Cardiovascular disorders are a heterogeneous group of diseases which share common underlying pathological manifestations. Atherosclerosis is a complex phenomenon and itself a result of a combination of pathological processes including inflammation and endothelial damage. Far from a simplistic view that atherosclerosis is lipid driven and predominantly a cholesterol-related disorder, more recently a number of inflammatory cells have been implicated in the process including monocytes [6], macrophages [7], neutrophils [8] and dendritic cells [9], and further exploration of novel chemokines including CCL2 [10], CCL17 and macrophage migration inhibitory factor [10] can yet advance our understanding of the disorder. A better understanding of the role of inflammation in atherosclerosis can in theory lead to the introduction of immunomodulators alongside statins to treat those with difficult-to-control atherogenic dyslipidaemia.

Endothelial dysfunction is characterised by processes which result in attenuated endothelial vasodilatation, either by reducing the bioavailability of nitric oxide or by increasing levels of endothelium-derived vasoconstrictor and prothrombotic factors [11]. Endothelial dysfunction has been described in diabetes mellitus [12–14], hypertension [15, 16], aging [17–19], chronic kidney disease [20] and obesity [21, 22] and contributes to formation of atherosclerotic plaques and vascular stiffness.

Vascular remodelling is an adaptive process in response to long-term changes in the haemodynamic environment that ultimately may contribute to vascular and circulatory disorders. Four main processes have been implicated in remodelling: cell growth, cell death, cell migration and extracellular matrix production or degradation [23]. The specific type of remodelling depends on the disease process necessitating the change within the vasculature. Eutrophic remodelling (rearrangement of the same cellular material around a narrowed lumen resulting in increased media/lumen ratio) has been described in patients with essential hypertension [24] and hypertrophic remodelling (increase in wall thickness or media cross-sectional area and preservation of the lumen diameter) in individuals with diabetes [25–27]. Similarly, obese patients exhibit an increase in media-to-lumen ratio in keeping with hypertrophic remodelling [28], and persistent weight loss following weight-loss surgery regresses these vascular changes [29].

Over the past 10 years, microRNAs have emerged as a rapidly advancing domain offering much promise to enhance our understanding of the pathobiology of CVDs at the molecular and cellular level. MicroRNAs are small noncoding RNAs involved in post-transcriptional gene regulation by binding to mRNA sequences resulting in a reduction of protein expression or leading to mRNA degradation [30]. The potential involvement of microRNAs has been reported in atherosclerosis [31, 32], endothelial cell function [30] and arterial remodelling [33], as well as in disorders such as peripheral arterial disease [34], stroke [35], obesity [36] and aortic disease [37]. A better understanding of the role of microRNAs in cardiovascular disorders will no doubt lead to development of future therapies [38].

Over the years, a variety of techniques have been utilised to study the micro- and macro-circulation at molecular, cellular and tissue level. These include functional assessments of vessel wall and luminal changes using wire and pressure myography, arterial stiffness studies using pulse wave velocity measurements as well as high-resolution ultrasound assessment of endothelial function using flow-mediated dilatation, evaluation of reactive hyperaemia using gauge-strain plethysmography and more recently, pulse amplitude tonometry [39, 40]. One of the most recent developments in the field of cardiovascular investigations is the emergence of retinal artery imaging as a means of assessment and monitoring of arterial disease. The retinal microcirculation offers a noninvasive and easily accessible window to the human microvasculature. Advances in imaging technology using computer-based analysis of retinal photographs allow for reproducible means for quantification of retinal vascular calibre. Changes in retinal vascular calibre are associated with age, ethnicity and genetic factors [41]. Changes such as narrowing of retinal arteriolar calibre, enhanced arteriolar wall reflex and wider venular calibre are associated with the metabolic syndrome [42, 43], waist circumference [44, 45], higher triglyceride levels [45], diabetes and hypertension [44, 46] as well as stroke [47, 48], coronary microvascular disease [49] and coronary artery disease [50]. Retinal microvascular changes can predict subsequent vascular events following ischaemic stroke [51]. These changes are also observed in the paediatric and adolescent population [52–54]. Retinal microvascular signs such as venular dilatation are associated with CKD both in the presence and absence of diabetes, thus reinforcing the link between renal and retinal microvasculature independently of diabetes [55].

Identifying major risk factors for arterial disorders with the aim of developing new therapies and public health strategies to reduce cardiovascular mortality and morbidity has been at the forefront of efforts by major healthcare, academic, pharmaceutical and governmental bodies. However, despite our best efforts, cardiovascular diseases are on the rise, and controlling and treating their risk factors remain a major challenge.

Obesity has emerged as a major global healthcare burden and a symptom of our unhealthy lifestyles. In the most simplistic terms, obesity is a result of the imbalance between calories consumed versus calories expended. The worldwide prevalence of obesity has nearly doubled between 1998 and 2008. Over half a billion adults over 20 were obese in 2008 (10 % of all men and 14 % of all women) [56]. The obesity prevalence tripled from 7 % in lower-middle-income countries to 24 % in upper-middle-income countries. In low- and medium-income countries, there is a positive correlation between socioeconomic status and obesity; however, in the European Union, there seems to be an inverse relationship between education and obesity/BMI [57–60]. These trends most likely reflect the growing awareness of the detrimental effects of obesity on health in the developed countries which should extend to the developing countries in the not-too-distant future and help reduce the mortality rate from 2.8 million deaths each year (2008) as a result of overweight and obesity [1]. In the context of the metabolic syndrome, obesity often coexists with hypertension, diabetes and high cholesterol. There is an intricate interplay between the components of the metabolic syndrome which is evident from both cellular and epidemiological data. For example, those with a raised waist circumference are twice as likely to have high blood pressure [61]. The interplay between adipose tissue and adjacent vasculature has been studied in the context of perivascular adipose tissue and adipokines with vasoactive properties. White adipocytes are the main constituents of perivascular adipose tissue (PVAT) which surrounds a large proportion of blood vessels in the human body and secretes molecules known as adipokines. Healthy PVAT exerts a vasorelaxant effect mediated via a number of potential candidates including adiponectin [62], nitric oxide [63], hydrogen sulphide [64] and methyl palmitate [65]. In obesity, the vasorelaxant effect is not observed thus, in theory, contributing to increased resting tone in peripheral small arteries. Interestingly, weight loss following bariatric (weight loss) surgery restores the PVAT vasorelaxant effect with its potential beneficial effects on resting BP [66]. These recent data are encouraging as they indicate the potential for reversal of a degree of the obesity-induced cardiovascular damage.

Smoking is thought to cause around 10 % of cardiovascular diseases worldwide [1]. Globally, there are more than one billion smokers, and despite a decrease in the use of tobacco products in high-income countries, the total number of smokers is increasing given that 80 % of the world’s smokers live in low- and middle-income countries. Smoking kills 5.4 million people a year and has resulted in 100 million deaths in the twentieth century [67]. Smoking cessation is very effective at reducing mortality, and in those with coronary heart disease, it leads to a 36 % reduction in crude relative risk of mortality [68]. The recent emergence and popularity of E-cigarettes has proven controversial given that they may be a helpful aid to smoking cessation, but the hype around the new products might lead to a renewed interest in nicotine-based products and in some cases serve as an introduction to cigarette smoking. The true effect of E-cigarettes on health and on smoking trends will become apparent in the next decade.

The aging population of the world is another risk factor for cardiovascular disease and one which has no prescribed treatment. The developed countries, and to a certain extent the developing countries, have fallen victim to their own economic success. Improved quality of life, falling birth rates and longer life expectancies have resulted in increasingly old populations in the developed countries. In 2010, at least 20 % of the populations of the more industrialised countries were over the age of 65, and by 2050, one billion people will be over the age of 65 worldwide [69]. Age-related vascular changes have been well documented. These include luminal enlargement with wall thickening, arterial stiffness and endothelial dysfunction. Arterial stiffness is the reduced capability of a blood vessel to dilate and constrict in response to changes in pressure. Both a linear relationship between age and stiffness [70] as well as an accelerated stiffening between ages 50 and 60 have been described [71]. The aetiology of endothelial dysfunction in aging is multifaceted and includes a reduction in endothelial nitric oxide synthase activity leading to a reduction in endothelial vasodilation, as well as a decline in the integrity of the endothelium as a barrier and loss of the ability of endothelial cells to proliferate and migrate after tissue injury [72]. Aging is one CVD risk factor that cannot be curbed; however, new treatment strategies to fight the effects of aging might help alleviate the burden of an increasingly old population.

In 2008, around 40 % of adults had raised blood pressure [73], and it accounts for nearly 13 % of all deaths (7.5 million) worldwide [1]. Hypertension is a major risk factor for ischaemic heart disease (IHD) and haemorrhagic stroke with 54 % of stroke and 47 % of IHD attributable to hypertension. Eighty percent of this burden occurred in low-income and middle-income countries [74]. Moreover, blood pressure levels have been shown to be positively and progressively related to coronary heart disease and stroke [75]. In those older than 50, every increment of 20/10 mmHg results in a doubling of cardiovascular risk, starting as low as 115/75 mmHg [76]. This highlights the importance of effective control of blood pressure which might be addressed using a combination of antihypertensive drugs as well stressing the importance of compliance.

Dyslipidaemia is another major cardiovascular risk factor. In 2008, 39 % of adults had raised total cholesterol and an estimated 2.6 million deaths were attributed to this risk factor alone. In high-income countries, 50 % of the population had raised total cholesterol which is double that of low-income countries, with 2.6 million deaths annually [1]. The Framingham study first reported a link between high cholesterol and increased coronary heart disease in the 1960s [77], and more recently, lipoprotein (a) which is an LDL-like particle has been independently associated with CHD and stroke [78]. Various treatment strategies have aimed to reduce CVD risk in those with dyslipidaemia, but statins have been the most significant players in this field. Recent controversy around statin use has threatened to derail the success of preventing cardiovascular mortality by treating high cholesterol. The authors of a paper published in 2013 by the British Medical Journal [79] had indicated that statin therapy in low-risk individuals does not result in a reduction in all-cause mortality or serious illness whilst conveying an 18 % risk of side effects. The subsequent media reports have no doubt concerned physicians, as sensationalist headlines could potentially affect patient compliance with medication.

Cardiovascular disease is the leading cause of morbidity and mortality in people with diabetes, and diabetes is a significant contributor to cardiovascular risk. In 2001, just under a million deaths were directly caused by diabetes, and nearly 1.5 million deaths from ischaemic heart disease and 700,000 deaths from stroke were attributed to high blood glucose [80]. However, with the emergence of better treatment strategies and patient education, the tide might just be changing. In the past two decades, the difference in CVD complications in people with and without diabetes has narrowed substantially. In 1990, the rates of acute myocardial infarction and stroke were three to four times higher in those with diabetes as compared with the general population; however, by 2010, this difference had been reduced to less than double that of the general population without diabetes [81]. Moreover, since the 1990s, there has been a 3–5 % decline in the rates of acute myocardial infarction, cardiovascular mortality and all-cause mortality in patients with diabetes [82]. This might be a result of earlier detection of diabetes, as well as more effective drugs with fewer side effects and a renewed emphasis on patient education.

Arguably, urbanisation has been the most significant contributor to the growing cardiovascular mortality worldwide. As of 2010, more than half of the world’s population live in cities. The advent of globalisation and urbanisation coupled with the emergence of 21 megacities around the world (>10 million) has led to the realisation that inhabitants of cities are at a greater cardiovascular risk than their rural counterparts simply by the virtue of the fact that their lifestyles have changed beyond recognition. Reduced physical activity, the use of motorised transportation, air pollution, sedentary jobs, stress of commuting to work, increased rates of smoking and readily available ‘junk food’ consisting of high calorie and high salt and sugar foods with low nutritional value, all contribute to increases in blood pressure, obesity and cardiovascular risk in general [69]. Air pollution in particular has been linked with increased incident stroke risk [83], and high residential traffic exposure has been linked with increased blood pressure in a recent comprehensive meta-analysis of European population-based cohorts [84].

Cardiovascular diseases are no different to other disorders in that prevention is better than cure. The World Health Organization ‘best buy’ interventions for treatment and prevention of CVD would cost around 11–13 billion dollars annually which is a significant saving considering that in the next 25 years, the cost of not investing in CVD prevention and treatment is predicted to be as much as $47 trillion worldwide [69]. These ‘best buys’ include protecting people from tobacco smoke and banning smoking in public places, warning about the dangers of tobacco use, enforcing bans on tobacco advertising and sponsorship, raising taxes on tobacco, restricting access to retailed alcohol, enforcing bans on alcohol advertising, raising taxes on alcohol, reducing salt intake and salt content of food, replacing trans fat in food with polyunsaturated fat and promoting public awareness about diet and physical activity, including through mass media. These might seem intuitive and straightforward; however, pressure from multinational companies with vested interest and difficulty in changing lifestyle habits that have been formed over many years make it a formidable challenge and one which will not be easily achieved; however, in high-income countries, focus on prevention and improved treatment following cardiovascular events has resulted in significantly reduced rates of mortality [1].