There are many (cardio)vascular risk factors, but few as prominent as tobacco smoking and diabetes mellitus. However, their mechanisms are significantly different, and they do not affect all arterial beds in an equal manner. Further compounding their harmful effects are other factors like hypertension and hyperlipidaemia, which often coexist with the primary condition. Their malignant impact on cardiovascular health on their own is, however, well researched and worthwhile reading for both specialists and general practitioners.
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Tobacco smoking is the single most important modifiable risk factor for all vascular diseases, and it is estimated that it is responsible for 10% of all cardiovascular deaths globally per year (about 1.7 million), in addition to an estimated 360 thousand cardiovascular deaths due to second-hand smoking [1, 2]. It impairs flow-mediated, endothelium-dependent arterial vasodilatation, in addition to nicotine itself altering the structural and functional components of vascular smooth muscle and endothelial cells [3-8].
It also works synergistically, for lack of a better word, with other vascular risk factors like diabetes mellitus, hyperlipidaemia, and hypertension, to increase vascular morbidity and mortality . Additionally, smoking is particularly strongly associated with a higher risk of peripheral arterial disease (PAD) and abdominal aortic aneurysms (AAAs), but only weakly or the least with cerebrovascular diseases [9, 10]. Fortunately, smoking cessation reverses or at least lessens some of the harmful effects (e.g. arterial stiffness), including decreasing the overall risk of PAD, improves claudication symptoms, decreases the risk of amputation, graft failure, restenosis after endovascular revascularisation, MI and ultimately death [11-15]. Other risk factors, however, like diabetes, cannot be “turned off” and are problematic even when properly managed.
Diabetes mellitus is a well-recognised risk factor for coronary artery disease (CAD), PAD and cerebrovascular diseases, but its presence is, surprisingly, negatively associated with the development of AAAs [16-22]. The reason for this is reduced aortic wall, the underlying mechanism being increased by synthesis and reduced degradation of the matrix through the deposition of advanced glycation end products that make the matrix more resistant to proteolysis [23-24].
Studies have also shed light on the possible reasons for the variable severity of atherosclerosis in specific arterial beds . Researchers found regional differences in the distribution of endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1) and 5-hydroxytryptamine (5HT, serotonin) receptors between the aorta and renal and femoral arteries . This may explain the association of diabetes with atherosclerosis in the distal arteries . Its harmful effects on renal function (diabetic nephropathy) and vision (diabetic retinopathy) are, on the other hand, no mystery, and a cause of great concern to both patients and clinicians [26, 27].
Like smoking and diabetes mellitus, hypertension is a recognised risk factor, especially for vascular diseases like CAD and stroke. Studies have shown that hypertension is a good predictor of brain microbleeds, which are associated with first-time and recurrent ischaemic and haemorrhagic strokes [28, 29]. Additionally, hypertension was demonstrated to be associated with distal rather than proximal coronary artery atherosclerosis (CAD) . However, although aggressive but appropriate management of hypertension is warranted in virtually all cases, the same could not be said for hyperlipidaemia.
High levels of blood lipids are associated with greater incidence and morbidity for CAD and PAD, although their management at optimal levels is important for all vascular patients [31, 32]. Good management of hyperlipidaemia is particularly beneficial in PAD patients, reducing vascular events, cardiac morbidity and mortality and improving the thickness of carotid artery intima-media [33-36]. However, in practice, many of those patients are undertreated, i.e. poor management of lipid levels and general cardiovascular risk factors [37-39].
On the other hand, there is some evidence that too aggressive management may be harmful in some respects, especially in patients with stroke or transient ischaemic attack (TIAs). The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study demonstrated an increased risk of haemorrhagic stroke in patients with a recent stroke or TIA following LDL-C lowering therapy with a daily 80 mg dose of atorvastatin . Other associated risk factors may also obstruct the proper management of LDL-C.
As previously mentioned, tobacco smoking directly affects other risk factors: in the case of hyperlipidaemia, it is associated with high serum cholesterol, LDL-C and triglyceride levels and low high-density lipoprotein cholesterol concentrations [41, 42]. Likewise, there is tentative evidence of harmful effects on emerging risk factors like C-reactive protein and fibrinogen [43-45].
When talking about risk factors, we must also mention the role of family history in the development of vascular diseases. For example, diabetes mellitus type 1 and type 2 are partly inherited metabolic disorders, so given their association with a number of (vascular) diseases, it may be fair to imply that some individuals are inherently more predisposed to the development of some of them [46-49].
Risk factors, some of them inherited, for vascular diseases promote atherogenesis to a varying extent in specific arteries and often act synergistically, additionally hindering proper treatment and management.