**3.1 Global cardiovascular risk estimate using traditional risk factors**

Given that risk factors for CVDs do not act in isolation, quantification of risk is an important part of the risk stratification process. The prediction of an individual's ASCVD risk over a one 10-y period traditionally involves assessment of CVD risk factors such as age, gender, baseline levels of systolic and diastolic BP, serum cholesterol, smoking status and history of diabetes. Published in 1998 [47] and modified in 2002 [48], the Framingham risk score (FRS) derived from the Framingham Heart Study (FHS) which is broadly granted as the pioneering longitudinal cohort study [49, 50]. FHS chart, a risk prediction model, assigns weight (points) to traditional risk factors for ASCVD such as age, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), treated or untreated SBP (yes or no), smoking status (yes or no), and type-2 diabetes (yes or no). This FHS chart produces an estimate (or risk) of developing CVD or a component of CVD (such as stroke, peripheral vascular disease, or heart failure) over a fixed time, for example, the next 10 years [50]. Also, Framingham investigators presented heart /vascular age which is the age that corresponds to a person with normal risk factors and the same 10-year CV risk stating that low 10-year risk can cohabit with a vascular age higher than the chronological one [51]. FHS chart has been broadly utilized for clinical guidelines [52], transported, and validated in several non-Framingham settings [53].

Besides the Framingham estimate functions, other significant risk functions such as the European Systematic Coronary Risk Evaluation (SCORE) function, the Prospective Cardiovascular Münster (PROCAM) function [53], the QRISK [54, 55] algorithms, the Reynolds risk score [56, 57], the Multi Ethnic Study of Atherosclerosis (MESA) algorithms may be used [58]. The final objective of all these ASCVD risk prediction models should be to improve clinical guidelines in detecting silent and undiagnosed CVD. Nevertheless, there are some caveats to using these risk factors alone in a model as prognostic tools for CVD risk prediction. Most of these risk equations have been constructed with data from Western populations, are generally population-specific, and may not be safely extrapolated to other populations. One must consider the fact that the calculated risk does not mean the occurrence of event in any specific individual but rather in 100 individuals with identical features.

For aviation personnel, rigorous medical scrutiny leads to the exclusion of those with evident CVDs at either initial or renewal of their medical licenses [2]. CVD events are often silent or may present without warning. All the licensed

aviation personnel undergo CV assessment including electrocardiogram (ECG), echocardiography, and lipid profile at initial. An ECG can be done at renewal as appropriate.

Several Civil Aviation Authorities (CAA) highly recommend aircrew, chiefly those aged 40 years or more, to periodically be screened for cardiovascular risk using suitable risk investigative tools that comprise family history and non-fatal and fatal end points, and a resting ECG. For most aircrew, the Reynold's risk equation provides a reasonably well-calibrated risk estimate, which includes family history [57]. The assessment and management of aeromedical risk continue to be a balancing act between practicality, risk tolerance and the advances of diagnostic medicine. The risk, which can be considered as a minimum objective for a large public transport aircraft due to medical causes, lies in the region of 10−8 and 10−9 per hour or per flight as appropriate.

A single risk matrix cannot reflect the operational impact of a medical event for all aircrew roles. To reflect the operational impact of a medical event incorporating aircrew role, a series of risk matrices that reflect the varying operational risk pertinent to specific aircrew role (the third dimension) is required. This led Gray et al. to develop a three-sized risk matrix, which embodies discrete aircrew duties: (i) aircrew with direct control over the aircraft (ie, pilot, copilot), (ii) aircrew personnel with input to navigation or engine/mechanical systems (ie, navigator, FEs), and (iii) aircrew responsible for passenger or cargo (ie, loadmasters, cabin crew) [4]. Although technically, air traffic controllers (ATCs) are not considered crews, they are considered to have an attributable risk similar to that of pilots.

Thus, ICAO asks stakeholder countries to use ASCVD estimate scores in aeromedical risk assessment to help alleviating morbidity and mortality in aeronautical setting. For example, the New Zealand Guideline Group (NZGG) adjusted [59], updated [60], and even assessed [61] the Framingham ASCVD estimate tools. In a matched case–control study accounting Oceania- based airline pilots using the NZGG adjusted Framingham score, Wirawan posited the NZGG score had low sensitivity and thus missed to predict 47% of the CV events [62].

#### **3.2 Global cardiovascular risk estimate using new and emergent risk factors**

Risk in CVD is still assessed chiefly by clinical features such as age, hypertension, diabetes mellitus, hyperlipidemia, and family history. Nonetheless, biochemical, cellular, and imaging frameworks are firmly allowing for increasingly improved risk assessment.

Aircrew undergo various investigations to assess cardiovascular risk that are anatomical (Cardiac CT, cardiac MR or invasive coronary angiography, transthoracic and transesophageal echocardiography), physiological (Myocardial perfusion imaging, including perfusion MRI, myocardial perfusion scintigraphy [MPS], both single photon emission CT [SPECT] and positron emission tomography [PET]), stress echocardiogram (with either physiological or pharmacological stress) and fractional flow reserve (FFR) and Clinical (Exercise stress ECG test, CAC scoring). Exercise stress ECG test is not recommended as a solely investigative tool for assessment of significant CAD in aircrew [63]. It is relevant to note that the negative predictive value (NPV) of the CCT for the detection of CHD is almost 100%, which implies that a negative scanner is very reassuring at least for the next 35 years [64].

To comply with the approach of the ICAO, it is recommended to CAAs to hold an inventory of the effective of aircrew to monitor their careers and health, their accidents and impairments [65]. Even for private aircrew, there are concerns, which imply that some degree of restriction must be applied. On the other hand, several CAAs prohibit pilots aged 65y or older from flying on commercial flight operations

#### *Risk Factors for Cardiovascular Diseases in Aircrew DOI: http://dx.doi.org/10.5772/intechopen.99905*

even if this remains debatable [63]. The so-called "age-65 rule" is of concerns about the potential deleterious effects of aging on pilots' safety performance [66].

Aircrew with elevated cardiovascular risk established on inceptive screening should go through intensified screening that includes ancillary, to name but a few, stress ECG, CAC scoring solely, or combined with a CT coronary angiogram (CTCA) investigation, and vascular ultrasound imaging (VUI). Second-line investigative risk tools for CAD assessment comprise functional imaging, and invasive coronary angiography (ICA). Emerging technologies comprise CMR for plaque imaging and FFR that is a technique traditionally used as an adjunct to ICA to measure pressure differences across coronary stenosis.

Exercise stress ECG provides useful risk-stratification information including aerobic fitness, BP response and arrhythmia assessment, which may be incorporated in intensified screening. The use of routine exercise stress testing as a sole screening tool for CAD is not supported by evidence and is not recommended. Exercise stress tests are limited in their ability to detect potentially flow-limiting CAD and to predict future cardiovascular events. Because of its restricted sensitivity and specificity, exercise stress ECG has a flaw as screening test for coronary atherosclerosis. Moreover, because of its very low PPV for future coronary events, stress ECG should be discouraged as a stand-alone tool to determine aeromedically significant CAD.

The Astro-CHARM tool is the first integrated ASCVD risk calculator to incorporate risk factors, including hs-CRP, family history, and CAC data. It improves risk prediction in comparison with traditional risk factor equations and could be useful in risk-based decision making for cardiovascular disease prevention in the middleaged general population.

Ultrasound imaging of the carotid and femoral arteries provides easily accessible visualization of vascular anatomy without radiation. cIMT and carotid and femoral artery plaque, have been evaluated as markers for cardiac disease and stroke risk. Several prospective studies have shown that the presence of carotid and femoral bifurcation plaques is associated with future cardiovascular events, independent of other risk factors. Guidelines support the use of carotid artery ultrasound in the cardiovascular risk assessment of asymptomatic aircrew at intermediate risk.

To identify aeromedically significant CAD, physiological imaging such as stress echo, perfusion MRI or myocardial perfusion scintigraphy (MPS) has limited utility and is not recommended as the sole secondary investigation for aircrew considered to be at high cardiovascular risk as it may overlook aeromedically significant (aggregate) stenosis. ICA should be reserved for those aircrew who are deemed at high risk for significant CAD or where accurate delineation of percentage coronary stenosis is required. ICA currently remains the gold standard for anatomical imaging of coronary arteries. This is because the spatial resolution of ICA is superior to that of CTCA. CTCA is less accurate than ICA for quantifying luminal stenosis. The threshold for initiating enhanced screening of aircrew with increased estimated risk for a coronary event is an organizational decision.
