**5. Assessment of feasibility and exclusion of contraindications for TAVI**

A severely calcified aortic valve may result in the inability to cross the native valve with the catheter. Bulky leaflets and calcifications on the free edge of the leaflets may increase the risk of occlusion of the coronary ostia during aortic valve implantation. Therefore, the extent and exact location of calcifications should be carefully assessed before the implantation pro‐ cedure. Assessing coronary anatomy is also important in the selection process. Conventional coronary angiography, which remains the "gold standard", should be done to exclude the

**Figure 4.** Invasive diagnostic prior TAVI, including aortography and access vessels as well as transvalvular gradient

**4. Analysis of surgical risk and evaluation of life expectancy and quality**

The precise evaluation of surgical risk in a specific patient is not easy and involves an at‐ tempt at individualization based on statistical data from databases containing a large num‐ ber of procedures. The most accepted and validated algorithms that are widely available today are the EuroSCORE, the STS (Society of Thoracic Score) score,and the Parsonnet score. These algorithms predict the surgical risk by assigning weight to various factors that affect the clinical result, but it is clear that they can underestimate or overestimate the risk in cer‐ tain groups of patients who are not represented satisfactorily in the population used to gen‐ erate the algorithm [8]. There is some evidence in the literature of the incorrect prediction of aortic AVR outcome using the EuroSCORE model [9]. The key element for establishing whether patients are at high risk for surgery is multidisciplinary clinical judgment, which should be used in association with a more quantitative assessment, based on the combina‐ tion of several scores (for example, expected mortality >20% with the EuroSCORE and >10% with STS score). This approach allows the team to take into account risk factors that are not covered in scores but often seen in practice, such as chest radiation, previous aortocoronary

presence of significant coronary artery disease (Figure 4).

bypass with patent grafts, porcelain aorta, liver cirrhosis.

**of life**

486 Calcific Aortic Valve Disease

After criteria of severe symptomatic aortic valve stenosis and high surgical risk are evaluat‐ ed, the technical evaluation of the patient's suitability for the percutaneous implantation technique begins (Table 1).

**Table 1.** Actually proposed indications and contraindications for TAVI

The two most basic parameters are the suitability of the peripheral arteries and the size of the aortic valve annulus. Contrast angiography is needed to assess the former, while the lat‐ ter requires an initial assessment of the diameter of the aortic annulus on a TTE. In general terms, a large artery with dominant elastic elements should have a diameter up to 1 mm smaller than the external diameter of the sheath that has to be introduced for the valve im‐ plantation. Thus, current systems with an external sheath diameter of 28 F (SAPIEN 26 mm, Edwards Lifescience LLC, Irvine, CA), 25 F (SAPIEN 23 mm, Edwards) and 22 F (CoreValve, Medtronic, Inc., Minneapolis, MN) require minimum diameters of 8, 7, and 6 mm, respec‐ tively. Apart from the minimum diameter, the existence of significant vessel tortuosity (>90°), especially when combined with wall calcifications, makes advancing the large sheath problematic, with a high risk of vascular complications that could potentially affect the final outcome. In addition, the existence of extensive circumferential calcifications limits the elas‐ tic dilation of the artery; thus, the minimum diameters referred to above are underestimat‐ ed. Patients who do not meet the criteria of suitable peripheral arterial access may still be candidates for transapical implantation. For the assessment of aortic annulus diameter, we should keep in mind that TTE underestimates its size by a mean of 1.4 mm compared with TEE [6,10], while the latter method also underestimates the size by 1.2 mm compared with intraoperative measurement [10]. Therefore, in order to avoid undesirable and often cata‐ strophic displacement of the prosthesis, there should be a margin of at least 1-2 mm between the diameter of the valve and the size of the aortic annulus estimated using TEE, so that the former may be successfully and safely anchored within the latter. Computed tomography scan aortography and angiography of the ascending aorta are the most appropriate exami‐ nations for investigating these aspects. Those examinations will also be used for the meas‐ urement of the dimensions of the ascending aorta and the aortic arch, which are essential for checking eligibility for the CoreValve (the most important being the diameter of the ascend‐ ing aorta, which should be <4.3 cm) (Figure 5).

**Figure 6.** Three-dimensional reconstruction of contrast-enhanced CT angiography to assess morphology of femoral

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http://dx.doi.org/10.5772/53437

489

On the basis of first results from clinical trials, CoreValve Revalving System and Edwards Lifescience SAPIEN obtained CE mark approval in 2007 with the specification that these valves are intended for patients with a high or prohibitive risk for surgical valve replace‐ ment or who cannot undergo AVR. The first generation balloon-expandable valve was enti‐ tled Cribier-Edwards valve (Edwards Lifesciences), whereas at present the Edwards SAPIEN valve (Edwards) is commercially available (Figure 7). The Edwards Lifesciences SAPIEN THV device is a balloon-expandable valve. It consists of bovine pericardium that is firmly mounted within a tubular, slotted, stainless steel balloon-expandable stent. Two valve sizes have been developed (23mm and 26mm). At present, available prosthesis sizes are 23 and 26 mm for aortic annulus diameters between 18–22 mm and 21–25 mm, respec‐ tively. The CoreValve Revalving device is a self-expanding frame-valve prosthesis (Figure 7). It consists of a porcine pericardial tissue valve that is mounted and sutured in a multile‐ vel self-expanding nitinol frame. It is available in 26, 29 and 31 mm sizes. The device has a broader upper segment (outflow aspect), which yields proper orientation to the blood flow. The first-generation valve used bovine pericardial tissue and was constrained within a 25 French (F) delivery catheter. The second-generation valve was built with porcine pericardial tissue within a 21 F catheter to allow access through smaller-diameter vascular beds. The third-generation of the device features a catheter with a valve delivery sheath size of 18 F

arteries (left) and centerline stretched view (right)

and a follow-on shaft of 12 F.

**6. Different transcatheter aortic valves**

**Figure 5.** ECG-gated CT-scan of a patient with severe aortic valve stenosis and porcelain aorta after radiation exposure

The anatomy of the thoracic aorta (any chance of porcelain aorta) and the abdominal aorta should be studied by some imaging method for the existence of extensive atheromatosis, mural thrombi and aneurysm (Figure 6).

**Figure 6.** Three-dimensional reconstruction of contrast-enhanced CT angiography to assess morphology of femoral arteries (left) and centerline stretched view (right)

### **6. Different transcatheter aortic valves**

terms, a large artery with dominant elastic elements should have a diameter up to 1 mm smaller than the external diameter of the sheath that has to be introduced for the valve im‐ plantation. Thus, current systems with an external sheath diameter of 28 F (SAPIEN 26 mm, Edwards Lifescience LLC, Irvine, CA), 25 F (SAPIEN 23 mm, Edwards) and 22 F (CoreValve, Medtronic, Inc., Minneapolis, MN) require minimum diameters of 8, 7, and 6 mm, respec‐ tively. Apart from the minimum diameter, the existence of significant vessel tortuosity (>90°), especially when combined with wall calcifications, makes advancing the large sheath problematic, with a high risk of vascular complications that could potentially affect the final outcome. In addition, the existence of extensive circumferential calcifications limits the elas‐ tic dilation of the artery; thus, the minimum diameters referred to above are underestimat‐ ed. Patients who do not meet the criteria of suitable peripheral arterial access may still be candidates for transapical implantation. For the assessment of aortic annulus diameter, we should keep in mind that TTE underestimates its size by a mean of 1.4 mm compared with TEE [6,10], while the latter method also underestimates the size by 1.2 mm compared with intraoperative measurement [10]. Therefore, in order to avoid undesirable and often cata‐ strophic displacement of the prosthesis, there should be a margin of at least 1-2 mm between the diameter of the valve and the size of the aortic annulus estimated using TEE, so that the former may be successfully and safely anchored within the latter. Computed tomography scan aortography and angiography of the ascending aorta are the most appropriate exami‐ nations for investigating these aspects. Those examinations will also be used for the meas‐ urement of the dimensions of the ascending aorta and the aortic arch, which are essential for checking eligibility for the CoreValve (the most important being the diameter of the ascend‐

**Figure 5.** ECG-gated CT-scan of a patient with severe aortic valve stenosis and porcelain aorta after radiation exposure

The anatomy of the thoracic aorta (any chance of porcelain aorta) and the abdominal aorta should be studied by some imaging method for the existence of extensive atheromatosis,

ing aorta, which should be <4.3 cm) (Figure 5).

488 Calcific Aortic Valve Disease

mural thrombi and aneurysm (Figure 6).

On the basis of first results from clinical trials, CoreValve Revalving System and Edwards Lifescience SAPIEN obtained CE mark approval in 2007 with the specification that these valves are intended for patients with a high or prohibitive risk for surgical valve replace‐ ment or who cannot undergo AVR. The first generation balloon-expandable valve was enti‐ tled Cribier-Edwards valve (Edwards Lifesciences), whereas at present the Edwards SAPIEN valve (Edwards) is commercially available (Figure 7). The Edwards Lifesciences SAPIEN THV device is a balloon-expandable valve. It consists of bovine pericardium that is firmly mounted within a tubular, slotted, stainless steel balloon-expandable stent. Two valve sizes have been developed (23mm and 26mm). At present, available prosthesis sizes are 23 and 26 mm for aortic annulus diameters between 18–22 mm and 21–25 mm, respec‐ tively. The CoreValve Revalving device is a self-expanding frame-valve prosthesis (Figure 7). It consists of a porcine pericardial tissue valve that is mounted and sutured in a multile‐ vel self-expanding nitinol frame. It is available in 26, 29 and 31 mm sizes. The device has a broader upper segment (outflow aspect), which yields proper orientation to the blood flow. The first-generation valve used bovine pericardial tissue and was constrained within a 25 French (F) delivery catheter. The second-generation valve was built with porcine pericardial tissue within a 21 F catheter to allow access through smaller-diameter vascular beds. The third-generation of the device features a catheter with a valve delivery sheath size of 18 F and a follow-on shaft of 12 F.

**7. Implantation approaches**

trans-axillary access [11].

(Figure 8).

**7.1. The transapical approach**

**Figure 8.** TAVI using the transapical approach

**7.2. The transfemoral approach**

With regard to the delivery systems and their introduction into ascending aorta, two specific pathways have been explored so far: the antegrade pathway, which uses direct transapical access, and the retrograde pathway, which uses either transfemoral or trans-subclavian or

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491

The main advantages of using transapical procedures are: [1] the feasibility does not rely on the absence of a concomitant peripheral vascular disease or previous aortic surgery; [2] the delivery system seems to be more "steady" and the procedure itself more "straightforward"; and [3] this access potentially reduces the risk of calcium dislodgement due to the passage of a stiff transfemoral device into a diseased aortic arch. A transapical approach can be used in the operating room, in a hybrid room, or in a catheterization laboratory with a patient un‐ der general anesthesia. Regardless of where the transapical approach is done, it is a prereq‐ uisite that high-quality fluoroscopic imaging must be guaranteed. Apical bleeding is very rare, mostly related to patient tissue fragility or to the team learning curve, and represents the most dangerous complication related to transapical access itself. In transapical TAVI, the cardiac apex is prepared through a small left anterolateral mini-thoracotomy using a pursestring or a crossing suture reinforced by pledgets and, after the procedure, a chest tube is routinely inserted into the left pleura with pain releasers injected in the intercostal tissue

The transfemoral approach is used mostly in cardiac catheterization laboratory or a hybrid room. One of the main advantages of this technique is that it allows fully percutaneous im‐ plantation in conscious patients, as long as the peripheral vessels are of an adequate caliber (more than 6mm diameter), there are no very tortuous vessels, and vascular closure devices

**Figure 7.** Profile of the CoreValve Revaving System (A) and Edwards SAPIEN Transcatheter Heart Valve (B)

Newer devices that have first-in-man application include Paniagua (Endoluminal Tech‐ nology Research, Miami, FL), Enable (ATS, Minneapolis, MN), AoTx (Hansen Medical, Mountain View, CA), Perceval (Sorin Group, Arvada, CO), Jena (JenaValve Technology, Wilmington, DE), Lotus Valve (Sadra Medical, Campbell, CA), and Direct Flow percuta‐ neous aortic valve (Direct Flow Medical, Inc., Santa Rosa, CA). TAVI represents a unique challenge for anesthesiologists. As with other invasive procedures, a careful preoperative assessment, appropriate intraoperative monitoring and imaging, meticulous management of hemodynamics, and early treatment of expected side effects and complications is of ut‐ most importance. An unexpected decrease or increase in systemic vascular resistance re‐ sulting in decreased coronary perfusion pressure or acute heart failure by elevated left ventricular end-diastolic pressure should be avoided by maintaining a normotensive blood pressure and heart rate between 60 bpm and 100 bpm. The choice of anesthetic technique, either local anesthesia with mild sedation promoting spontaneous respiration, deep intravenous sedation with insertion of a laryngeal mask, or general anesthesia, var‐ ies among centers and is probably not associated with a significant difference in out‐ come. Post valvuloplasty and implantation, which were done under rapid right ventricular pacing due to reduce left ventricular ejection and cardiac motion, may require some additional inotropic support. Tracheal extubation can usually be done at the end of the procedure. Close postoperative monitoring is necessary, and admission to an inten‐ sive care unit is required. However, at present a retrograde approach through the femo‐ ral artery is used. During the procedure, a balloon valvuloplasty is first done to facilitate passage of the native aortic valve. During rapid right ventricular pacing, the prosthesis is positioned and deployed under fluoroscopy and echocardiographic guidance. Alternative‐ ly, in patients with difficult vascular access because of extensive calcifications or tortuosi‐ ty of the femoral artery or aorta, a transapical approach can be used. After a partial thoracotomy, direct puncture of the apical portion of the left ventricular free wall is done to gain catheter access to the left ventricle and aortic valve. The prosthesis is subsequent‐ ly positioned and deployed, similar to the antegrade approach.


Bioactive Compounds from Vegetal Sources

#### **Chapter 4**

## Beneficial Effects of Extra Virgin Olive Oil Rich in Phenolic Compounds on Cardiovascular Health

*Imen Ghorbel, Mariem Chaâbane, Naziha Grati Kammoun and Najiba Zeghal*

#### **Abstract**

The Mediterranean diet (Med-diet) includes a high consumption of cereals, fruits, legumes and vegetables, a moderate fish intake and a low consumption of red meat. Olive oil is a basic component of the Med-diet due to its numerous health benefits. In the last decade, many epidemiological studies have confirmed the protective role of extra virgin olive oil (EVOO) against several chronic illnesses including cardiovascular diseases. EVOO is mainly composed of triacylglycerols, with oleic acid as the dominating esterified fatty acid, and other minor compounds. Among them, phenolic compounds, such as hydroxytyrosol and its derivatives (oleuropein and tyrosol), are the principal components responsible for the cardioprotective effects. They are endowed with wide biological activities, including strong antioxidant properties, allowing the prevention of cardiovascular risk factors, such as atherosclerosis, plasma lipid disorders, endothelial dysfunction, hypertension, obesity and type 2 diabetes. The aim of the present chapter was to elucidate the beneficial effect of EVOO, as part of the Mediterranean-style diets, on cardiovascular risk factors and to discuss the underlying mechanisms by which polyphenols exert their effects.

**Keywords:** olive oil, phenolic compounds, cardiovascular diseases, endothelial dysfunction, atherosclerosis, type 2 diabetes mellitus

#### **1. Introduction**

The Mediterranean diet (Med-diet) is beneficial for the human health as it provides for the consumer foods rich in biological active substances. It is composed of fish, unsaturated fats, whole grains, fruits and vegetables, nuts and legumes. Olive oil has been traditionally used as the main fat in the Mediterranean regions, and recently, it has become more popular worldwide. Extra virgin olive oil (EVOO) is obtained from the fruit of the olive tree by mechanical or other physical means as follows: washing, decantation or centrifugation, and filtration. A Med-diet rich in olive oil supplies an average of 10–20 mg of phenols per day [1]. The lipophilic fraction

represents 90.0–99.0% of EVOO and it is mainly composed of phospholipids and triacylglycerols, while the hydrophilic fraction (0.5–1.5%) contains hydrocarbons, aliphatic alcohols, sterols, pigments, and several volatile and phenolic compounds [2]. Phenols are the organic molecules characterized by the existence of a hydroxyl group attached directly to the benzene ring. The major classes of phenolic compounds present in olive oil are phenolic acids, phenolic alcohols, secoiridoids, and flavonoids [3]. They have the capacity to donate the hydrogen atom of the phenolic hydroxyl group to free radicals. Hydroxytyrosol (HT), one of the main phenolic compounds of EVOO, reduces oxidative stress by improving lipid profile and inhibiting inflammatory cells [4]. The wide biological activities of HT are associated with its strong antioxidant and radical-scavenging activities [5]. HT and oleuropein, another major phenolic component of EVOO, are potent scavengers of hydroxyl radicals (OH. ), peroxynitrite (ONOOH), and superoxide radicals ( ⋅− O ) 2 [5]. Phenols are able to modulate redox status through direct action on enzymes, proteins and different signaling pathways. The oxidative stress process plays a crucial role in the development of cardiovascular diseases (CVDs). It contributes to the pathogenesis of atherosclerosis, endothelial dysfunction, plasma lipid disorders and hypertension. It has been reported that EVOO has beneficial effects on cardiovascular risk factors, such as coagulation, platelet aggregation, fibrinolysis, endothelial dysfunction and lipid metabolism alteration [6]. Moreover, EVOO shows potential actions on markers of inflammation related to CVD, such as interleukin 6 and C-reactive protein [7].

The aim of the present chapter was to present some evidence from previous studies demonstrating the beneficial effect of EVOO, as part of the Mediterranean-style diets, on cardiovascular risk factors, namely atherosclerosis, plasma lipid disorders, endothelial dysfunction, hypertension, obesity and type 2 diabetes mellitus (T2D), and to discuss the underlying mechanisms by which polyphenols exert their effects.

#### **2. Phenolic compounds present in EVOO**

In olive oil, both simple and complex phenolic compounds contribute to its stability and affect its sensory properties.  According to Bajoub et al. [3], the most abundant phenolic compounds can be classified according to their chemical structure as follows: secoiridoids (oleuropein, oleuropein aglycone, oleocanthol), simple phenols (tyrosol, HT), lignans (pinoresinol, syringaresinol), flavonoids (luteolin, apigenin) and phenolic acids (**Figure 1**). It has been demonstrated that the variability of those phenols can be related to a combination of agronomic and technological processes [8]. Indeed, once ingested, olive oil polyphenols give rise to different metabolites which are able to reach tissues and exert their beneficial effects [9]. Natural phenols have been demonstrated to modulate cell redox status through direct actions on enzymes, proteins, receptors and different signaling pathways [10, 11].

#### **3. EVOO polyphenols and CVD**

In recent years, several studies have demonstrated the cardiovascular health benefits associated with the regular consumption of olive oil with a high polyphenol content. Hence, understanding the mechanisms contributing to the favorable effect

*Beneficial Effects of Extra Virgin Olive Oil Rich in Phenolic Compounds on Cardiovascular… DOI: http://dx.doi.org/10.5772/intechopen.104883*

**Figure 1.**

*The phenolic compounds present in olive oil.*

**Figure 2.**

*Cardioprotective effects of phenolic compounds present in olive oil.*

of these bioactive compounds is of crucial importance. In this setting, the main mechanisms responsible for the cardioprotective effects of olive oil polyphenols against atherosclerosis, plasma lipid disorders, endothelial dysfunction, hypertension, obesity and T2D will be reviewed (**Figure 2**).

#### **3.1 Polyphenols and atherosclerosis**

It has been known that several CVD are directly related to thrombus formation [12]. The oxidative stress process, an imbalance between reactive oxygen species

(ROS) production and endogenous antioxidant defense system, plays a crucial role in the development of heart diseases. An excessive production of ROS causes oxidative damage to the vascular endothelium [13] by promoting vascular cells proliferation, apoptosis, and necrosis which may result in the formation of atherosclerotic plaques leading to thrombosis [13, 14]. The uncontrolled ROS formation alters the vascular tone, which is mediated by a decrease of nitric oxide (NO) bioavailability, the most potent endogenous vasodilator [15]. A low NO level is associated with the promotion of platelet aggregation, adhesion of inflammatory cells and fibrinolysis which are responsible for the developmental process of atherosclerotic plaques [16]. Olive oil intake contributes to the homeostasis of the thrombogenic profile by improving the production of coagulation factors and biomarkers related to platelet aggregation [17]. Oleuropein and HT have been shown to exert several protective effects *in vivo* on a model of atherosclerosis inhibiting endothelial activation and monocyte-endothelial cell adhesion [18]. Besides, these simple phenolic compounds have been described as the potent inhibitors of platelet aggregation in several *in vitro* experiments [19].

#### **3.2 Polyphenols and plasma lipid disorders**

Plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels are included in CVD risk assessment tools. The elevated levels of TC and LDL-C have been considered as risk factors for atherosclerosis, which is the primary cause of CVD. LDL-C is the main carrier of circulating cholesterol to the target vascular cells. Consequently, circulating LDL-C is a valuable indicator of the amount of lipid accumulation in the arterial wall. Their oxidation is considered to be the triggering factor for the biochemical processes leading to atherosclerotic plaque formation in the sub-endothelial space [20]. Apolipoprotein B (Apo B) is the primary protein component of LDL-C, while apolipoprotein A (Apo A) is the primary protein component of HDL-C. Polyphenols affect apolipoproteins (Apo) A and B, modify LDL-C particles, and reduce plasma triglyceride (TG) levels by increasing the lipoprotein lipase activity, which decreases LDL-C concentrations in the blood circulation [21, 22]. The mechanism by which polyphenols reduce hepatic Apo B production relies on their binding with the plasma membrane transport P-glycoprotein, which inhibits cholesterol esterification [23]. The administration of EVOO phenols to rats co-exposed to aluminum and acrylamide leads to the improvement of their blood lipid profile by reducing TC and increasing HDL-C levels [11]. It has been reported that oxidized LDL-C concentration decreases after a high-phenolic olive oil intake [24]. Moreover, the 3-month consumption of a Med-diet supplemented with virgin olive oil reduces TC and LDL-C and increases HDL-C in high-cardiovascular-risk participants [25].

#### **3.3 Polyphenols and endothelial dysfunction**

Endothelial cells are able to synthesize molecules, such as NO and endothelin 1 (ET-1), substances with vasodilator and vasoconstrictor activities, respectively [26, 27]. An imbalance between vasodilating and vasoconstricting molecules induces endothelial dysfunction. At the cellular level, ROS can neutralize the vasodilator NO, inactivate protein tyrosine phosphatases, increase intracellular free calcium concentrations, and act as second messengers within redox-dependent signaling pathways [28]. Endothelial dysfunction, a critical event in the development of hypertension, is controlled by several vasoactive peptides such as angiotensin II and endothelin-1 [29]. *Beneficial Effects of Extra Virgin Olive Oil Rich in Phenolic Compounds on Cardiovascular… DOI: http://dx.doi.org/10.5772/intechopen.104883*

The high content of phenolic compounds present in EVOO may slow the atherogenic process by inhibiting oxidative damage and restoring endothelial function. In fact, EVOO phenols decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase endothelin-1 synthesis in ECV304 cells incubated with high glucose and fatty acid concentrations [30].

#### **3.4 Polyphenols and hypertension**

Hypertension is a serious medical condition characterized by a persistent elevation of the blood pressure in the arteries and reflects a hypersensitivity of the vascular smooth muscle to vasoconstrictor stimuli [31]. It corresponds to a systolic blood pressure (SBP) of 140 mmHg or more and/or to a diastolic blood pressure (DBP) of 90 mmHg or more [32]. It is recognized as one of the strong causes leading to cardiovascular stroke and myocardial infarction [33]. Oxidative stress has been shown to be the fundamental mechanism responsible for hypertension [34]. Other factors, such as inflammation, endothelial dysfunction and vascular remodeling, have been also documented as key contributors to this condition [33]. Reactive oxygen species are involved in the homeostasis of the vascular wall, and particularly in the modulation of the vasomotor system. Superoxide anion can even play the role of a vasoconstrictor agent and it can rapidly react with NO, decreasing the bioavailability of this vasodilator molecule [35]. Enhanced ROS generation and reduced NO levels, in addition to reduced antioxidant status, have been reported in hypertensive humans and animals [36, 37].

On the other hand, several studies have demonstrated that olive oil polyphenols have vasoprotective effects on blood pressure. Moreno-Luna et al. [38] have shown that the daily intake of a polyphenol-rich olive oil diet during 8 weeks is effective in reducing peripheral SBP and DBP in young women with mild hypertension. Recently, Sarapis et al. [39] have reported a decrease in both central and peripheral SBP in healthy adults after the daily consumption of EVOO with high polyphenols content during 3 weeks. The anti-hypertensive effects of olive oil have been mainly attributed to its phenolic compounds. In fact, administration of isolated polyphenols from olive oil, like oleuropein, has shown a positive correlation with the improvement of the hypertensive state [40]. Several mechanisms have been proposed for the blood-pressure lowering effects of olive oil polyphenols. They include, for example, suppression of the oxidative stress and inflammatory processes, enhancement of the endothelial synthesis of NO [38], and modulation of the expression of genes connected to the renin–angiotensin system [41].

#### **3.5 Polyphenols and obesity**

During the past few decades, obesity has been considered as a chronic disease resulting from multiple interactions between genetic and lifestyle factors. It is characterized by an increase in the number and size of adipocytes in adipose tissue leading to the development of T2D, CVD and hyperlipidemia [42]. Adiponectin, a major adipocyte -secreted adipokine, is abundantly present in the circulation of healthy humans exerting anti-diabetic and anti-inflammatory activities [43]. In obese individuals, its levels are decreased through mechanisms involving chronic inflammation, oxidative stress and atherosclerosis, which are factors responsible for the development of CVD [43]. Therefore, dietary strategies are effective in modulating adiponectin secretion by the improvement of inflammation-associated adipocyte dysfunction to reduce the risk of obesity-related CVD. Previous studies have suggested that olive polyphenols can inhibit pre-adipocyte differentiation, suppress lipogenesis, induce lipolysis, and regulate adiponectin secretion [44, 45]. HT, at nutritionally relevant concentrations, induces adiponectin down- regulation in human adipocytes through the attenuation of adipogenesis- related genes (JNK-mediated PPARγ) expression [43]. Additionally, Drira et al. [45] have reported that HT and oleuropein at concentrations of 100 and 150 μM and 200 and 300 μM respectively, reduce pre-adipocyte differentiation and lipid accumulation and thus regulate the size of fat cells on 3T3 –L1 cells. It has been proposed that oleuropein may diffuse through the lipid bilayer of the cell membrane and may be absorbed via a glucose transporter [46]. These data indicate that EVOO phenols may play a protective role against excessive fat accumulation by inhibiting the differentiation rate of adipocytes and down-regulation of the adipogenesis-related genes. Therefore, olive oil polyphenols have great effects on the adipogenesis process and can be helpful in the prevention and treatment of obesity-related metabolic and CVDs in humans.

#### **3.6 Polyphenols and diabetes**

Diabetes is a chronic metabolic disease which can affect over time the entire body, and particularly the cardiovascular system. Compared to non-diabetic subjects, people suffering from diabetes, notably type 2 diabetes (T2D), have an increased chance of developing CVD [47]. Furthermore, cardiovascular complications represent the main cause of mortality among diabetic patients [48]. These complications can be manifested at the vascular and the cardiac levels. The key pathologic diabetic pathways affecting the vasculature include oxidative stress, alteration of vascular progenitor cells, microvascular dysfunction and impairment in reverse cholesterol transport [49]. Diabetes can also predispose the myocardium to specific structural and functional damages, a condition known as diabetic cardiomyopathy (DCM) in diabetic patients. Several molecular events are known to trigger DCM such as alterations in the metabolism of glucose, ketones, fatty acids and amino acids, impairment of insulin signalling, calcium mishandling, oxidative stress and inflammation [50].

Growing evidence from human and animal researches supports the positive outcome of olive oil consumption, especially EVOO, on diabetes management. Results from the "Prevención con Dieta Mediterránea" (PREDIMED) study have shown a lower incidence of T2D mellitus with an increasing adherence to a Med-diet rich in EVOO in patients at high CVD risk [51]. Also, a Med-diet supplemented with virgin olive oil has been observed to improve glucose metabolism and insulin sensitivity in subjects with T2D [52]. Besides, the daily intake of a polyphenol-rich EVOO during 8 weeks has been demonstrated to significantly reduce the levels of fasting plasma glucose and circulating inflammatory adipokines (cytokines involved in glucose metabolism) in overweight patients with T2D [53]. In an animal study performed on T2D mice, EVOO administration for 24 weeks has been reported to lower fasting glycemia, insulinemia and insulin resistance and to ameliorate β-cells' function [54]. It has been suggested that polyphenols present in EVOO may contribute significantly to its protective role against diabetes [53, 55]. Among them, HT and oleuropein have been demonstrated to display anti-diabetic actions in both *in vivo* and *in vitro* studies [56–58]. Polyphenols might influence glucose metabolism through reducing the digestion and the intestinal absorption of dietary carbohydrates, stimulating insulin secretion, and improving glucose uptake in the tissues by modulating intracellular signaling [59]. Due to their antioxidant properties, these bioactive compounds could

*Beneficial Effects of Extra Virgin Olive Oil Rich in Phenolic Compounds on Cardiovascular… DOI: http://dx.doi.org/10.5772/intechopen.104883*

also inhibit the formation of advanced glycation endproducts, which results in the protection of pancreatic β-cells against glucotoxicity [60].

#### **4. Conclusions and future perspectives**

In summary, multiple beneficial effects on CVD risk factors have been associated with the consumption of Med-diet patterns rich in EVOO. The cardioprotective effects of polyphenols present in olive oil are mediated through the inhibition of atherosclerosis, hypertension, obesity and diabetes, amelioration of the plasma lipid profile and improvement of the endothelial function. The consumption of a Med-diet supplemented with olive oil is therefore recommended, as it could serve as a functional food beyond basic nutrition. Further efforts are needed to elucidate the pharmacokinetics and pharmacodynamics underlying the potential effect of EVOO phenolic compounds and the dose-dependence of their effects in humans.

#### **Author details**

Imen Ghorbel1 \*, Mariem Chaâbane1 , Naziha Grati Kammoun2 and Najiba Zeghal1

1 Sciences Faculty of Sfax, Animal Physiology Laboratory, University of Sfax, Sfax, Tunisia

2 Laboratory of Resources of the Olive Tree: Characterization, Valorization and Phytosanitary Protection, Technology and Quality Research Unit, Olive Tree Institute, University of Sfax, Sfax, Tunisia

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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### Section 3


**1. Background**

The concepts of quality of work life (QWL) and job satisfaction are interrelated, when attempting to define a good work environment or a good and healthy life. Sirgy et al. [1] state that QWL relates to job satisfaction in the sense that job satisfaction is one of many outcomes of QWL. Job satisfaction is crucial because it influences job performance, customer satisfaction, employment retention, employee absenteeism, and organizational commitment [2].  In fact, women working from home during the COVID-19 lockdown experienced a set of negative effects from working remotely, namely the invasion of privacy, family time, the occurrence of distractions while working resulting in failures, and the increasing interference of work in private life [3]. Therefore, the focus of QWL goes beyond job satisfaction. It involves the effect of the workplace on satisfaction with the job; satisfaction in non-work life domains; and satisfaction with overall life, personal happiness, and subjective well-being [1].

Work occupies one's thoughts, determining decisions and thus contributing to one's social identity [4]. Such subjective and behavioral components of the QWL, namely supervisors' support, a good work environment, and collaborative support from co-workers, as well as the feeling of being respected professionally and personally, have an important influence on forming an employee's individual desire to contribute to the organization's productivity. This is also supported by the statement that QWL is associated with job

**Citation:** Pereira, D.; Leitão, J.; Ramos, L. Burnout and Quality of Work Life among Municipal Workers: Do Motivating and Economic Factors Play a Mediating Role? *Int. J. Environ. Res. Public Health* **2022**, *19*, 13035. https://doi.org/10.3390/ ijerph192013035

Academic Editor: Paul B. Tchounwou

Received: 30 August 2022 Accepted: 9 October 2022 Published: 11 October 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

139

satisfaction, motivation, productivity, health, job security, safety, and well-being, embracing four main axes: a safe work environment, occupational healthcare, appropriate working time, and an appropriate salary [5,6].

With the increasing workloads of the past decades, plus the COVID-19 pandemic, the number of employees experiencing psychological problems related to occupational stress has increased rapidly, raising costs in terms of absenteeism and loss of productivity and also increasing healthcare consumption and raising public health issues in the long term [7]. Conversely, not only at the employees' level, but also at the level of SME owners, who faced, during the COVID-19 crisis, high stress, mostly derived from the shortage of personnel, financial constraints, liquidities, repeated closures, and reopenings, as well as great difficulty in adapting to such a changing environment [8].

Added to the above, occupational stress and self-reported sleep quality are also strongly associated with both QWL and work ability, highlighting the urgent need for the screening and handling of these health issues [9]. Occupational stress leads to organizational burnout, whose effects were formerly analyzed as moderators of the relationship between employees' QWL and their perceptions of their contribution to the organization's productivity by integrating the QWL factors into the trichotomy of (de)motivators of productivity in the workplace [10]. Our previous findings suggest that QWL hygiene factors (e.g., safe work environment and occupational healthcare) have an important influence on productivity, and burnout de-motivator factors (that is, low effectiveness, cynicism, and emotional exhaustion) significantly moderate the relationship between QWL and the contribution to productivity.

The COVID-19 pandemic—which has been (and will continue to be) a key issue throughout and beyond the 2020s—had an effect on individual–organizational relations and consequently, on organizational performance [11]. This took a toll not only on frontline workers (physicians, nurses, and hospital workers) but also on other public servants, such as municipal workers, not studied so far, who were affected by the changing the location of their work, tasks, the demands at work, and the demands they face outside work, endangering the balance between professional and personal life [12,13].

Furthermore, the financial insecurity and financial stress that already interfered with work [14] increased unexpectedly as COVID-19 aggravated these concerns. Due to the COVID-19 pandemic, employees are generally more aware of financial security. According to Kulikowski and Sedlak (2020), studies on work engagement and job performance have shown that employees ranked financial security as a factor of the highest significance [15]. These concerns could trigger stress, impacting employees' health and leading to mental illnesses such as post-traumatic stress disorder (PTSD) [13] but also high rates of tension, anger, anxiety, depressed mood, mental fatigue, and sleep disturbances. Such problems, usually referred to overall as distress, are often classified as neurasthenia, adjustment disorders, or burnout [7,16]. Focusing on younger, unmarried female healthcare workers with low monthly incomes who were studied in Jordan during the pandemic, they revealed high anxiety symptoms, which were exacerbated one year after the beginning of COVID-19, particularly for the physicians, with intense schedules, and those who were infected [17]. This situation is intensified in the public healthcare system, during pandemics, as it is characterized by a scarcity of resources and reduced accountability, thus increasing the lack of trustworthiness in the health system [18]. Strategies to improve healthcare systems' efficiency, physicians' motivation, management routines, patient flows, and information are a need during extreme crises, such as COVID-19. These strategies were implemented in a nodal-designated COVID-19 center in Qatar and proved to be effective, lowering mortality and increasing efficacy, capabilities, and patient satisfaction [19].

Furthermore, employees' mental health has a positive relationship with job performance, although this same relationship is mediated by innovative behavior and work engagement, which are also positively associated with job performance [20].

Knowledge on the influencers of QWL has remained relatively limited. In order to forecast and make possible an anticipated action on the part of responsible managers, it is essential to assess hypothetical unexplored effects associated with other mediating factors of the core relationship between burnout and QWL [21].

Set against this background, a relevant research question arises concerning the need to advance the still limited knowledge about other types of motivating and economic mediators affecting municipal workers' QWL, especially in terms of disorders associated with burnout, in the context of the COVID-19 pandemic. An effective response to the COVID-19 pandemic required effective administration, which in turn depended on the effort and capacity of millions of public sector workers from the front line to central administration. Added to the above, for many public servants, COVID-19 has fundamentally changed not only where and how they work but also the increasing demands of their jobs and day-to-day life [12].

#### **2. Burnout during COVID-19 for Public Servants**

When the World Health Organization (WHO) declared the outbreak of a new coronavirus disease (COVID-19) and then characterized it as a pandemic, all working people were affected. Not only because of their (or their relatives') health, but also due to the implications for the workplace. Here, we can identify three main groups of people who could be affected by burnout, namely: (a) people who kept their jobs and continued to work in the same location, (b) people who kept their jobs but started to work from home, and (c) people who lost their jobs.

The term "burnout" was first used by Freudenberger (1974), who described his own experience as "a combination of feelings, exhaustion and fatigue, a lingering cold, headache and gastrointestinal disturbances, sleeplessness and shortness of breath" [22]. The discussion on burnout has grown since then, being continuously updated in terms of symptoms but also in terms of consequences, not only for the employee, but also for the employer.

The multidimensional theory of burnout [23–25] defines burnout as being grounded in three core components: (i) emotional exhaustion, as the individual stress dimension of burnout, refers to energy depletion or the draining of emotional resources; (ii) depersonalization, which represents the interpersonal dimension, refers to the development of negative, cynical attitudes towards the recipients of one's service or care; and (iii) reduced or lack of personal accomplishment, which refers to a decline in one's feeling of competence and successful achievement in one's career; this is the self-evaluation dimension of burnout. Furthermore, burnout is characterized by: (a) loss of enthusiasm for work; (b) psychological exhaustion; (c) indolence, and the appearance of negative attitudes and behaviors towards patients and the organization; and (d) the appearance, in some cases, of feelings of guilt [26].

Globally, burnout entails a state of physical, emotional, and mental exhaustion resulting from a long period of involvement in highly emotional demanding work situations [27]. Burnout is a psychological syndrome of exhaustion, cynicism, and inefficacy in the workplace. It is also considered to be an individual stress experience embedded in a context of complex social relationships, involving a person's perception of both the self and others on the job [28,29], associated with limited resources, low abilities, and low energies and interest in long-term work [30]. This condition involves emotional exhaustion, depersonalization, and a lack of personal accomplishment. Burnout can arise through stress disorders triggered by stress on the job and is also often defined as an emotional-exhaustion experience by employees [15,31]. Theoretical frameworks such as the JD-R model claim that high, unfavorable job demands are consistently related to burnout [32–36]. Moreover, the combination of those high demands with low job resources can lead to some kind of long-lasting burnout and employee disengagement.

As a phenomenon that is context-specific, it is worthwhile to try to deepen the stillscarce knowledge about the impact of pandemic circumstances on occupational health, insofar as it has influenced working conditions, involvement, QWL, and burnout levels, bearing in mind the limited knowledge about the situation for public servants, including municipal workers. According to Meyer et al. (2021, p. 1) [37], " ( ... ) the COVID-19 pandemic poses new challenges for employees' psychological health that go beyond previous findings in the area of demands and resources (e.g., [35,38]).

The spread of COVID-19, followed by swift responses by companies and governments, created many new challenges that have brought about profound changes and affected the normal health routines and lifestyles of people of all ages, restricting outdoor or physical activity, increasing sedentary time, and consequently, disrupting sleep [39]. Nevertheless, the same authors outline that the isolation of workers at home had mixed effects on adult health behaviors in China, stressing that those workers focused more on their eating quality and patterns, which had a positive influence on their quality of life. The biggest change for most workers was the remote work experience. Prior to COVID-19, most workers had little remote working experience, nor were they or their organizations prepared to adopt this practice. Now, the unprecedented pandemic has required millions of people across the world to become remote workers, inadvertently leading to a de facto global experiment on remote working [40,41]. According to a study by Moretti et al. (2001) of the home-working population, home workers perceived themselves to be less productive compared to their office working period and less satisfied due to isolation [42].

In this respect, COVID-19 highlights employees' and employers' vulnerability. As many businesses around the world will be restructured or disappear due to the pandemic, workers will be retrained or laid off and the economic, social–psychological, and health costs of these actions are likely to be immense. Indeed, the impacts of the pandemic affect some groups of workers more than others, for example, based on their age, race and ethnicity, gender, or personality [41]. These impacts were affirmed by Wang et al. (2021), who stated that, as schools in China shut down during the COVID-19 outbreak, working parents faced a challenge in balancing work and family roles and time, creating higher levels of exhaustion, depression, and burnout [40].

Blake at al. (2020) conducted a survey of frontline/healthcare workers to understand the psychological impacts on employees and how these translated into negative consequences for organizations [43]. They found that the extreme pressure experienced by workers during the COVID-19 pandemic might increase their risk of burnout, which has adverse outcomes, not only for their individual well-being, but also for patient care and for the healthcare system. In addition, fear of exposure to COVID-19 or even due to the scarcity of personal protective equipment (PPE), allocation of resources, accountability, and the efficient management of patient flows, as well as a lack of or a reduction in training on practical skills to deal with emergency situations and critical care, can put even more pressure on frontline/health professionals [18,44]. There is also the fear of taking the disease home or even being responsible for bringing it to the workplace, infecting other patients. All this combined with the normal challenges of supporting a family, changes in workload and schedules, and facing new or unknown clinical situations may substantially increase levels of anxiety, emotional strain, and physical exhaustion.

At the coalface of the pandemic, healthcare workers and public service providers have jobs and occupations that have proven to be associated with increased mental health problems during pandemic crises and high personal and work-related burnout [13].

A survey applied to Portuguese healthcare workers during the COVID-19 pandemic, wherein frontline working positions were associated with higher levels of stress and depression, showed a significant association with increased burnout levels. In this survey, higher levels of satisfaction with life and resilience were highly associated with lower levels of burnout [45]. This is also supported in the research developed by Hofmam and Hubie (2020), wherein surveys conducted among frontline workers from two health units in Cascavel-PR (Brazil) identified that all participants obtained higher than expected burnout scores, emotional exhaustion, and a feeling of low professional achievement [46].

Pandemics bring new ways of performing jobs in several sectors of activity, including among public servants not directly working in health-related areas, as happens with municipal workers. The institutionalization of remote working and the rapid, sometimes reckless, digitalization by companies and public organizations has increased the frequency of workers' burnout with consequences for families' personal life and budget [47].

During the COVID-19 pandemic, municipal workers working in sectors closer to citizens were forced to work remotely, which has caused unique supervisory demands for human resources managers [12], as well as exacerbated burnout caused by self-isolation policies, which can increase social isolation and relationship difficulties [48].

Other public sector activities and their workers, for instance, those connected with education, were also put under pressure by the effects of pandemics. Marelli et al. (2021) showed a high percentage of both students and university administration staff workers denoting symptoms of depression or anxiety [49], and Evanoff et al. (2020) pointed out the important prevalence of stress, anxiety, depression, work exhaustion, burnout, and worsened well-being among university employees [50]. Another study on insomnia among employees in occupations critical to the functioning of society (e.g., health, education, welfare, and emergency services) during the COVID-19 pandemic also found that employees reported higher levels of insomnia symptoms compared to normative data collected before the pandemic [51]. These findings only highlight the associations of health and well-being with additional personal and work factors beyond the COVID-19 pandemic, without addressing the role played by motivating and economic mediators of the relationship between burnout and QWL.

A study of social workers in the United States during the COVID-19 pandemic, showed a high level of PTSD and burnout symptoms among the participants enrolled in frontline jobs dealing directly with the risk of contagion [52]. Bapuji et al. (2020) stated that organizational and societal inequalities feed into each other, giving rise to concerns that growing inequality after COVID-19 will also contribute to a downward spiral of negative trends in the workplace in the form of decreased work centrality and increased burnout, absenteeism, deviant behaviors, bullying, and higher job rotation [53].


*Edited by Arli Aditya Parikesit*

The approaches in drug design are mainly comprised of these three multidisciplinary sciences. First, Bioinformatics has successfully gather biological data in form of biomolecular sequences, in order to construct knowledge on drug and vaccine design. It is of considerable importance for drug designers to comprehend the utilization of bioinformatics tools for resolving their research questions. Second, Nanotechnology has made possible the design and delivery of the nano-based drug. Third, Pharmaceutical Chemistry made it possible to investigate the adsorption, distribution, metabolism, and toxicology of the drug candidates in a fine-grained resolution.

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**9. Conclusion and way forward**

The paper has demonstrated that in the context of Botswana, standard of living and well-being have varied by historical period, beginning from pre-colonial, through colonial, and post-colonial eras to the present. Also evident is the fact that community development has been a key tool for promoting social development, with a view to improving standard of living and wellbeing of the population. The variations in levels of social provision noted, have essentially been a function of the social and economic changes, and challenges that the country has experienced over the years, and which in some respects it continues to experience. However, despite the noted challenges, Botswana's socioeconomic trajectory, including its social protection regime, remains quite robust and has, over the years, grown from strength to strength. Be that as it may, a number of shortfalls have been noted in regard to the social development efforts of the country, particularly if Sen's capabilities framework is used to define standard of living and well-being.

Some commentators have expressed concern that the government's approach to some community development initiatives has tended to be rather top-down, suggesting lack of participation of the masses in decision making. This of course does not augur well for successful community development. Ferguson-Brown [73], among others, argued that the top-down approach (to community development) which involves trying to change attitudes to suit national plans rather than identifying needs at community level may actually have alienated the people. Alienated people do not participate; they may become overly dependent on the government. The government does seem to admit that some of its strategies may have inadvertently created a dependency syndrome among the populace. The Ministry of Local Government, for instance, while addressing this theme, observed that emphasis on service delivery, rather than on strengthening community governance structures for economic empowerment, had led to unbridled dependency on government social support mechanisms [55].

The country's social protection regime appears to be doing relatively well. According to the Regional Hunger and Vulnerability Programme (RHVP),

#### *Standard of Living, Well-Being and Community Development: The Case of Botswana DOI: http://dx.doi.org/10.5772/intechopen.97680*

Botswana boasts of one of the most comprehensive state-led social protection regimes in the southern African region. The same agency further noted that in Botswana, "Programming for poor, vulnerable and excluded groups is comprehensive by African standards…." ([62]: 1). The RSVP has gone so far as to claim that the social protection system in Botswana can serve as a 'model for Africa'. Even so, concerns have been raised in respect of the social protection system, and these include the apparent tendency on the part of the relevant authorities to simply focus on ensuring that social protection services are made 'available' and 'accessible' to everyone who qualifies, without putting sufficient attention to whether indeed the services are actually 'being utilized' by all concerned. Apparently, this has essentially been a function of inadequate monitoring and evaluation measures in place [28]. Other areas of concern raised in regard to social protection initiatives in place include lack of clear mechanisms that are in place for effective redistribution of the national wealth. Such is bound to impact negatively on standards of living and wellbeing.

RHVP [62]: 3 has observed thus, "*While most Batswana have benefited from these achievements, the new wealth is very unevenly distributed and many individuals and groups are marginalized economically, socially and/or geographically*". Other than that, there has been concern that the social protection schemes had tended to suffer from lack of coordination, poor implementation, ineffective utilization of resources and lack of accountability [28]. Concern has also been expressed to the effect that some of the schemes have promoted a dependency syndrome. Gadbolae [74], for instance, argued that one of the social protection schemes (Destitute Persons Programme) had ushered in a dependency syndrome. What was needed, he argued, are effective mechanisms to facilitate capacity building and empowerment with a view to facilitate self-reliance.

To its credit though, the government appears to be open to learn from experience, which in itself is a major plus. It (government) has continued to push ahead with its community development agenda, as well as expansion of its social protection regime meant to benefit mainly the needy. It is little wonder therefore that Statistics Botswana [75] reported a decline in the overall number of persons living below the poverty datum line from 499,467 in 2002/3 to 373, 388 in 2009/10. Though more recent figures were not immediately available, this positive trend appears to be continuing, suggesting the standard of living and wellbeing of the population (as defined by Sen,) continues on an upward trajectory, credit to the various community development initiatives currently in place across the country.