Cardiovascular Diseases

Genetic Susceptibility, Environmental Factors and their Interaction

Nikolaos Papageorgiou

• Verlag: Academic Press
• Jahr: 2016
• ISBN:
  9780128033135
• Thema: Ciencias biológicas
• Thema: Genética y genómica

Cardiovascular Diseases: Genetic Susceptibility, Environmental Factors and Their Interaction covers the special heritability characteristics and identifying genetic and environmental contributions to cardiovascular health. This important reference provides an overview of the genetic basis of cardiovascular disease and its risk factors.

Included are important topics, ranging from lifestyle choices, risk factors, and exposure, to pollutants and chemicals. Also covered are the influences of Mendelian traits and familial aggregation and the interactions and interrelationships between genetics and environmental factors which, when compared, provide a sound understanding of the interplay between inherited and acquired risk factors.

The book provides a much needed reference for this rapidly growing field of study. By combining the latest research within the structured chapters of this reference, a better understanding of genetic and environmental contribution to cardiovascular disease is found, helping to substantiate further investigations in the field and design prevention and treatment strategies.

• Provides an overview of the genetic basis of cardiovascular disease and its risk factors
• Reviews several large population-based studies which indicate that exposure to several environmental factors may increase CVD morbidity and mortality, exploring the plausibility of this association by data from animal studies
• Reflects on future studies to help understanding the role of genes and environmental factors in the development and progression of cardiovascular disease

Chapter 1

Summary

N. Papageorgiou¹,  and D. Tousoulis^2     1St. Bartholomew’s Hospital, London, United Kingdom     ²Athens University Medical School, Athens, Greece

Abstract

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in modern societies and encompasses a range of human pathology. It is highly suspected that CVD is strongly related to genetic and environmental factors, and studies have demonstrated that there is an interaction between genetic and environment factors that can lead to cardiovascular disease.

Keywords

Cardiovascular; Environmental; Factors; Genetic; Interaction; Medicine; Susceptibility; Translational

 

Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in modern societies and encompasses a range of human pathology. It is highly suspected that CVD is strongly related to genetic and environmental factors, while studies have demonstrated that there is an interaction between genetic and environment factors that can lead to CVD.

In this book, we aim to review the current knowledge on this topic:

Zaromitidou et al. discuss thoroughly the role of atherosclerosis as well as the role of genetics in CVD, providing related mechanistic links. Further to this, Chandrasekhar et al. review the current data on the impact of genetic variations on antiplatelet therapy, as well as the potential role of genotyping in prescription of antiplatelet therapies in acute coronary syndromes. In addition, MacAloon et al. examine the current cardiovascular epidemiology and perform specific analyses on fatal and nonfatal CVD burden. They also examine risk factor exposure and prevalence to determine explanations for the current pattern of CVD. Specific CVD categories and conditions are also examined to elucidate a more definitive analysis of global CVD determinants. Moreover, Chiesa et al. review the current evidence surrounding the impact of lifestyle choices on cardiovascular risk factors and disease, and they discuss the beneficial effects of modifying these behaviors with regard to morbidity and mortality. Hatzis et al. summarize the thus-far-acquired knowledge on the main pollutants and present the basic mechanisms that mediate their actions on the vasculature.

Briasoulis et al. acknowledge the contribution of candidate gene studies to complex CVDs such as acute coronary syndromes, and the fact that the clinical impact and the pathophysiological implications of polymorphisms are elusive. On top of these data, Swerdlow et al. discuss the different relationships that a risk factor can have with disease and the role of genetic studies in causal inference, and they evaluate the insights provided by genetics into the contribution of some prominent risk factors to CVD pathogenesis.

Furthermore, Dumitru et al. provide a few examples of genetic susceptibility in biochemical and physiological traits of CVD. They also examine the opportunities provided by pharmacogenomics for future improvements in treatment of CVD. Finally, Norrington et al. introduce key concepts in gene–environment interactions in CVD. The expounding importance of gene–environment interactions in understanding the missing heritability of multifactorial CVDs is highlighted as well as the fundamental concepts of statistical and biological interactions.

The available data are promising, and there are still ongoing studies aiming to evaluate the interactions between genetics and environmental factors in CVD. We hope that the information and data provided will be interesting for the readers of the book and will stimulate further research on the topic.

Chapter 2

Atherosclerosis and Coronary Artery Disease

From Basics to Genetics

M. Zaromitidou, G. Siasos, N. Papageorgiou, E. Oikonomou, and D. Tousoulis Athens University Medical School, Athens, Greece

Abstract

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.

Keywords

Atherosclerosis; Cardiovascular disease; Coronary artery disease; Endothelium; Genetics; Inflammation

Introduction

Cardiovascular disease is the leading global cause of death. According to the World Health Organization, 17.3 million deaths resulted from cardiovascular disease worldwide in 2008, and that number is expected to reach 23.3 million by 2030. The underlying pathology of cardiovascular disease is atherosclerosis and, depending on the artery affected, can manifest as CAD or as cerebrovascular or peripheral disease. Coronary artery disease (CAD) is responsible for 7.3 million deaths and is the second cause of death in people under the age of 59. It is also noteworthy that CAD is listed among the first causes for years of life lost due to premature death or disability, and thus has important social and economic impact. Low- and middle-income countries exhibit a continuous increase in the prevalence of CAD in contrast to developed countries. This discrepancy is attributed to the ineffective primary and secondary prevention measures in addition to poor healthcare systems in the low- and middle-income countries [1].

The mechanisms of atherosclerosis have gained increasing attention over recent decades. Many questions still remain concerning the heterogeneity that atherosclerosis displays in time (when?), in the areas affected (where?), in the factors triggering the initiation (how?), and in defining the natural history and evolution of the disease (why?). Atherosclerosis is a chronic systematic disease involving large and medium-sized arteries that initiates early in life [2]. As it progresses, the structure of normal arteries is modified, and atherosclerotic plaques are formed with consequent narrowing or dilation of the vessel. Atherosclerosis is a systematic disease with local manifestations, but the factors determining the preferential involvement of a vascular region over another (ie, coronary or carotid artery) as well as the development of atherosclerotic lesions in certain sites of a specific artery (eg, branches, curvatures, and proximal areas of left anterior descending) are unclear. In addition, regardless of tremendous research efforts, sparse data are available illuminating the factors responsible for the transition of a stable atherosclerotic plaque to a vulnerable plaque that can cause the acute complications of atherosclerosis (eg, myocardial infarction (MI) in CAD). Diversity also exists in the biological procedures and their clinical manifestations following rupture or erosion of unstable plaques (clinically silent MI, unstable angina, and MI with or without ST elevation).

The biggest question to be answered is why the human arteries are vulnerable to atherosclerotic changes. As most communicable diseases are now successfully treated and average life expectancy has increased, cardiovascular disease burden emerges as one of the most important health issues. It was some decades ago that the Framingham Heart Study provided valuable data regarding the primary prevention of atherosclerotic cardiovascular disease and established the cardiovascular risk factor as a new term. The identification of several risk factors associated with modern lifestyle such as hyperlipidemia, smoking, hypertension, obesity, diabetes mellitus, lack of exercise, anxiety, and depression supports the notion that atherosclerosis is a disease of urbanization [3]. However, well-known risk factors such as older age, family history of cardiovascular disease, male sex, and genetic abnormalities (familial hypercholesterolemia) indicate a genetic contribution to atherosclerosis. The report of atherosclerotic findings in mummies from populations of disparate regions with differences in dietary habits and certainly differences in dietary and lifestyle patterns compared to the present time suggests that human vessels are susceptible to atherosclerotic alterations regardless of the current environmental risk factors. Moreover, these observations underline the ongoing need for novel risk factors [4]. Therefore, both genetic and environmental factors are implicated in the pathogenesis of atherosclerosis, whereas their interaction may account for the heterogeneity that atherosclerosis displays.

Normal Artery Structures

The normal artery wall comprises three layers: the tunica intima, the tunica media, and the tunica adventitia.

• The tunica intima consists of the endothelium, connective tissue (collagen, laminin, fibronectin, and other extracellular matrix molecules), and a basal layer of elastic tissue called internal elastic lamina that separates the tunica intima from tunica media. Endothelium is a thin monolayer of cells that serves as the contact surface with blood. Due to its strategic location, the endothelium has emerged as the main regulator of vascular homeostasis with its structural and functional properties altered in response to...