Risk factor
OR (CI 99 %)
PAR (99 % CI)
Apo-B/ApoA-1
3.25 (2.81–3.76)
49.2 (43.8–54.5)
Smoking
2.87 (2.58–3.19)
35.7 (32.5–39.1)
Diabetes
2.37 (2.07–2.71)
9.9 (8.5–11.5)
Hypertension
1.91 (1.74–2.10)
17.9 (15.7–20.4)
Abdominal obesity
1.62 (1.45–180)
20.1 (15.3–26.0)
Psychosocial stress
2.67 (2.21–3.22)
32.5 (25.1–40.8)
Daily intake of vegetables and fruits
0.7 (0.62–0.79)
13.7 (9.9–18.6)
Physical activity
0.86 (0.76–0.97)
12.2 (5.5–25.1)
Alcohol consumption
0.91 (0.82–1.02)
6.7 (2.0–20.2)
All combined
129.2 (90.2–185.0)
90.4 (88.1–92.4)
Another important finding of the INTERHEART study was the importance of family history as a risk factor for myocardial infarction (MI). After statistical analysis, its risk factor status was confirmed, with an OR of 1.45 (1.31–1.60). However, the PAR increased only slightly, from 90.4 to 91.4 %, after adding family history to the remaining nine factors evaluated. These findings indicate that most of the risk attributable to family history is associated with other risk factors evaluated.
With a proposal similar to INTERHEART, the INTERSTROKE study is underway and aims at assessing risk factors and their weight in the incidence of ischemic and hemorrhagic stroke. This international case–control study will also evaluate patients from all continents and ethnic groups. The patients are selected at the time of their first stroke and are compared with controls. The INTERSTROKE study [7] has already evaluated 3000 affected patients and 3000 controls, and its preliminary results (Phase 1) showed a risk factor profile similar to that reported for myocardial infarction in the INTERHEART study. Hypertension was the most important risk factor for both stroke subtypes, with a more prominent effect on hemorrhagic stroke. When associated with active smoking, abdominal obesity, diet, and sedentary behavior, the PAR reached 80 % of the overall risk of stroke. The analysis of these five risk factors together with the effects of diabetes, alcohol consumption, psychosocial factors, cardiac causes, and the Apo-B/Apo A1 ratio yielded a list of 10 risk factors, which accounted for 90.3 % of the PAR. Diets with greater consumption of fish and fruits (components of the Mediterranean diet) and physical activity were protective factors. The interaction between alcohol consumption and risk of stroke in INTERSTROKE was complex, suggesting a J-curve relationship for ischemic stroke and a gradual increase of the risk for hemorrhagic stroke as alcohol consumption increased. The risk factors with significant associations with stroke and their respective PAR values are shown in Table 2.
Risk factor | PAR (99 % CI) | |
|---|---|---|
Hypertension | 34.6 % (30.4–39.1) | |
Smoking | 18.9 % (15.3–23.1) | |
Abdominal obesity | 26.5 % (18.8–36.0) | |
Diet (risk score) | 18.8 % (11.2–29.7) | |
Physical activity | 28.5 % (14.5–48.5) | |
Diabetes | 5.0 % (2.6–9.5) | |
Alcohol consumption | 3.8 % (0.9–14.4) | |
Psychosocial stress | 4.6 % (2.1–9.6) | |
Depression | 5.2 % (2.7–9.8) | |
Cardiac causes | 6.7 % (4.8–9.1) | |
Apo B/Apo-A1 | 24.9 % (15.7–37.1) | |
Available Evidence for Primary Prevention
Evaluating the efficacy of preventive measures in apparently healthy individuals is not an easy task, considering that the period elapsed until the development of diseases can be very long. Determining the efficiency of these measures is also difficult because the savings resulting from primary prevention are achieved only in the long term. Therefore, the cost-effectiveness of preventive measures is often determined based on mathematical and statistical models [8].
Lifestyle Changes
Lifestyle changes consist primarily of the control of tobacco and obesity, regular physical activity, and proper diet and have a significant impact on the primary prevention of CVD in a cost-effective manner. The Quality Adjusted Life Years (QALY) indicator is an important tool for the quantification of the impact of a disease or intervention because it combines quantity and quality of life in a single score. Eriksson et al. [9] showed that a lifestyle intervention program based on physical activity and dietary guidance had a cost ranging from USD 1668 to USD 4813 per QALY, a value compatible with a cost-effective measure. A prospective cohort study with 43,685 men and 71,243 women [10] demonstrated that a low-risk lifestyle involving an adequate diet, body mass index (BMI) < 25 kg/m2, no smoking, regular physical activity, and moderate alcohol consumption can reduce the risk of stroke, especially ischemic. In the U.S., between 1985 and 2003, there was a linear and independent relationship between total expenditure on government programs for tobacco control and the decrease in smoking prevalence [11].
Pharmacological Treatment
The effective treatment of diabetes can decrease the number of macrovascular outcomes, according to a meta-analysis that combined the results of the ACCORD, ADVANCE, UKPDS, and VADT studies [12]. A total of 27,049 patients were evaluated, and the results indicated that the risk of myocardial infarction decreased by 15 % (hazard ratio [HR] 0.85, 95 % confidence interval [CI] 0.76–0.94) in the intensive glycemic control group. With regard to the role of statins in the primary prevention of cardiovascular disease, a recent meta-analysis of the Cholesterol Treatment Trialists’ (CTT) collaboration [13] involving 27 clinical trials demonstrated that the use of these drugs could reduce disease outcomes in patients with low estimated risk of adverse events (<10 % in five years). This study reported decreases in the number of major coronary events, stroke, need for revascularization, and major vascular events regardless of the presence of previously diagnosed vascular disease. The use of statins as recommended by current guidelines would cost USD 42,000 per QALY, considering the cost of USD 2.11 per tablet (this value is above the market), which is also a cost-effective strategy [8]. The emerging concept of the polypill can also have important future implications in public health policies. A mathematical analysis of the TIPS study, which evaluated the control of blood pressure, lipid level, heart rate, and antiplatelet effect of aspirin in patients with no history of cardiovascular disease (CVD) with at least one risk factor, reported that the use of polypills could potentially decrease the rate of CVD by 62 % and of stroke by 48 % [14]. Subsequently, Bautista et al. [15] reported that the strategy of the TIPS study is cost-effective in Latin American countries, even among those countries with lower per capita incomes.
Global Proposal for Cardiovascular Prevention
Despite the available knowledge on the impact of cardiovascular risk factors and on the existence of effective primary prevention strategies, the adoption of healthy habits by the population is still very low. An evaluation of 153,996 participants of the Prospective Urban Rural Epidemiology (PURE) study [16] living in urban and rural communities in 17 countries from all continents showed that tobacco use, physical inactivity, and improper diet were highly prevalent, even among individuals who had a previous diagnosis of coronary disease or stroke. In general, the prevalence of a healthy lifestyle was correlated with the patients’ level of education and with income per capita in the countries evaluated and reached levels as low as 4.3 % when the three habits were adopted simultaneously.
After recognizing the political and cultural difficulties for the implementation of the changes necessary to reduce the impact of CVD, the World Health Organization (WHO), during its 66th World Health Assembly in Geneva (May 2012), set as a global target a 25 % reduction in premature mortality from non-communicable diseases by 2025. This resolution included the control of CVD, cancer, diabetes, and chronic respiratory diseases [17]. Based on this resolution, the World Heart Federation (WHF) determined as its primary focus a 25 % reduction in premature mortality from CVD only. For this purpose, cardiologists and healthcare professionals were urged to promote evidence-based good practices for secondary prevention and treatment of cardiac and cerebrovascular diseases; journalists were invited to disseminate the preventive nature of these diseases and to influence state policies; and emerging leaders were encouraged to guide the global agenda on CVD, to promote the adoption of best practices, to guide state policies, and to mediate the responses of health systems.
The means to achieve this audacious goal involved a focus on the main factors with high PAR values, as illustrated in Fig. 1, and consisted of actions that would promote healthy habits and ensure access to healthcare and adequate treatment of hypertension and, specially, of diabetes.
The general principles of the global action proposed are: [18]
Life-course approach;
Empowerment of individuals and communities;
Evidence-based strategies;
Universal healthcare coverage;
Management of real, perceived or potential conflicts of interest;
Protection of human rights;
Equity-based approach;
National action and international cooperation and solidarity; and
Multisectoral actions.
With regard to financial matters, according to estimates, the cost of action would be considerably outweighed by the cost of inaction. The total costs of implementing the measures proposed in relation to the current spending on health are approximately 4 % in low-income countries, 2 % in middle-income countries, and less than 1 % in the richest countries. The estimated spending between 2013 and 2020 is USD 940.2 million, whereas the cumulative cost of non-communicable diseases without proper management would reach USD 47 trillion (75 % of the global gross domestic product [GDP] in 2010). Therefore, spending should be considered as an investment for all countries. One possible source of revenue is the deduction of taxes from products that are harmful to health, including alcohol and tobacco, a strategy that has already been implemented in Jamaica and Thailand [19].
The strategies planned for tobacco control, promotion of a healthy diet, promotion of physical activity, and reduction of alcohol abuse, according to the political statement made in the 66th World Health Assembly, are detailed below [18].
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