It is widely accepted that the classic risk factors for atherosclerosis only partly explain the incidence of coronary artery disease and the development of acute coronary syndromes. Therefore, genetic factors that vary among human populations seem to be involved in the clinical manifestations of such patients. Substantial data suggest that a significant proportion of genetic polymorphisms involved in endothelial function, inflammation, lipid metabolism, and thrombosis/fibrinolysis are often present in patients with acute coronary syndromes. Despite the well-established contribution of candidate gene studies to complex cardiovascular diseases such as acute coronary syndromes, the clinical impact and the pathophysiological implications of polymorphisms are elusive. With the evolution of genomic technologies, the necessary genetic tools may be soon available to introduce novel diagnostic and therapeutic strategies that will alter cardiovascular morbidity and mortality.
Cardiovascular disease encompasses a range of human pathology that is characteristic of so-called "complex" diseases. Complex diseases are caused not by a single pathogen or highly penetrant genetic mutation but by the concerted effects of a large number of risk factors. Risk factors can include perturbations of normal physiology, such as dyslipidemia or hypertension, behaviors such as smoking, and environmental influences such as airborne pollutants. Each of these is associated with differences in cardiovascular disease risk. Only a subset so far, however, are thought of as causal mediators, responsible for driving the etiology of the disease, while the remainder are merely deemed to be markers of risk, lacking a causal role. Genetic studies of cardiovascular disease have begun to suggest novel risk factors for cardiovascular disease and to allow new ways of investigating whether a given risk factor has a causal role in the disease. In this chapter, we discuss the different relationships a risk factor can have with disease, the role of genetic studies in causal inference, and evaluate the insights provided by genetics into the contribution of some prominent risk factors to cardiovascular disease pathogenesis.
Cardiovascular disease (CVD) is one of the leading global causes of morbidity and mortality. Although certain risk factors associated with CVD progression—such as age, gender, and family history—are nonmodifiable, the majority of factors influencing CVD risk can be attributed to an individual's lifestyle choices and, as such, have the potential to be improved through particular lifestyle modifications. These behaviors are traditionally found in affluent developed countries and consist of unhealthy dietary intake, low levels of physical activity, and tobacco and alcohol consumption. These lifestyle choices act both in isolation and in synergy to increase multiple cardiovascular (CV) risk factors, which in turn have the potential to interact with each other to further elevate risk. This chapter will review the current evidence surrounding the impact of these lifestyle choices on CV risk factors and disease, and will discuss the beneficial effects of modifying these behaviors with regard to morbidity and mortality.
This chapter introduces key concepts in gene–environment interaction in cardiovascular disease. The expounding importance of gene–environment interaction in understanding the missing heritability of multifactorial cardiovascular diseases is highlighted as well as the fundamental concepts of statistical and biological interaction. Moreover, a growing body of evidence has suggested an interaction between genotype (eg, APOE, ADH1-3, and CYP1A2), dietary factors (eg, alcohol, caffeine, and fruit intake), and the risk of coronary heart disease. Of note, the role of epigenetics as a mechanism of environmental pollutant–driven cardiovascular disease and the emerging role of pharmacogenetics have been recently recognized. Other genetic mechanisms such as single nucleotide polymorphisms in maternal folate metabolism and congenital heart disease will also be explored in this chapter.
Current evidence suggests that environmental pollution plays a key role in the initiation and the evolution of cardiovascular disease. A plethora of environmental substances and products as well as natural products are implicated in the cascade that promotes the atherosclerotic process. The main and well-studied representatives are air pollutants as well as heavy metals. The aim of this chapter is to summarize the knowledge thus far acquired on the main pollutants as well as to present the basic mechanisms that mediate their activities on the vasculature.
The pattern and global burden of disease has evolved considerably over the last two decades from primarily communicable, maternal, and perinatal causes to noncommunicable disease (NCD). Cardiovascular disease (CVD) has become the single most important and largest cause of NCD deaths worldwide, at over 50%. The World Health Organization (WHO) estimates that 17.6 million people died of CVD worldwide in 2012. Proportionally this accounts for an estimated 31.3% of global mortality, with ischemic heart disease (IHD) accounting for 7.4 million deaths, 13.2%. IHD was also the greatest single cause of death in 2000, accounting for an estimated 6.0 million deaths. The global burden of CVD falls, principally, on the lower- and middle-income countries, accounting for over 80% of CVD deaths. Individual populations face differing health challenges, and each specific population has unique health burdens, however, CVD continues to remain one of the greatest health challenges worldwide.
Dual antiplatelet therapy with aspirin and a P2Y12 receptor antagonist is standard of care in acute coronary syndrome and is recommended for a period of 12 months regardless of invasive revascularization. The antiplatelet action of these agents is governed by levels of active plasma metabolites, which may be influenced by genetic variations. Recently genotyping has gained considerable attention to identify patients who may demonstrate poor platelet responsiveness, as a potential method to improve long-term outcomes. However whether or not systematic genotyping will prove to be advantageous and cost-effective is the subject of on-going studies. This chapter discusses the current data on the impact of genetic variations with antiplatelet therapy, as well as the potential role of genotyping in prescription of antiplatelet therapies in acute coronary syndrome.
The Human Genome Project has revolutionized medicine. Since its completion in 2003, the number of identified genetic mutations causing various disorders, including those of the cardiovascular system, has grown rapidly. Among these are the relatively common hypertrophic cardiomyopathy, connective tissue disorders such as Marfan syndrome or Loeys–Dietz syndrome, cardiac arrhythmia disorders including long-QT syndrome and Brugada syndrome, and an increasing number of defects predisposing to atherosclerosis, which itself may lead to stroke, myocardial infarction, and premature death. Genetic mutations leading to specific biochemical and physiological traits may be directly causative for certain disorders, or they may contribute to their pathogenesis. Our knowledge of pathological and biochemical changes brought on by genetic mutations is growing increasingly faster and will continue to grow in the coming years.
Despite the tremendous progress in primary and secondary prevention, coronary artery disease (CAD) is unfortunately among the leading causes of death globally. Atherosclerosis, the underlying pathology of CAD, is the result of multiple complex mechanisms, many of which still remain unclear. In order to prevent or treat atherosclerotic complications, it is imperative to clarify and comprehend the mechanisms involved in the pathogenesis. The central role of lipoproteins and inflammation in atherosclerosis has been validated in many studies. Genome-wide association studies identified the first genetic loci associated with CAD, confirming the detrimental role of lipoproteins and underscoring the presence of unknown mechanisms. Further deciphering of the molecular and gene mechanisms that lead to atherosclerosis provided novel therapeutic targets such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and mipomersen.
Cardiovascular diseases (CVDs) continue to be the leading cause of health problems around the world. Because of its unique properties, reactive oxygen species (ROS)-based nanotechnology offers novel solutions to the diagnosis and treatment of CVDs. In order to identify and further promote the development of ROS-based nanotechnology in CVDs, we here provide a bibliometric analysis. 701 eligible articles about the ROS-based nanotechnology for CVD up to May 26th, 2022, were taken from the Web of Science Core Collection database. The VOSviewer was used to analyze annual publications, countries/institutions, funding agencies, journals and research category, and the research hotspots. From the publication of the first article in 2005 to 2021, the output and the number of citations of articles are on the rise. Based on the bibliometric analysis, we found that the current research focuses on the correlation between diagnosis (sensors and), treatment (oxidative stress, inflammation, and drug delivery) and safety (toxicity). Since 2019, research on nanomedicine and drug delivery has become a hotspot. So, more research in chemistry, materials, biology, and medicine is required to further develop and construct ROS-based nanomaterials.
