The heart organ is a powerful pump that circulates blood, nutrients and oxygen throughout the body and, surprisingly, is the first organ to form during embryonic development. In Greek medicine, it was considered the most important organ, and today, the fact that heart disease remains the leading cause of death worldwide invites us to try to better understand the molecular, genetic and environmental basis of cardiovascular development and disease. 
The circulatory system, or cardiovascular system, consists of the heart and a closed system of blood vessels, consisting of arteries, veins and capillaries. As a curiosity, it is worth noting that if all the blood vessels of a person were joined together, they would measure about 100,000 kilometers, that is, more than twice the measurement of the earth’s circumference. Its main function is to transport nutrients and oxygen-rich blood to all organs of the body and to carry deoxygenated blood back to the lungs.
This vital role of the cardiovascular system depends on the continuous and controlled movement of blood through the thousands of kilometers of capillaries that run through every tissue and reach every cell in the body. It is in the microscopic capillaries that the blood performs its final transport function. Nutrients and other essential materials pass from the capillary blood into the fluids surrounding the cells, while waste products are removed. 
Cardiovascular disease figures
Cardiovascular diseases are one of the leading causes of death in Europe, where they are responsible for approximately 4 million deaths annually, about 45% of all deaths. Specifically, ischemic heart disease and cerebrovascular diseases, the two main groups of cardiovascular diseases, are responsible for about 2 million and 1 million deaths, respectively. 
According to the European Society of Cardiology (ESC), age-standardized data for 2015 showed that nearly one in four people in ESC member countries had elevated blood pressure (Figure 1). Systolic blood pressure was higher in men than in women and in middle-income countries than in high-income countries. In almost all countries, the prevalence of elevated blood pressure has trended downward over the past 35 years, but current rates of decline do not appear sufficient to meet the WHO noncommunicable disease target for 2025. 
Figure 1. Age-standardized incidence of cardiovascular disease in European Society of Cardiology member countries (2017). 
In a study by the European Heart Network, it was estimated that cardiovascular disease (CVD) cost the European Union economy €210 billion in 2015 alone, of which 53% (€111 billion) was due to healthcare costs; 26% (€54 billion) was due to productivity losses; and 21% (€45 billion) was due to informal care of people with CVD. The study showed that the economic burden of CVD varies considerably, with direct health costs per capita ranging from €48 in Bulgaria to €365 in Finland. 
Reducing cardiovascular disease (CVD) morbidity and mortality is the goal of clinical and population-based preventive strategies. As CVD is multifactorial, it is necessary to control and act on several different risk factors at the same time. Multifactorial or complex diseases are those that are not limited to any single gene inheritance pattern and in most cases are associated with the effects of multiple genes together with the effects of environmental factors.
CVD risk stratification is important because there are individuals who do not yet have overt disease, but may develop it. Total CVD risk means that an individual is likely to develop a fatal cardiovascular event during a given period of time. To help diagnose and monitor individuals who have a higher risk of developing CVD, follow-up models have been developed and are currently used in Europe in the form of systemic coronary risk estimation (SCORE) charts (Figure 2).
Figure 2. a) SCORE chart: 10-year risk of fatal cardiovascular disease (CVD) in countries at high risk of CVD. b) SCORE chart: 10-year risk of fatal cardiovascular disease (CVD) in countries at low risk of CVD.
Risk factors for the development of cardiovascular disease.
Today’s risk behaviors become tomorrow’s risk factors, and risk factors become tomorrow’s cardiovascular diseases. In this context, attempts have been made to develop health promotion and disease prevention programs based on the global scientific discoveries that have occurred in recent decades.  The base strategy used by these health campaigns is mainly focused on avoiding or reducing the factors that increase the risk of developing CVD. These include:
→ Blood pressure. Arterial hypertension (HT) is one of the most important preventable factors of premature mortality in the world. It is also the most important independent risk factor for CVD. In most developed countries, more than 30% of adults have hypertension. Therefore, primary prevention should start as early as possible. 
→ Cholesterol. Most circulating cholesterol is in the form of LDL (low density lipoprotein) cholesterol, which is directly associated with CVD risk. High levels of LDL are associated with atherogenic risk, which is defined as the possibility of developing alterations that lead to the appearance of a lipid deposit in the artery wall. This lipid deposition can lead to the development of calcification plaque, and thus to loss of arterial elasticity or atherosclerosis. Thus, hypercholesterolemia is an indicator of increased cardiovascular risk. 
→ Diabetes. Diabetes mellitus (DM) is a group of metabolic disorders whose main characteristic is the presence of elevated blood glucose concentrations. It is estimated that, in 2030, approximately 64 million people in Europe will suffer from type 2 DM. This is worrying because most diabetics die from CVD. People with DM are at high risk and the SCORE table is not applicable to them. Therefore, it is important to modify lifestyle habits, regulate body weight, increase physical activity, and adopt healthy eating habits, to prevent the development of DM and CVD or its progression. 
→ Obesity. The prevalence of obesity in the world is increasing, especially in the more developed countries, and contributes to a significant increase in CVD morbidity. Sedentary lifestyle and poor nutrition habits are the main cause of obesity. There is a linear association between body mass index (BMI), obesity and especially abdominal girth with total mortality. Most important is the prevention of obesity early in life. Education and media influence are important in the prevention of childhood obesity. 
→ Smoking. Cigarette smoking is a dominant risk factor in cardiovascular and noncardiovascular mortality and morbidity. It is estimated that by 2025 there will be 1.6 billion smokers in the world, and that 10 million people per year will die from smoking. For that reason, it is considered the most important risk factor to avoid in preventing the development of CVD. 
→ Genetics. CVD are complex and genetically heterogeneous diseases, resulting from many gene-gene and gene-environment interactions. For this reason, molecular genetics and pharmacogenetics play a key role in the diagnosis, prevention, and treatment of CVD. Genetic testing is commonly used to identify the underlying genetic cause in patients with suspected cardiovascular disease and to determine who in the family has inherited the causal variant and is therefore at risk of developing CVD. 
Protective factors for cardiovascular health
Nearly one third of CVD deaths are considered potentially preventable. The American Heart Association (AHA) has published recommendations that define the ideal state of cardiovascular health. Among them we find:
→ Healthy nutritional habits. A healthy diet is the foundation of CVD prevention. Eating habits influence blood fat and sugar levels, blood pressure, and body weight. Healthy nutrition reduces the risk of other chronic diseases. The Mediterranean diet is considered to meet all healthy nutritional recommendations. It is difficult to isolate the effects of individual nutrients on health benefits, and current research suggests that it is more important to consider the diet as a whole, rather than focusing on specific nutrients. Several dietary approaches have been studied for their effects on CVD. Low-fat diets and high-fat, low-carbohydrate diets are popular and effective for weight loss, but there is insufficient evidence to recommend them for primary prevention of CVD. 
→ Physical activity. Regular physical activity is protective and has many benefits. It has a direct impact on the reduction of already existing vascular lesions and reduces other risk factors (reduces body weight, lipid levels, blood sugar levels, and blood pressure) and thus decreases the incidence of coronary heart disease. Recommendations for physical activity in adults are at least 150 minutes of moderate-intensity aerobic activity or at least 75 minutes of vigorous activity per week. 
Genetics and cardiovascular health
With the advent of resources and technology following the Human Genome Project, there has been a flurry of research directed at genome-wide predisposition markers and pharmacogenetics in complex cardiovascular disorders. Genomic research has shed light on the impact of previously identified genes on the development and progression of cardiovascular disease. In addition, it has uncovered as yet unknown genomic regions that are associated with cardiovascular outcomes. 
The promise of personalized medicine lies in combining this genetic information with other biomarkers to tailor preventive and therapeutic strategies to individual patients for effective treatment, fewer adverse effects, and greater efficiency in preventive care. 
An example of this is myocardial infarction (MI). This disease has been shown to be heritable and is among the leading causes of death and disability worldwide. While most MIs occur in individuals over 65 years of age, 5-10% of new MIs occur in younger patients and these events are associated with substantially higher heritability. Therefore, individuals with a family history of early-onset MI have a promising profile for genetic mapping. 
Specifically, in the melanoma inhibitory activity 3 or MIA3 gene, polymorphisms have been described that are associated with an increased genetic predisposition to develop MI. A polymorphisms is a DNA sequence variation that occurs in a population at a frequency of 1% or higher. 
In addition, many of the risk factors for cardiovascular disease, such as diabetes, elevated LDL cholesterol or obesity also have an important genetic component. In the case of type 2 diabetes, some mutations in genes such as RREB1, TCF19 or VEGFA have been associated with an increased predisposition to develop this disease. 
24Genetics and cardiovascular health
From 24Genetics we provide a solution for preventive care of cardiovascular health, by understanding individual genetic predispositions. In our health report we analyze the main genes and polymorphisms involved in the development of pathologies such as 1S dilated cardiomyopathy, familial hypertrophic cardiomyopathy or myocardial infarction, among many others, to inform about possible genetic predispositions to this type of diseases.
1. Granger, A. & Emambokus, N. Cell Metabolism ♥ Cardiovascular Biology. Cell Metab. 21, 151 (2015).
2. López, E. M. FISIOLOGIA DEL SISTEMA CARDIOVASCULAR. Educ. Física Deporte 6 (1979).
3. Di Girolamo, C. et al. Progress in reducing inequalities in cardiovascular disease mortality in Europe. Heart 106, 40–49 (2020).
4. Timmis, A. et al. European Society of Cardiology: Cardiovascular Disease Statistics 2019. Eur. Heart J. 41, 12–85 (2020).
5. Francula-Zaninovic, S. & Nola, I. A. Management of Measurable Variable Cardiovascular Disease’ Risk Factors. Curr. Cardiol. Rev. 14, 153–163 (2018).
6. Reddy, K. S. Cardiovascular Health. J. Am. Coll. Cardiol. 65, 1026–1028 (2015).
7. Hollander, W. Role of hypertension in atherosclerosis and cardiovascular disease. Am. J. Cardiol. 38, 786–800 (1976).
8. Carson, J. A. S. et al. Dietary Cholesterol and Cardiovascular Risk: A Science Advisory From the American Heart Association. Circulation 141, (2020).
9. Henning, R. J. Type-2 diabetes mellitus and cardiovascular disease. Future Cardiol. 14, 491–509 (2018).
10. Powell-Wiley, T. M. et al. Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation 143, (2021).
11. Ambrose, J. A. & Barua, R. S. The pathophysiology of cigarette smoking and cardiovascular disease. J. Am. Coll. Cardiol. 43, 1731–1737 (2004).
12. Manace, L. C., Godiwala, T. N. & Babyatsky, M. W. Genomics of Cardiovascular Disease: L. C. MANACE ET AL.: SPECIAL FEATURE-GENOMICS OF CARDIOVASCULAR DISEASE. Mt. Sinai J. Med. J. Transl. Pers. Med. 76, 613–623 (2009).
13. Lanier, J. B. Diet and Physical Activity for Cardiovascular Disease Prevention. 93, 6 (2016).
14. Myocardial Infarction Genetics Consortium. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat. Genet. 41, 334–341 (2009).
15. Koch, W. et al. Extended evidence for association between the melanoma inhibitory activity 3 gene and myocardial infarction. Thromb. Haemost. 105, 670–675 (2011).
16. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium et al. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat. Genet. 46, 234–244 (2014).