Cardiovascular disease prevention guidelines in clinical practice, reviewed.

Background

Cardiovascular disease (CVD) prevention is the basis for a healthy nation. With it, comes increased efficiency in the health care system and reduced medical costs. However, the Western world is facing increased diabetes and obesity and poor patients’ adherence to lifestyle changes. Furthermore therapy and evidence based CV prevention are not properly carried out (1). At a societal level, only 40% of dyslipidemia is controlled and fewer than 50% of hypertensive patients achieve target blood pressure in Euroaspire III (3), a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. 
To that effect, the latest ESC guidelines on CVD prevention (2012) state that prevention is effective: over 50% decrease in cardiac heart disease (CHD) mortality is brought on by changes in risk factors and around 40% by treatment strategies (1,2). A cardiovascular prevention program should carry out intensive work at a public health level with life-long measures that hold preventive actions from birth to old age. Here we offer a review of the guidelines as they go through a comprehensive handling of several distinct at-risk populations: 1) the total population, 2) high risk individuals and 3) patients after cardiovascular events. 

I - Assessing risk, implementing a program and using risk charts

In apparently healthy individuals, CVD risk is most frequently the result of multiple interacting risk factors such that cardiovascular prevention actions should be started and be guided by assessment of a patient’s total CV risk. To this effect, SCORE is recommended for risk assessment in the asymptomatic adult without evidence of CVD. The physician’s approach should aim to assess total risk and include all risk factor management as well as an individual approach for each person.  
In younger patients, low absolute risk may implicate a very high relative risk, and use of the relative risk chart may help in advising some of them to implement intensive lifestyle changes. Risk in women is deferred by approximately 10 years, and should not be neglected. 
In all patients, risk assessment should be repeated at 5-year intervals if the absolute CVD risk is low and/or there are no significant changes in the major risk factors.
Prevention efforts should be implemented in patients with established CAD (secondary prevention) or in individuals with one or more risk factors for CAD, family history of premature CVD, symptoms suggestive of CVD or socially deprived patients who might have increased burden of risk factors  (i.e. primary prevention). 
Patients with low a socio-economic status, stress at work and stress in family life, depression, anxiety, and individuals with a type D personality - a tendency towards distressed negative affectivity and social inhibition - contribute to the risk of CVD and worsening of CVD prognosis.
The SCORE system gives an estimate of the 10-year risk of a first fatal atherosclerotic event, whether heart attack, stroke, aneurysm of the aorta, or other vascular disease. The principles of risk estimation and management decisions must be interpreted in the light of both the physician’s detailed knowledge of patient and local guidance and conditions. 
Low-risk persons should be advised to maintain their low-risk status. Individuals with risk of CV death of ≥5% qualify for intensive advice, and may benefit from drug treatment. At risk levels >10%, drug treatment is frequently required. 
The relative risk chart may be helpful in young persons, even if absolute risk levels are low.

II - New items in the guidelines, use of imaging and less known risk causing diseases

Some new recommendations contained in the guidelines are that asymptomatic women and older people benefit from risk scoring to determine management:

• DNA-based tests for common genetic disorders are not recommended for risk stratification; anxiety and the type D personality increase risk for CVD and contribute to worse clinical outcome.
• Novel biomarkers have limited additional value when added to SCORE CVD risk assessment. 
• High-sensitive CRP may be used in subgroups of patients at moderate, unusual, or undefined levels of risk.

Within the context of prevention, imaging is used to improve CVD risk prediction by assessing subclinical CV disease. As such, the following noninvasive imaging methods should be considered in asymptomatic adults at moderate risk for atherosclerosis detection and additional CV risk stratification: 

1. Measurement of carotid intima-media thickness, screening for atherosclerotic carotid plaques and measurement of ankle-brachial index 
2. Computed tomography for coronary calcium assessment 
3. Exercise electrocardiography with attention to non-electrocardiogram markers such as exercise capacity.

Influenza vaccination as a population prevention measure was associated with a very cost-effective reduction in clinical CV events (4). Annual influenza vaccinations are recommended for patients with established CVD. In patients with chronic kidney disease, risk factors should be treated the same way as in very high risk persons. All persons with obstructive sleep apnoea should undergo risk stratification and risk management. Finally, men with erectile dysfunction should undergo CV risk stratification and risk management.

III – Recommendations on lifestyle changes, blood pressure targets and drugs 

Satisfactory cooperation with the patients is essential for successful life style changes. Principles of effective communication with patients are explained in details in the latest ESC guidelines on CV prevention.
All smoking including exposure to passive smoking is a strong and independent risk factor for CVD and has to be avoided. All smokers should be given advice to quit and be offered assistance.
Nutrition is related with increased prevalence of obesity, insulin resistance, and diabetes mellitus, endothelial dysfunction, which all lead to increased CV risk. 
A healthy diet has the following characteristics: 1) Energy intake should be limited to the amount needed to maintain a healthy weight, i.e. a BMI <25 kg/m2. 2) Daily saturated fatty acids intake should be <10% of total energy intake, replaced by polyunsaturated fatty acids. 3) <5 g of salt per day 4) 30–45 g of fiber per day, from wholegrain products, fruits and vegetables 4) 200 g of fruit per day (2-3 servings) 5) 200 g of vegetables per day (2-3 servings) 5) Fish at least twice a week, one of which to be oily fish. 6) Consumption of alcoholic beverages should be limited to 2 glasses per day (20 g/d of alcohol) for men and 1 glass per day (10 g/d of alcohol) for women.
Regular physical activity especially aerobic exercise training is associated with a decrease in cardiovascular mortality. 1) Healthy adults of all ages should spend 2.5-5 hours a week on physical activity of at least moderate intensity, or 1-2.5 hours a week on vigorous intense exercise. 3) Patients with previous myocardial infarction, CABG, PCI, stable angina pectoris or stable chronic heart failure should undergo moderate- to vigorous intensity aerobic exercise >3 times a week, 30 minutes per session.
Body weight: there is a positive linear association of BMI with all-cause mortality (4). Prevalence of obesity is significantly increased, especially in young adults. Weight reduction is associated with positive effects on dyslipidaemia, blood pressure, insulin sensitivity and endothelial function, which may lead to reduction of CVD. 
Hypertension is established major risk factor for CHD, heart failure, cerebrovascular disease, PAD, renal failure, atrial fibrillation, dementia and reduce cognitive function. Hypertension should be aggressively treated based on the latest ESC Hypertension and CV prevention guidelines. (1,7)
The decision to start antihypertensive treatment depends on BP level and total cardiovascular risk. In patients with grade 1 or 2 hypertension and moderate total cardiovascular risk, drug treatment may be delayed for several weeks, and in grade 1 hypertension without other risk factors, for several months using only lifestyle measures.
Drug treatment is recommended promptly in patients with grade 3 hypertension, as well as in patients with grade 1 or 2 hypertension who are at high or very high total cardiovascular risk. Systolic blood pressure should be lowered to <140/90 mmHg in all hypertensive patients. Lifestyle measures such as weight control, physical activity, alcohol moderation, sodium restriction, and increased consumption of fruits, vegetables, and low-fat dairy products are recommended in all patients with hypertension and in individuals with high normal blood pressure.
A large number of randomised studies of antihypertensive therapy, both those comparing active treatment vs. placebo, and those comparing drug treatment based on different compounds, confirm that: (I) the main benefits of antihypertensive treatment are due to lowering of BP per se, and are largely independent of the used drugs; and (II) thiazide and thiazide-like diuretics (chlorthalidone and indapamide), betablockers, calcium antagonists, ACE inhibitors, and angiotensin receptor antagonists can adequately lower BP, and significantly reduce risk of cardiovascular morbidity and mortality (8). These drugs are thus all recommended for initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination. The latest meta-analysis of 147 randomised trials reports only a slight inferiority of beta-blockers in preventing stroke (17% reduction vs. 29% reduction with other drugs) but a similar effect to other agents in preventing coronary events and heart failure, and higher efficacy than other drugs in patients with a previous coronary event (8).
Combination treatment is needed to control BP in most patients. Beta-blocker/diuretic combination favors the development of diabetes and should be avoided unless required for other reasons. The combination of an ACE inhibitor and an angiotensin receptor blocker is associated with a consistent increase in serious side effects (9). Treatment with BP-lowering drugs should be continued or initiated also in octogenarians, starting with monotherapy and adding a second drug if needed, based on Hypertension in the Very Elderly Trial (HYVET) (10). Generally, antihypertensive therapy should be maintained indefinitely. 

III - Type 2 diabetes and dyslipidaemia 

Cardiovascular disease increased the rate of all-cause death nearly three-fold and the rate of cardiovascular death nearly five-fold in subjects with diabetes (11). Diabetes is considered coronary artery disease equivalent and diabetic patients are high risk patient’s. Diabetics usually have multiple risk factors and not to forget increased prevalence of subclinical atherosclerosis and silent myocardial ischemia (12). Diabetic patients need close monitoring, intensive control of all risk factors, and early screening of coronary artery disease. 
Recommendations for risk factors treatment in patients with diabetes mellitus type 2: 1) Target HbA1C for prevention of CVD in diabetic patients <7% is recommended 2) Statins are recommended for reduction of CVD 3) Multiple antihypertensive drugs are usually required to reach the target blood pressure <130/80mmHg. Regarding diabetes mellitus, the BP target for patients with was <140/80 mmhg in the 2012 Joint European prevention guidelines and is now
<140/85 mmHg in the 2013 ESH/ESC guidelines on the management of hypertension 4) An ACE inhibitor or angiotensin receptor antagonist should always be included because of the evidence of superior protective effects against initiation or progression of nephropathy 5) Hypoglycemia and excessive weight gain must be avoided 6) Target LDL cholesterol is <2.5mmol/ and total cholesterol <4.5mmol/l for patient without known CVD 7) LDL cholesterol <1.8 mmol/l or at least a 50% reduction from baseline in patients with established CVD and in very-high risk patients with established CVD and high risk patients without known CVD 9) Antiplatelet therapy with aspirin is not recommended for diabetics who do not have evidence of CVD.
Increased plasma cholesterol and LDL cholesterol are among the main risk factors for CVD. Hypertriglyceridaemia and low HDL cholesterol are independent CVD risk factors. 
Before treatment begins, we should always exclude the causes of secondary dyslipidaemia, because often treatment of underlying disease improves dispilidaemia. Treatment strategy of dyslipidaemia depends on the patient risk and baseline lipid fractions values. All patients should have life style changes. Primary target of dyslipidaemia treatment is LDL cholesterol value for each risk category patients. HDL cholesterol is recommended to be used for risk estimation, but not as a target for treatment. Total plasma cholesterol should be <4,5mmol/L and LDL cholesterol <3 mmol/L in individuals with low or moderate risk. LDL cholesterol goal <2.5mmol/l is recommended in high risk patients. In patients with very high risk or known CVD, LDL value should be <1.8mmol/l or at least a 50% reduction from baseline. Patients with acute coronary syndrome need high dose statin therapy started during hospitalization. In patients with renal failure statin and LDL cholesterol target should be adopted to the degree of renal failure.

IV - Combinations and Antithrombotics

Statins are cornerstone drugs for dyslipidaemia treatment. They reduce CV morbidity and mortality and need for coronary artery interventions (13). Patients with dyslipidaemia, often need combination treatment in order to reach treatment targets. Combinations of a statin and a bile acid sequestrant or ezetimibe can be used for greater reduction of LDL cholesterol. Statin and niacin increase HDL cholesterol and decrease triglycerides better than either of these drugs alone. Nevertheless the results from recent trials regarding effects on hard endpoints are disappointing. Statins should be used in the highest tolerable doses to reach target LDL cholesterol levels before combination therapy is used. Fibrates, particularly fenofibrate, may be useful for decreasing high triglyceride and increasing low HDL cholesterol, and further lowering of LDL cholesterol when applied together with a statin. Combination of gemfibrozil with statins should be avoided. 
A - Antiplatelet therapy in individuals without overt cardiovascular disease.
Primary prevention in individuals without established cardiovascular disease was investigated using long-term aspirin vs. control in a systematic review of six trials including 95,000 individuals (14). Risk of vascular mortality was not altered by treatment with aspirin. The CHARISMA trial, which tested clopidogrel vs. aspirin in individuals with multiple risk factors, found no significant clinical benefit in this population (15). Aspirin or clopidogrel are not recommended in individuals without CVD due to increased risk of major bleeding.
B - Antiplatelet therapy in individuals with overt cardiovascular or cerebrovascular disease. 
In the setting of acute coronary syndromes and for the next 12 months dual antiplatelet therapy with P2Y12 inhibitor (ticagrelol or prasugrel) added to aspirin is recommended unless contraindicated due to intolerance or excessive risk of bleeding.
In patients who cannot receive ticagrelolor or prasugrel Clopidogrel (600mg loading dose, 75mg daily dose) is recommended.
After 12 months following myocardial infarction, aspirin is recommended for secondary prevention
In patients with non-cardioembolic transient ischemic attack or ischemic stroke, secondary prevention with either dipyridamole plus aspirin or clopidogrel is recommended. In those patients anticoagulation is not superior to aspirin and is not recommended.

Conclusions

In the era of limited resources of the health care system, the practice of evidence based medicine and assessment of cost/effectiveness of given strategy or treatment have a crucial role in cardiovascular prevention. Cardiovascular prevention is cost/effective, since it reduce CV event by early actions before CV complications occurs. The cardiologists should implement the latest evidence based treatments and help the patient’s comply with the recommendations aimed to reach treatment goals. We have to act continuously not forgetting to work on patient compliance and medication adherence. The higher the level of evidence based care the greater the impact of prevention on cardiovascular events.