Metabolic syndrome (MS) is not a single disease but a cluster of metabolic disorders such as abdominal obesity, atherogenic dyslipidemia, elevated blood pressure (BP), insulin resistance (IR), and higher glucose levels [1]. For decades, there has been a debate on the proper definition and diagnostic criteria of MS. There are different versions of the criteria for diagnosing MS, often taking into account different parameters, which may hinder the comparability of the research results obtained by different authors and make it difficult to conduct scientific discourse ^{[2][3][4][5][6][7][8][9][10]}[2,3,4,5,6,7,8,9,10]. The International Diabetes Federation (IDF) issued a consensus in accordance with the American Heart Association (AHA) and the National Heart, Lung and Blood Institute (NHLBI) in 2009. According to the mentioned consensus, MS can be diagnosed if at least three of the five conditions in Table 1 are met [11].

Central obesity	increased waist circumference (cut-off values for male and female gender differ between populations and countries)
Impaired carbohydrate metabolism	fasting venous blood glucose concentration ≥ 100 mg/dL or pharmacological treatment of diagnosed carbohydrate metabolism disorders
Impaired lipid metabolism	triglycerides blood level ≥ 150 mg/dL (1.7 mmol/L) or pharmacological treatment of this lipid disorder
	high-density lipoprotein cholesterol blood level < 40 mg/dL in men or < 50 mg/dL in women, or pharmacotherapy for this lipid disorder
Arterial hypertension	systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg, or taking of antihypertensive drugs by a patient with diagnosed arterial hypertension

MS is linked to an increased risk of developing type 2 diabetes mellitus (T2DM) and its complications. Cardiovascular diseases (CVDs) are one of the most important causes of morbidity and mortality in the population of patients living with T2DM ^[12][13][14][12,13,14]. Moreover, T2DM increases the risk of restenosis, which diminishes the efficacy of endovascular treatment of atherosclerotic CVD, worsens prognosis and may lead to the necessity of reintervention [15]. MS was shown to be associated with increased oxidative stress. Obesity and IR are the MS component that contributes the most to this relationship [16]. On the other hand, the role of oxidative stress in the pathogenesis of CVD is well established [17]. Although achieving a target low-density lipoprotein cholesterol (LDL-C) concentration adequate to the patient’s cardiovascular risk is one of the most important therapeutic goals in patients with atherosclerotic CVD [18], it should be noted that lipoproteins may be modified, especially by pro-oxidative factors that make them dysfunctional and more atherogenic, which means that the total concentration of individual plasma lipid fractions does not provide full knowledge about the state of the patient’s lipid metabolism [19].

1.2. Assessment of Arterial Stiffness

According to the American Heart Association as well as European experts’ consensus, the measurement of pulse wave velocity (PWV) remains a standard method to assess AS ^[20][21][22,23]. There are different devices applicable to the measurement of PWV, based on such methods as tonometry, oscillometry, ultrasonography, and magnetic resonance imaging ^[22][24]. However, there are some limitations to the measurement of PWV. Specialized equipment and experienced personnel are required to perform the measurement. In addition, care should be taken to ensure that the measurement is carried out in appropriate conditions, such as, among others: a quiet, dry room, ensuring thermal comfort; moreover, the measurement should be carried out after a ten-minute rest in a lying position. The BP value and heart rate (HR) should also be taken into account during the interpretation of the PWV value, as these parameters can influence the PWV measurement result ^[20][22].

2. Impact of Metabolic Syndrome Components on Arterial Stiffness

2.1. Elevated Blood Pressure

Increased systolic blood pressure (SBP) or diastolic blood pressure (DBP) are both MS components. In patients with high cardiovascular risk such as patients with MS, it is crucial to assess subclinical dysfunction of the cardiovascular system in order to initiate preventive measures, adequate life changes, and treatment early ^[23][24][25,26]. There are studies, both in humans and animals, that suggest that AS can precede high BP ^{[25][26][27][28]}[27,28,29,30]. Increasing AS defines the loss of the arterial wall’s resistance to expansion by an increment in volume; as a result, it is linked to increased BP ^[29][30][31,32]. AS is closely related to aging, as the aorta and major arteries lose elasticity. As compensation, they undergo dilatation, which results in widened pulse pressure ^[31][32][33,34]. The effectiveness of this compensative mechanism is, however, limited by the greater arterial stiffening during systole in the large stiffer artery. The gold standard for measuring AS remains the velocity of arterial pressure waves, despite their limitation and dependence on age, BP, and HR ^[33][34][35][35,36,37]. Moreover, elevated serum leptin levels may influence the potential mechanism leading to sympathetic activation and therefore increasing PWV and elevated BP ^[36][38].

2.2. Central Obesity

When considering abdominal obesity, it has been shown that in obese patients the PWV is significantly higher compared to normal healthy individuals, proving that abdominal obesity is a significant factor in the development of AS ^[37][38][39][48,49,50]. BMI, visceral fat thickness, and fat mass are the strongest body fat measures related to PWV ^[40][41][42][51,52,53].  In a prospective study performed by Kae-Woei Liang, it has been proved that after a three-month weight reduction program, brachial–ankle PWV in patients with obesity and MS, compared to the healthy control group, decreased slightly. However, in those in whom weight regaining was observed in a sixty-month follow-up period, compared to the healthy control group that also experienced weight regaining, the brachial–ankle PWV increased by a significantly higher amount. Interestingly, brachial–ankle PWV at the 60th month after weight regaining in obese patients with MS was even worse than the baseline values, was associated only with SBP or DBP increments, and when compared to healthy individuals proves to be beyond the aging process. In addition, brachial–ankle PWV values after weight regaining were independent of body weight, high-sensitivity C-reactive protein (hs-CRP), or insulin resistance changes ^[43][56]. However, it is still unknown what impacts a decrease in PWV value after weight reduction the most; whether it depends on changes in adipokines and inflammatory markers or is due to weight reduction per se ^[44][45][57,58].

2.3. Lipid Metabolism Disorders

Dyslipidemia is a metabolic disturbance associated with an impaired concentration of basic lipid parameters, such as blood level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and/or the presence of dysfunctional lipoproteins in the blood [19]. The whole spectrum of possible underlying pathophysiological mechanisms of the influence of lipid profile on atherosclerosis has not yet been well established. Lipid disorder may lead to cardiovascular disease in different ways ^[46][64]. Elevated TG level has been shown to promote endothelial dysfunction by stimulating the expression of endothelial mediators, such as endothelin-1 ^[47][48][65,66]. An elevated triglyceride glucose index (TyG) was associated with a significantly increased risk of AS and nephric microvascular damage ^[49][50][67,68]. However, the relationship between elevated TG and AS is not completely clear ^[51][69].

2.4. Impaired Carbohydrate Metabolism

AS increases in patients with MS and IR ^[52][53][78,79]. Prediabetes metabolic variables affect AS and accelerated arterial aging from an early age ^[54][55][80,81]. The clinical diagnosis of IR is useful for assessing the risk of T2DM ^[56][82]. When assessing the IR index there is a need for insulin level measurement, which is a limitation of such indexes due to their high cost and variability depending on the utilized technique ^[57][83]. Recently described non-insulin-based IR index, the metabolic score for insulin resistance (METS-IR), was developed with the aim to quantify peripheral insulin sensitivity. METS-IR is a function of such variables as glucose level, BMI as well as TG and HDL-C levels ^[58][84].

3. Metabolic Syndrome and Pulse Wave Velocity

MS is a group of cardiometabolic disorders. AS may explain the increased risk of CVD in patients with MS ^[59][86]. In a study by Kangas et al., it has been documented that PWV was 16–17% higher in patients with MS compared to the healthy control group.  Some efforts have been made to find the determinants of AS in patients with MS beyond PWV. A body shape index (ABSI) calculated from waist circumference, BMI, and body height has been confirmed to identify people with MS and increased AS ^[60][93]. Nedogoda et al. have documented carotid–femoral PWV to be a better parameter for early vascular aging estimation in patients with MS in comparison to clinical scales, Systematic COronary Risk Evaluation (SCORE) scale, QRESEARCH cardiovascular risk algorithm (QRISK-3) scale, and Framingham scale ^[61][94]. Patients diagnosed with arterial hypertension have a high prevalence of metabolic syndrome regardless of controlled or resistant hypertension ^[62][95]. Hypertensive patients with MS were shown to be older (57.9 ± 12.2 vs. 52.7 ± 14.1 years, p < 0.001) and to have higher PWV (9.0 ± 2.3 vs. 8.4 ± 2.1 m/s, p = 0.001) than those without MS ^[63][96]. Predicting the risk of cardiovascular events in MS patients is crucial. In a prospective study involving 2728 middle-aged patients with MS, the occurrence of at least one cardiovascular event was associated with higher mean BP, aortic PWV, aortic augmentation index, and carotid intima-media thickness (p < 0.05 for all variables) ^[64][97]. 

4. Importance of Analyzed Research in Routine Clinical Practice

MS, as a group of metabolic disorders, is strongly associated with subclinical vascular damage, marked by increased PWV value ^[65][66][99,100]. As proved in the cited literature as well as a study performed by Gagliardino, PWV is significantly impaired in patients with complete pictures of MS. Furthermore, the level of PWV is significantly increasing with the increasing number of MS components, supporting the need for careful research for the early diagnosis of CVD in patients with MS as a cost-effective preventive strategy ^[67][68][101,102]. Moreover, higher glucose levels in the prediabetic range and IR might lead to higher AS and concentric remodeling of the heart muscle ^[69][103].

Abdominal obesity is an important component of MS. The ambulatory AS index of the obese subjects is significantly higher than in the healthy controls ^[70][71][72][104,105,106]. Moreover, sensitivity analyses demonstrated that higher PWV is associated with waist circumference-to-BMI ratio and it remains significant after adjustment for HR, metabolic risk factors, and inflammatory markers ^[73][74][107,108]. It is crucial for obese patients who have lost weight to maintain their status, as weight regaining worsens AS with a significant increase in PWV, especially in patients with obesity and MS ^[43][56]. Moreover, it is important to pay particular attention to patients with MS and AS in whom the adverse effect of metabolic disturbances on arterial function can be offset by an adequate program of exercises, which includes mainly aerobic physical training ^[75][76][109,110]. It is important to measure PWV under stabilized BP and HR values, particularly in patients with newly diagnosed hypertension in whom detection of organ damage mediated by asymptomatic hypertension has an impact on risk stratification ^[77][78][111,112]. PWV is positively correlated with both SBP and DBP ^[79][113]. An increase in PWV is associated with a significantly higher risk of hypertension incidence ^[80][114]. However, treatment of MS components is guided by its component level and clinical vascular damage. There are no guidelines for the treatment of subclinical vascular damage based on and guided by PWV. Chronic renin-angiotensin blockade (olmesartan) has been documented to lower AS partly independently of the corresponding reduction in BP ^[81][115]. The strategy to prevent cardiovascular and renal events based on AS (SPARTE Study) has been shown to reduce office and ambulatory SBP and DBP, and prevent vascular aging, but not to reduce cardiovascular outcomes despite the higher intensity of treatment when there was PWV normalization-driven strategy treatment compared to BP-driven strategy ^[82][116]. However, as the scholarstudy authors underline, it was the first study to focus on the impact of AS on cardiovascular outcomes. Furthermore, the main limitation of the study was the small number of patients and its limited capacity for clinical events. The risk of increased AS depends on hyperlipidemia at young ages ^[83][117]. Dyslipidemia therapy guidelines are focused mainly on LDL-C lowering when considering cardiovascular outcomes. However, as shown in studies cited before, the TG/HDL-C index was shown to be positively correlated with PWV and could be considered an independent risk factor for the development of AS. Thus, even after reaching the recommended levels of LDL-C, there are still lipid disorders that may increase residual cardiovascular risk ^[84][118]. AIP demonstrates the relationship between atherogenic and preventive lipoproteins. The link between PWV and AIP supports the view that the calculation of AIP should be included in the everyday clinical evaluation of the risk of cardiovascular disease, especially due to the easy calculation of AIP from routine lipid profiles. It could be an effective predictive value to detect early vascular aging and subclinical atherosclerosis ^[85][86][119,120].

5. Conclusions

MS and its components are a significant problem for healthcare systems worldwide. CVD is the leading cause of morbidity and mortality, and, on the other hand, MS predisposes the development of CVD. The identification of patients with features of subclinical dysfunction of the cardiovascular system in the population of patients with MS and its components is also very important in clinical practice, and PWV measurement is a valuable tool for this purpose. AS defined by PWV is positively correlated with both SBP and DBP. It may indicate subclinical organ damage in patients with hypertension. In addition, the decrease in PWV level during hypertensive therapy can identify a group of patients with better outcomes independently from BP reduction. Obese patients with MS who have lost and regained weight are predisposed to have a significant increase in PWV, above their baseline levels. The adverse effect of metabolic disturbances on arterial function can be offset by an adequate program of exercises, which includes mainly aerobic physical training. The TG/HDL-C ratio demonstrates the ratio between the atherogenic and preventive lipoproteins. The increased TG/HDL-C levels ratio is positively correlated with increased PWV levels and is an independent risk factor for cardiometabolic disease, with a consecutive correlation that was not proved separately for TG and HDL-C levels. IR affects AS and accelerates arterial aging. Non-insulin-based IR index, such as METS-IR, can predict arterial stiffens due to a strong positive correlation with PWV.