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.

In this blog you will learn:
- How does smoking affect the arteries?
- How does diabetes mellitus affect the arteries?
- How does hypertension affect the arteries?
- How does hyperlipidaemia affect the arteries?
- How do different risk factors, including family history, synergistically affect the arteries?
How does smoking affect the arteries?
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 [9]. 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.
How does diabetes mellitus affect the arteries?
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 [25]. 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 [25]. This may explain the association of diabetes with atherosclerosis in the distal arteries [25]. 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].
How does hypertension affect the arteries?
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) [30]. However, although aggressive but appropriate management of hypertension is warranted in virtually all cases, the same could not be said for hyperlipidaemia.
How does hyperlipidaemia affect the arteries?
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 [40]. Other associated risk factors may also obstruct the proper management of LDL-C.
How do different risk factors, including family history, synergistically affect the arteries?
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.
[1] Role of Smoking in Global and Regional Cardiovascular Mortality > https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.104.521708
[2] Global estimate of the burden of disease from second-hand smoke > https://apps.who.int/iris/bitstream/handle/10665/44426/9789241564076_eng.pdf
[3] The health consequences of smoking. Cardiovascular diseases > https://www.ncbi.nlm.nih.gov/pubmed/1548965
[4] Cardiovascular risks associated with smoking: a review for clinicians > https://www.ncbi.nlm.nih.gov/pubmed/16874138
[5] Smoking promotes pathogenesis of aortic aneurysm through the 5-lipoxygenase pathway > https://www.ncbi.nlm.nih.gov/pubmed/15823697
[6] Very low nicotine content cigarettes and potential consequences on cardiovascular disease > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525710/
[7] Smoking and Aortic Diseases > https://www.jstage.jst.go.jp/article/circj/71/8/71_8_1173/_article
[8] The effect of smoking on arterial stiffness > https://www.nature.com/articles/hr201025
[9] Cigarette smoking and cardiovascular disease: pathophysiology and implications for treatment > https://www.sciencedirect.com/science/article/abs/pii/S0033062003000872
[10] Meta-analysis of the association between cigarette smoking and peripheral arterial disease > https://heart.bmj.com/content/100/5/414
[11] The Influence of Smoking Cessation on Hemodynamics and Arterial Compliance > https://journals.sagepub.com/doi/abs/10.1177/0003319706293119
[12] Relationship of smoking and smoking cessation with ankle-to-arm blood pressure index in elderly Japanese men > https://www.ncbi.nlm.nih.gov/pubmed/16575279
[13] Influence of smoking on incidence and prevalence of peripheral arterial disease > https://www.ncbi.nlm.nih.gov/pubmed/15622370
[14] Medical management of claudication > https://www.jvascsurg.org/article/S0741-5214(17)30915-1/fulltext
[15] Smoking Cessation in Peripheral Artery Disease > https://www.acc.org/latest-in-cardiology/articles/2020/03/05/07/53/smoking-cessation-in-peripheral-artery-disease
[16] Cardiovascular complications in diabetes mellitus > https://www.ncbi.nlm.nih.gov/pubmed/15780822
[17] Peripheral Arterial Disease in Patients With Diabetes > https://www.sciencedirect.com/science/article/pii/S0735109705028627
[18] Management of coronary artery disease in patients with type 2 diabetes mellitus > https://link.springer.com/article/10.1007/BF02938374
[19] Diabetes, the Metabolic Syndrome, and Ischemic Stroke > https://care.diabetesjournals.org/content/30/12/3131
[20] Racial differences in the incidence of femoral bypass and abdominal aortic aneurysmectomy in Massachusetts: Relationship to cardiovascular risk factors > https://core.ac.uk/download/pdf/81134207.pdf
[21] Prevalence and Associations of Abdominal Aortic Aneurysm Detected through Screening > https://annals.org/aim/article-abstract/710383/prevalence-associations-abdominal-aortic-aneurysm-detected-through-screening
[22] The Aneurysm Detection and Management Study Screening Program > https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485324
[23] Reduced Aortic Wall Stress in Diabetes Mellitus > https://www.ejves.com/article/S1078-5884(06)00660-5/fulltext
[24] Matrix biology of abdominal aortic aneurysms in diabetes: mechanisms underlying the negative association > https://www.ncbi.nlm.nih.gov/pubmed/17522995
[25] Regional Differences in the Expression of Nitric Oxide Synthase and Specific Receptors in the Vascular Tissues of Control and Diabetic Rabbits: A Pilot Study > http://iv.iiarjournals.org/content/21/6/1069.full.pdf
[26] The changing epidemiology of diabetic microangiopathy in type 1 diabetes > https://link.springer.com/article/10.1007/s00125-005-1836-x
[27] Diabetic nephropathy and retinopathy > https://www.sciencedirect.com/science/article/abs/pii/S0025712504000628
[28] Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting > https://academic.oup.com/brain/article/130/8/1988/307128
[29] Secondary prevention of ischemic stroke: evolution from a stepwise to a risk stratification approach to care > https://www.ncbi.nlm.nih.gov/pubmed/17961080
[30] Traditional Risk Factors Are Predictive on Segmental Localization of Coronary Artery Disease > https://journals.sagepub.com/doi/abs/10.1177/0003319708318379
[31] Intensity of lipid-lowering therapy and low-density lipoprotein cholesterol goal attainment among the elderly before and after the 2004 National Cholesterol Education Program Adult Treatment Panel III update > https://www.sciencedirect.com/science/article/abs/pii/S0002870307003614
[32] Reducing the risk of coronary heart disease via lipid reduction > https://www.ncbi.nlm.nih.gov/pubmed/15467018
[33] Peripheral arterial disease: a missed opportunity to administer statins so as to reduce cardiac morbidity and mortality > https://www.ncbi.nlm.nih.gov/pubmed/15720252
[34] Statins and Peripheral Arterial Disease: Potential Mechanisms and Clinical Benefits > https://www.annalsofvascularsurgery.com/article/S0890-5096(07)60192-7/fulltext
[35] The Effect of Short-Term Treatment with Simvastatin on Renal Function in Patients with Peripheral Arterial Disease > https://journals.sagepub.com/doi/10.1177/000331970405500108
[36] The Effect of Short-term Lipid Lowering with Atorvastatin on Carotid Artery Intima Media Thickness in Patients with Peripheral Vascular Disease: A Pilot Study > https://www.tandfonline.com/doi/abs/10.1185/0300799009117026
[37] Characteristics and Treatments of Patients with Peripheral Arterial Disease Referred to UK Vascular Clinics: Results of a Prospective Registry > https://www.ejves.com/article/S1078-5884(06)00659-9/fulltext
[38] Pharmacologic risk factor treatment of peripheral arterial disease is lacking and requires vascular surgeon participation > https://europepmc.org/article/med/17349357
[39] Knowledge and attitude of physicians in a major teaching hospital towards atherosclerotic risk reduction therapy in patients with peripheral arterial disease > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2350143/
[40] Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study > https://n.neurology.org/content/70/24_Part_2/2364
[41] Effect of cigarette smoking on lipid profile in the young > https://www.ncbi.nlm.nih.gov/pubmed/11256905
[42] Effect of smoking on lipid profile and lipid peroxidation in normal subjects > https://www.ncbi.nlm.nih.gov/pubmed/17193899
[43] C-reactive protein (CRP): more than just an innocent bystander? > https://www.ncbi.nlm.nih.gov/pubmed/18021498
[44] Smoking and Aortic Diseases > https://pdfs.semanticscholar.org/c964/9225eb8bd99f1452519632ff8d8b0b7380bd.pdf
[45] Fibrinogen: a predictor of vascular disease > https://www.ncbi.nlm.nih.gov/pubmed/17584095
[46] Genetics of type 1 diabetes mellitus > http://europepmc.org/article/med/17551474
[47] Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A > https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703779/
[48] Genetics of Type 2 diabetes > https://www.ncbi.nlm.nih.gov/pubmed/15842505
[49] Genetic basis of type 2 diabetes mellitus: implications for therapy > https://www.ncbi.nlm.nih.gov/pubmed/16026108