
The treatment goals for LDL-C depend on the total CVD risk of the
patient and of the baseline LDL-C level. In patients at very high CVD
risk, an LDL-C goal of <1.8 mmol/L (70 mg/dL), or a reduction of at
least 50% if the baseline LDL-C level is between 1.8 and 3.5 mmol/L (70
and 135 mg/dL), is recommended.
In patients at high CVD risk, an LDL-C goal of <2.6 mmol/L (100
mg/dL), or a reduction of at least 50% if the baseline LDL-C level is
between 2.6 and 5.2 mmol/L (100 and 200 mg/dL), is recommended. In
subjects at moderate risk, an LDL-C goal of <3.0 mmol/L (115 mg/dL)
should be considered.
Based on the results of the IMPROVE-IT trial, further LDL-C lowering
by adding ezetimibe should be considered in CVD patients with an LDL-C
≥70 mg/dL (≥1.8 mmol/L) despite the maximally tolerated dose of statin
[14]. A new family of lipid-lowering drugs has now become available.
These proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9)
reduce LDL-C further in addition to what can be achieved with statins.
In the FOURIER trial, the inhibition of PCSK9 with evolocumab on a
background of statins lowered LDL-C to a median of 30 mg/dL (0.78
mmol/L), and reduced CVD events [15].
The use of this drug should be considered in patients at very high CV
risk in whom LDL-C remains elevated despite being treated with a
maximal statin dose in combination with ezetimibe, or in patients with
statin intolerance.
Arterial hypertension
Elevated blood pressure (BP) is one of the most powerful modifiable
risk factors for CVD. The beneficial effects of BP-lowering therapies to
reduce stroke, myocardial infarction, heart failure and death have been
shown in numerous RCTs and in different meta-analyses [16]. BP lowering
can be achieved through lifestyle changes and drug therapies.
Results from post hoc analyses of trials from the past suggested the
existence of a J-shaped association between achieved BP and CVD risk.
Results from more recent trials [17,18], where more intense BP lowering
was compared with less intense reduction, have re-opened the discussion
regarding the most optimal BP goals to achieve in patients with arterial
hypertension. In a recent systematic review and network meta-analysis
including 42 trials and 144,220 patients, it was found that reducing
systolic BP to levels below the BP targets that were recommended
previously reduces the risk of CVD and all-cause mortality [19]. All
this calls for BP lowering based on the patient’s potential to benefit
without harm rather than on reducing the BP to a specific target.
Therefore, in patients at very high risk, as is the case in the presence
of CVD, BP lowering may require more intensive strategies than those
currently recommended in the guidelines. However, this should be decided
on a more personalised basis. Lower treatment targets are also
associated with a higher medication burden and with an increased risk of
side effects.
Recommendations regarding BP targets in patients with arterial
hypertension, based on the 2016 ESC guidelines on CVD prevention in
clinical practice [11], are given in Table 2.
Table 2. Blood pressure targets for patients with arterial hypertension.
| Blood pressure targets for patients with arterial hypertension |
* SBP <140 mmHg and diastolic blood pressure (DBP) <90 mmHg are
recommended in all treated hypertensive patients <60 years old.
* In patients >60 years old with SBP >=160 mmHg it is recommended to reduce SBP to between 150 and 140 mmHg.
* In fit patients <80 years old, a target <140 mmHg may be
considered if treatment is well tolerated. In some of these patients a
target SBP <120 mmHg may be considered if at (very) high risk and if
multiple blood pressure-lowering drugs are well tolerated.
* In individuals >80 years old and with initial SBP ≥160 mmHg, it
is recommended to reduce SBP to between 150 and 140 mmHg provided they
are in good physical and mental condition.
* In frail elderly patients, a careful treatment intensity (e.g.,
number of blood pressure-lowering drugs) and blood pressure targets
should be considered, and clinical effects of treatment should be
carefully monitored.
* Beta-blockers and thiazide diuretics are not recommended in
hypertensive patients with multiple metabolic risk factors due to the
increased risk of diabetes mellitus.
* Blood pressure targets in type 2 diabetes mellitus are generally
recommended to be <140/85 mmHg but a lower target of <130/80 mmHg
is recommended in selected patients (younger patients at elevated risk
for specific complications) for additional gains on stroke, retinopathy
and albuminuria risk. Recommended blood pressure target in patients with
type 1 diabetes mellitus is <130/80 mmHg.
|
Dysglycaemia
In people with impaired glucose tolerance, the development of type 2
diabetes mellitus (DM) can be postponed or prevented. In patients with
type 2 DM, CVD events can be prevented through good control of CVD risk
factors. Intensive management of hyperglycaemia will also reduce the
risk of microvascular complications.
Unfortunately, the prevalence of type 2 DM is increasing in most
parts of the world, mainly due to unbalanced diets and a lack of
physical activity. The diagnosis of DM is also still problematic in a
large number of individuals, and even in patients with established CVD
[6]. Screening should be considered by assessing HbA1c or fasting blood
glucose. When there is still doubt, an oral glucose tolerance test
should be offered.
For the majority of non-pregnant adults with either type 1 or type 2
DM, a target of HbA1c of < 7.0% (< 53 mmol/mol) is recommended to
reduce CVD risk and the risk of microvascular complications. At
diagnosis, or early in the course of type 2 DM, a target of HbA1c of ≤
6.5% (≤ 48 mmol/mol) should be considered in patients who are not frail
and do not have CVD.
Metformin is recommended as first-line therapy if tolerated and not contraindicated following the evaluation of renal function.
In patients with DM and CVD, the use of sodium-glucose
co-transporter-2 (SGCT2) inhibitors reduced CVD and total mortality
without major adverse effects [20]. These drugs should be considered
early in the management of DM in these patients.
Optimal control of the LDL-C level and of the BP is of great importance in all patients with DM (see above).
Conclusions
Prevention of atherothrombotic CVD has been a success story in
medicine and public health; however, challenges remain related to
residual CVD risk, environmental factors, the ageing of the population
and poor adherence to recommendations regarding CVD prevention. Some of
these factors relate to human behaviour and to socio-economic features.
Tackling these “causes of the causes” is a major challenge at national
and international level. More research should also be focused on the
(cost-) effectiveness of preventive strategies. The potential for
further gains in preventing CVD is important. It is up to society to
make the best use of it.
Our mission: To reduce the burden of cardiovascular disease
