ia_gov_sa · guide · processed · 92 chunks
المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Saudi Guidelines for Dyslipidemia Management
2022\1443
المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
The Task Force for Dyslipidemia Management Guideline
Jamilah AlRahimi \( ^{1,2,*} \) , Shukri AlSaif \( ^{3} \) , Mirvat Alasnag \( ^{4} \) , Zuhier Awan \( ^{5} \) , Fawaz Almutairi \( ^{6} \) , Hajer Al Mudaïeem \( ^{7} \) , Baris Gencer \( ^{8,9} \) , Alberico L. Catapano \( ^{10} \) , François Mach \( ^{8} \) , Adel Tash \( ^{11,12} \)
\( ^{1} \) Cardiology Department, King Faisal Cardiac Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Jeddah, Saudi Arabia
\( ^{2} \) Cardiology Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
\( ^{3} \) Saud AlBabtain Cardiac Center, Dammam, Saudi Arabia
\( ^{4} \) Catheterization Laboratory, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia
\( ^{5} \) Medicine, Biochemistry and Molecular Genetics, Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
\( ^{6} \) Security Forces Hospital, Riyadh, Saudi Arabia
\( ^{7} \) Therapeutic Affairs Deputyship, Ministry of Health, Riyadh, Saudi Arabia
\( ^{8} \) Cardiology Department, Geneva University Hospital, Geneva, Switzerland
\( ^{9} \) Institute of Primary Healthcare (BIHAM), Bern University, Bern, Switzerland
\( ^{10} \) Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy
\( ^{11} \) Cardiac Services Development, Ministry of Health, Riyadh, Saudi Arabia
\( ^{12} \) National Heart Center, Saudi Health Council, Riyadh, Saudi Arabia
Corresponding Author*: Jamilah S. AlRahimi, Assistant Professor Medicine/Cardiology, Department of Cardiac Science, King AbdulAziz Medical City- Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, College of Medicine, King Saud bin AbdulAziz University for Health Sciences, Jeddah, Saudi Arabia. Address. P.O. Box 9515, 21423 Jeddah, Saudi Arabia. Tel. 00966505616454. Fax: 920008668 ext 25809. Email. alrahimija@gmail.com.
Keywords: Guidelines • dyslipidemias • cholesterol • triglycerides • low-density lipoproteins • high-density lipoproteins • apolipoprotein B • lipoprotein(a) • total cardiovascular risk • lifestyle modifications • adherence •
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
familial hypercholesterolemia • coronary artery calcium score • pharmacological • cardiovascular disease • metabolic syndrome • diabetes mellitus • drug therapy • hydroxymethyl-glutaryl CoA reductase inhibitors/statins • hypercholesterolemia • lipids • patient compliance • primary prevention • risk assessment • risk reduction • secondary prevention • ezetimibe • proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9) inhibitors • inclisiran • health technology assessment • Saudi Arabia
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
Table of Content
Abbreviations and acronyms 7
1. Preamble 9
2. Introduction 12
3. Cardiovascular disease risk and risk groups 15
3.1. Total cardiovascular risk estimation 15
3.2. Risk categories 17
3.3. Treatment goals across total cardiovascular disease risk categories 19
3.4. Risk factors 21
3.5. Risk enhancers 30
3.6. Risk modifiers 34
3.7. COVID-19 and cardiovascular disease 37
4. Management of dyslipidemia in different clinical settings 38
4.1. Acute coronary syndromes 38
4.2. Diabetes mellitus 39
4.3. Chronic kidney disease 40
4.4. Women 40
4.5. Familial hypercholesterolemia 43
5. Regimen Selection 45
5.1. Pharmacological interventions 45
5.1.1. Recommended Pharmacological Interventions and approved indications ...... 45
5.1.2. Regimen Selection for different clinical settings 45
5.2. Monitoring of lipids and enzymes for patients on lipid-lowering therapy 55
6. Health technology assessment trends on dyslipidemia treatments 59
6.1. Healthcare system and access to care in Saudi Arabia 59
6.2. Economic burden of cardiovascular diseases in Saudi Arabia and HTA overview... 59
7. Gaps in care and strategies to encourage adoption of preventive measures 63
8. Key messages 67
9. Evidence-based ‘to do’ and ‘not to do’ 69
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
List of Tables
Table 1. Classes of recommendations and levels of evidence .... 11
Table 2. Recommendations for cardiovascular disease risk estimation in Saudi Arabia .... 17
Table 3. Cardiovascular risk categories in Saudi population .... 18
Table 4. Recommendations for lipid analyses in Saudi Arabia .... 26
Table 5. Recommendations for treatment goals for LDL-C in Saudi Arabia .... 27
Table 6. Goals for cardiovascular disease prevention in Saudi Arabia .... 28
Table 7. ASCVD risk-enhancing factors, cut-off values/conditions, and recommendations in Saudi Arabia .... 31
Table 8. ASCVD risk modifiers, cut-off values/conditions, and recommendations in Saudi Arabia .... 35
Table 9. Recommendations for dyslipidemia management in different clinical settings in Saudi Arabia .... 41
Table 10. Recommendations for FH management in Saudi Arabia .... 44
Table 11. Pharmacological interventions and approved indications .... 47
Table 12. New therapies that are being developed .... 54
Table 13. Monitoring strategies for different lipid-lowering therapies .... 55
Table 14. Recommendations for monitoring safety in patients with ASCVD during the pharmacological intervention .... 57
Table 15. Recommendations for proper HTA implementation regarding dyslipidemia treatments in Saudi Arabia 62
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
List of Figures
Figure 1. Top 10 causes of DALYs in Saudi Arabia for the periods 1990–2010 and 2010–2017, both sexes .... 14
Figure 2. Treatment goals across total cardiovascular disease risk categories .... 20
Figure 3. Prevalence of cardiovascular risk factors in Saudi Arabia .... 25
Figure 4. Prevalence of obesity in Saudi Arabia stratified by age group .... 25
Figure 5. Monitoring statins safety .... 58
Figure 6. Comprehensive solutions to encourage adoption of preventive measures in Saudi Arabia 65
Figure 7. Clinical pathway (patient journey) of ASCVD patient in Saudi Arabia .... 66
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
Abbreviations and Acronyms
<table><tr><td>ACS</td><td>Acute coronary syndrome</td></tr><tr><td>Apo</td><td>Apolipoprotein</td></tr><tr><td>ASCVD</td><td>Atherosclerotic cardiovascular disease</td></tr><tr><td>BMI</td><td>Body mass index</td></tr><tr><td>BP</td><td>Blood pressure</td></tr><tr><td>CABG</td><td>Coronary artery bypass graft surgery</td></tr><tr><td>CAC</td><td>Coronary artery calcium</td></tr><tr><td>CAD</td><td>Coronary artery disease</td></tr><tr><td>CHD</td><td>Coronary heart disease</td></tr><tr><td>CI</td><td>Confidence interval</td></tr><tr><td>CK</td><td>Creatine kinase</td></tr><tr><td>CKD</td><td>Chronic kidney disease</td></tr><tr><td>COVID-19</td><td>Coronavirus disease 2019</td></tr><tr><td>CT</td><td>Computed tomography</td></tr><tr><td>CV</td><td>Cardiovascular</td></tr><tr><td>CVD</td><td>Cardiovascular disease</td></tr><tr><td>CYP450</td><td>Cytochrome P450</td></tr><tr><td>DALYs</td><td>Disability-adjusted life-years</td></tr><tr><td>DM</td><td>Diabetes mellitus</td></tr><tr><td>eGFR</td><td>Estimated glomerular filtration rate</td></tr><tr><td>EAS</td><td>European Atherosclerosis Society</td></tr><tr><td>ESC</td><td>European Society of Cardiology</td></tr><tr><td>FH</td><td>Familial hypercholesterolemia</td></tr><tr><td>FOURIER</td><td>Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk</td></tr><tr><td>HbA1c</td><td>Glycated hemoglobin</td></tr><tr><td>HDL-C</td><td>High-density lipoprotein cholesterol</td></tr><tr><td>HIV</td><td>Human immunodeficiency virus</td></tr><tr><td>HMG-CoA</td><td>Hydroxymethylglutaryl-coenzyme A</td></tr><tr><td>HTA</td><td>Health Technology assessment</td></tr><tr><td>LDL-C</td><td>Low-density lipoprotein cholesterol</td></tr><tr><td>Lp(a)</td><td>Lipoprotein(a)</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
<table><tr><td>MACE</td><td>Major adverse cardiovascular events</td></tr><tr><td>MET</td><td>Metabolic equivalent</td></tr><tr><td>MI</td><td>Myocardial infarction</td></tr><tr><td>MOH</td><td>Ministry of Health</td></tr><tr><td>mRNA</td><td>Messenger RNA</td></tr><tr><td>ODYSSEY Outcomes</td><td>Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab</td></tr><tr><td>PCI</td><td>Percutaneous coronary intervention</td></tr><tr><td>PCSK9</td><td>Proprotein convertase subtilisin/kexin type 9</td></tr><tr><td>PHC</td><td>Primary healthcare</td></tr><tr><td>PURE</td><td>Prospective Urban Rural Epidemiology</td></tr><tr><td>RA</td><td>Rheumatoid arthritis</td></tr><tr><td>REDUCE-IT</td><td>Reduction of Cardiovascular Events with EPA-Intervention Trial</td></tr><tr><td>RR</td><td>Relative risk</td></tr><tr><td>SCORE</td><td>Systematic Coronary Risk Estimation</td></tr><tr><td>SFDA</td><td>Saudi Food and Drug Authority</td></tr><tr><td>SHC</td><td>Saudi Health Council</td></tr><tr><td>siRNA</td><td>Small interfering RNA</td></tr><tr><td>TC</td><td>Total cholesterol</td></tr><tr><td>T1DM</td><td>Type 1 diabetes mellitus</td></tr><tr><td>T2DM</td><td>Type 2 diabetes mellitus</td></tr><tr><td>TGs</td><td>Triglycerides</td></tr><tr><td>TIA</td><td>TIA Transient ischemic attack</td></tr><tr><td>WHO</td><td>World Health Organization</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
1. Preamble
Since its establishment in 2014, the Saudi Health Council (SHC) has stepped up to embrace a core mission of “establishing regulations that ensure coordination and integration among health stakeholders to improve health care in Saudi Arabia, and to be an inspirational reference to a world-class Saudi health system”. In light of this mission, SHC took over the responsibility to put forward efficient health care strategies, regulations, and policies in the Kingdom to ensure that hospitals run by the Ministry of Health (MOH) and other government agencies are operated in adherence to the principles of economic management as well as performance and quality standards.
In light of the alarming status of atherosclerotic cardiovascular disease (ASCVD) risk factors in Saudi Arabia and recent data about serious gaps in quality of healthcare delivery, specifically in areas of clinical effectiveness, patient-centered care, and patient safety [1,2], SHC has taken the worrying status of dyslipidemia in Saudi patients very seriously and assigned a task force to develop national guidelines for dyslipidemia management to be a cornerstone for the development of subsequent guidelines addressing other ASCVD risk factors amongst the Saudi population. This task force recruited Saudi experts and specialists from different regions of the Kingdom, including the Director-General of the National Heart Center and other members representing various health sectors, to typify professionals involved with managing patients with dyslipidemia. One member representing the Drug Policy and Regulation at the Saudi MOH ensured all recommendations are in line with the health economic considerations that consider both clinical- and cost-effectiveness perspectives. In addition to European experts who extensively reviewed the guidelines as well as the endorsement process. Members of the assigned Task force have volunteered their time and effort to produce these recommendations with the highest level of proficiency. The designated steering committee reviewed the previously published guidelines and related
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
statements deemed pertinent to these guidelines; thus, obviating the need to implement existing guideline recommendations of different regions. The overall aim of the present document is therefore to provide a nationwide, evidence-based policy and guidelines to implement a unified approach for the management of dyslipidemia in Saudi Arabia.
The level of evidence and the strength of the recommendation are adapted from the 2019 ESC/EAS Guidelines for the management of dyslipidemia [3], where management options were graded as per predefined scales (Table 1). A third party, RAY-Contract Research Organization (RAY-CRO), coordinated the preparation of these new guidelines and provided professional writing and editorial support. After appropriate revisions, the final document was approved by all Task Force members. All experts involved in the development of these guidelines declared no real or potential sources of conflicts of interest. These Saudi clinical practice guidelines provide recommendations applicable to Saudi patients with or at risk of developing cardiovascular disease (CVD). The guidelines summarize and evaluate available evidence with a focus on the Saudi published literature and the best-available up-to-date research evidence from other international research and guidelines. It is worth emphasizing that the European Society of Cardiology guideline recommendations, categorizations, targets, and cut-offs were the main guide while developing these Saudi dyslipidemia guidelines since it is strongly believed that the tighter control imposed by the European Society of Cardiology is the most appropriate to be implemented in Saudi Arabia.
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
Table 1. Classes of recommendations and levels of evidence
<table><tr><td></td><td>Classes of recommendations</td></tr><tr><td>Class I</td><td>Evidence and/or general agreement that a given strategy is beneficial (wording to use “recommended”).</td></tr><tr><td>Class II</td><td>Class IIa: Conflicting evidence, but in favor of usefulness (wording; “should”).Class IIb: Conflicting evidence, but usefulness is less well-established (wording; “may”).</td></tr><tr><td>Class III</td><td>Evidence or general agreement that the given strategy is not useful and may be harmful.</td></tr></table>
Adapted from [3]
Levels of evidence
<table><tr><td>Level A</td><td>Data derived from multiple randomized clinical trials or meta-analyses.</td></tr><tr><td>Level B</td><td>Data derived from a single randomized clinical trial or large non-randomized studies.</td></tr><tr><td>Level C</td><td>Consensus of opinion of the experts and/or small studies, retrospective studies, registries.</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
2. Introduction
The current recommendations state that adherence to lifestyle modifications and the use of lipid-lowering medications are the cornerstones for reducing the risk for ASCVD in patients with dyslipidemia. Nonetheless, the management of dyslipidemia undergone a number of significant changes over recent years, leading to revisions in both European and US guidelines \( [3,4] \) . Such revisions include new thresholds and goals, changes in primary and secondary preventive approaches, the new classification of the risk-enhancing factors, and new definitions for risk groups; these changes are also influenced by new equation values, recommendations, and actions \( [3–5] \) . However, the published international guideline cannot be directly applied to the Saudi population who differs in a number of aspects from European and American populations \( [6] \) .
In Saudi Arabia, the mean age of the population is younger, with 72.5% aged between 15-64 years. The Saudi population is multi-ethnic, and disparities between groups are prevalent due also to geographical and cultural factors. The annual growth rate of the Saudi population is 2.3%, with a median life expectancy of 75 years. There is a high prevalence of obesity (24.7%), and approximately 25.2% of the total population have diabetes mellitus (DM). In addition, there is a lack of primary health care units (0.6 PHC per 10,000 population) [7–10]. In Saudi Arabia, over the past years, ischemic heart disease has persisted in ranking first as the top cause of death from 2000 to 2019, followed by stroke [11]. Furthermore, cardiovascular diseases collectively remained as the leading cause of disability-adjusted life-years (DALYs*) in Saudi Arabia from 1990 until 2017 (Figure 1) [12]. Prevalence of ASCVD risk factors has been consistently high over the past decades, and multiple surveys have shown the continued high prevalence of dyslipidemia, unhealthy diet, hypertension,
*disability-adjusted life-years quantifies the health loss due to specific diseases and injuries [150]
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المركز الوطني للقلب
National Heart Center
المجلات الصحي السعودي
Saudi Health Council
[Non-Text]
smoking, obesity, physical inactivity, and diabetes in Saudi Arabia across different age groups [7,8,13–16].
In this document, the Saudi experts have provided recommendations and guidance for detailed risk assessment, the position of newer cholesterol-lowering drugs within the management algorithm, and the need for special attention to patient subgroups. Besides, the experts recommended treatment algorithms using an evidence-based approach. The guideline updated the patient risk assessment and treatment options in primary and secondary prevention using the most up-to-date evidence to inform the clinicians during the process of shared decision-making, aiming to align these decisions with the recent recommendations of the international guidelines. This document has been developed for healthcare professionals to facilitate informed communication with individuals about their cardiovascular risk and the benefits of adopting and sustaining a healthy lifestyle, and of early modification of their lipid-related cardiovascular risk. This guideline has the potential to promote up-to-date management strategies and to translate them into locally delivered healthcare services, in line with the recommendations of the World Health Organization (WHO) [6].
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Leading causes
1990
Leading causes
2010 (% change*)
Leading causes
2017 (% change**)
Figure 1. Top 10 causes of DALYs in Saudi Arabia for the periods 1990–2010 and 2010–2017, both sexes
Adapted from [12]
*Percentage change in the number of age-standardized DALYs, 1990–2007.
**Percentage change in the number of age-standardized DALYs, 2010–2017.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
3. Cardiovascular Disease risk and risk groups
3.1. Total cardiovascular risk estimation
Cardiovascular (CV) risk is the likelihood of a person to develop an atherosclerotic CV event over a defined period of time, and the total risk of developing CVD, i.e., total CV risk estimation, is determined by the combined effect of multiple risk factors which commonly coexist and act multiplicatively [3]. Risk assessment systems are used to improve management decisions by way of providing a 10-year estimate of an individual's risk for ASCVD events, and therefore, many systems have been developed and comprehensively reviewed [17–26]. Ideally, risk charts should be based on country-specific cohort data since estimating risk based on cohorts that differ greatly from the target population could jeopardize the benefit of risk charts in practical terms. However, these are not available for most countries, including Saudi Arabia [27,28].
A recent Expert Opinion was published in 2018 by Alshamiri et al. [28], in which an expert panel had convened to review the commonly used international guidelines in Asia and the Middle East and to determine their applicability in the region. There was agreement that existing risk calculators may not be suitable for Asia and the Middle East, with many concerns about the validity of these calculators in local populations. However, despite disparities on which risk calculator to use across the countries represented, the panel advocated the value of using such tools to assess CV risk. In fact, the Systematic Coronary Risk Estimation (SCORE) system [29,30] is the most adopted in Saudi Arabia despite not being yet validated for the Saudi population. It provides a relatively straightforward method and allows for recalibration for use in different populations. However, it estimates the risk of fatal CVD events only and overlooks the total CVD events which occur at a higher frequency (approximately 3- to 4-fold greater) [28,31,32]. Thus, the development of a new risk calculator that is optimized for the Saudi population, and that includes important risk
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
factors in terms of relevance to the Saudi community (including non-traditional risk factors), is a gap that needs to be met to ensure all patients are adequately assessed and managed. Recommendations for cardiovascular disease risk estimation in Saudi Arabia are presented in Table 2.
In this context, it should be recalled that the mean age of presentation with the acute coronary syndrome (ACS) in Saudi Arabia is almost 10 years younger than the average age in developed countries, and this is due to the high prevalence of poorly controlled ASCVD risk factors [33,34]. Thus, risk factor screening in Saudi Arabia, including the lipid profile, should be considered earlier than recommended in developed countries (Table 2).
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Table 2. Recommendations for cardiovascular disease risk estimation in Saudi Arabia
<table><tr><td>Recommendations</td><td>\( COR^a \)</td><td>\( LOE^b \)</td></tr><tr><td>Total risk estimation using the SCORE system is recommended in Saudi Arabia despite not being yet validated for the Saudi population.</td><td>I</td><td>C[28–30]</td></tr><tr><td>The development of a new risk calculator that is optimized for the Saudi population is recommended.</td><td>I</td><td>C [28]</td></tr><tr><td>Routine assessment using the SCORE system of asymptomatic Saudi adults >40 years of age without evidence of CVD, DM, CKD, FH, or LDL-C >4.9 mmol/L (>190 mg/dL) is recommended to calculate the 10-year risk of ASCVD.</td><td>I</td><td>C [3]</td></tr><tr><td>For Saudi adults 20 to 39 years of age, traditional ASCVD risk factors should be assessed at least every 4 years.</td><td>IIa</td><td>B[24,35,36]</td></tr></table>
ASCVD= atherosclerotic cardiovascular disease; CKD = chronic kidney disease; CVD = cardiovascular disease; DM = diabetes mellitus; FH = familial hypercholesterolaemia; LDL-C = low-density lipoprotein cholesterol; SCORE = Systematic Coronary Risk Estimation.
\( ^{a} \) Class of recommendation
\( ^{b} \) Level of evidence
3.2. Risk categories
The cut-off points used to define different risk categories in the 2019 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias [3] are recommended to be adopted in Saudi Arabia and are presented in Table 3. From a practical point, individuals with certain conditions (such as; patients with documented CVD, older individuals with long-standing DM, chronic kidney disease (CKD), familial hypercholesterolemia (FH), extreme Lipoprotein(a) (Lp(a)) elevation, coronary artery calcium (CAC) score >100, or carotid or femoral plaques) are at high or very high risk of CVD.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Table 3. Cardiovascular risk categories in the Saudi population
<table><tr><td>Very-high-risk</td><td>High-risk</td><td>Moderate-risk</td><td>Low-risk</td></tr><tr><td>Saudi individuals with any of the following:Documented ASCVD, either clinical or unequivocald on imaging.DM with target organ damagee or at least three major risk factors, or early onset of T1DM of long duration (>20 years).Severe CKD (eGFR <30 mL/min/1.73 m2).A calculated SCORE ≥10% for 10-year risk of fatal CVD.FH with ASCVD or with another major risk factor.</td><td>Saudi individuals with any of the following:Markedly elevated single risk factors, in particular total cholesterol (TC) >8 mmol/L (>310 mg/dL), LDL-C >4.9 mmol/L (>190 mg/dL), or BP ≥180/110 mmHg.Patients with FH without other major risk factors.Patients with DM without target organ damagee with DM duration ≥10 years or another additional risk factor.Moderate CKD (eGFR 3059 mL/min/1.73 m2).A calculated SCORE ≥5% and <10% for 10-year risk of fatal CVD.</td><td>Saudi individuals with any of the following:Young patients (T1DM <35 years; T2DM <50 years) with DM duration <10 years, without other risk factors.Calculated SCORE ≥1% and <5% for 10-year risk of fatal CVD.</td><td>Saudi individuals with calculated SCORE <1% for 10-year risk of fatal CVD.</td></tr></table>
Adapted from [3]
ASCVD = atherosclerotic cardiovascular disease; ACS = acute coronary syndrome; BP = blood pressure; CABG = coronary artery bypass graft surgery; CKD = chronic kidney disease; CT = computed tomography; CVD = cardiovascular disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; FH = familial hypercholesterolaemia; LDL-C = low-density lipoprotein cholesterol; MI = myocardial infarction; PCI = percutaneous coronary intervention; SCORE = Systematic Coronary Risk Estimation; T1DM = type 1 DM; T2DM = type 2 DM; TC = total cholesterol; TIA = transient ischemic attack.
\( ^{a} \) Class of recommendation
\( ^{b} \) Level of evidence
\( ^{c} \) Documented ASCVD includes previous ACS (MI or unstable angina), stable angina, coronary revascularization (PCI, CABG, and other arterial revascularization procedures), stroke and TIA, and peripheral arterial disease.
\( ^{d} \) Unequivocally documented ASCVD on imaging includes those findings that are known to be predictive of clinical events, such as significant plaque on coronary angiography or CT scan (a multivessel coronary disease with two major epicardial arteries having >50% stenosis), or on carotid ultrasound.
\( ^{e} \) Target organ damage is defined as microalbuminuria, retinopathy, or neuropathy.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
3.3. Treatment goals across total cardiovascular disease risk categories
Treatment goals have been defined in accordance with an overall ASCVD risk score determining the 10-year risk of any cardiovascular event [3]. In general, it is accepted that the reduction in low-density lipoprotein cholesterol (LDL-C) levels should persist indefinitely as the reduction is associated with a parallel reduction of ASCVD events. The evidence has not identified a predetermined level of LDL-C below which benefit ceases, or harm supersedes. The purpose of defining targets is to attain the maximum compliance to lipid-lowering management on the part of both the patients and practitioners. As such, it is reasonable to target an LDL-C level that is as low as possible [37–39]. However, individual variations in response to therapy have been reported with ample evidence of residual risk. It is, therefore, imperative to individualize the treatment strategy [40]. Treatment goals across total cardiovascular disease risk categories are presented in Figure 2.
Patients with FH are at high cardiovascular risk, and the treatment goal is LDL cholesterol <1.8 mmol/l or at least a 50 % reduction in LDL cholesterol. However, early detection and prevention of events are the real goals in the management of this high-risk population.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Figure 2. Treatment goals across total cardiovascular disease risk categories applied to the Saudi population
Apo-B = apolipoprotein B; ASCVD= atherosclerotic cardiovascular disease; BMI, body mass index; BP = blood pressure; CKD = chronic kidney disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; FH = familial hypercholesterolemia; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; non-HDL-C = non-high-density lipoprotein cholesterol; SCORE = Systematic Coronary Risk Estimation; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TC = total cholesterol.
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
3.4. Risk factors
The risk factors for ASCVD are age, gender, cholesterol and lipoprotein abnormalities, hypertension, DM, pre-diabetes, insulin resistance, and lifestyle factors (including tobacco use, overweight and obesity, unhealthy diet, limited physical activity, and air pollution) (Figure 3) [4,35,41]. Continuing exposure to risk factors results in further ASCVD progression. Total CVD risk depends on the individual's overall risk-factor profile (Tables 4, 5&6).
Age and gender are main drivers of CVD risk. Women >75 and men >65 years of age are almost always at high 10-year CVD risk [41]. In Saudi Arabia, results from a cross-sectional community-based study covering the whole population from all the 20 health regions of the kingdom aged between 15 and 64 years revealed that TGs and the ratio of total cholesterol (TC)/ High-density lipoprotein cholesterol (HDL-C) were significantly higher in males, while HDL-C and TC were significantly higher in females. No significant differences in LDL-C concentration according to gender were observed (p = 0.341). Moreover, significantly higher dyslipidemia prevalence of TC and TG was found in older subjects [42] (See Supplementary Material; Supplementary Table 1).
LDL-C is highly atherogenic, and the cumulative LDL-C arterial burden is a central determinant for ASCVD initiation and progression. Lowering LDL-C reduces the risk of CV events, and both relative and absolute risk reductions are associated with the magnitude of LDL-C reduction [43]. Assessment of LDL-C is the mainstay component of the management of ASCVD risk [3,44]. Alike, the relationship between non-high-density lipoprotein cholesterol (non-HDL-C), which encompasses all atherogenic, i.e., Apo-B-containing, lipoproteins; and CV risk is at least as strong as the relationship with LDL-C [41]. Apo-B-containing lipoproteins have a central causal role in the initiation and progression of atherosclerosis, and quantitation of Apo-B directly estimates the number of atherogenic
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
particles in plasma [3]. In Saudi Arabia, dyslipidemia is the most prevalent ASCVD risk factor (68.6%) [45], and the prevalent pattern is low HDL-C and high triglycerides (TG) which is different from many other regions in the world. The high prevalence of metabolic syndrome, DM, FH, and consanguineous marriages is the main contributing factor behind this pattern in the kingdom [46,47].
With regards to hypertension, a national survey conducted in the kingdom including 10,735 participants found that 15.2% (17.8% for males and 12.5% for females) and 40.6% were hypertensive or borderline hypertensive, respectively [48]. DM is steadily increasing and rapidly becoming one of the main health issues in Saudi Arabia, with major fear about millions of undiagnosed cases [49]. More than one quarter (25.2%) of the Saudi adult population has diabetes, which is predicted to more than double by 2030. Moreover, the WHO ranks Saudi Arabia second in the prevalence of DM in the Middle East region and seventh in the world [50]. In fact, Saudi Arabia reached a point where DM is considered an epidemic [51]. Atherogenic dyslipidemia is one of the major risk factors for CVD in people with type 2 DM (of which about 50% have elevated TGs or low HDL-C levels) and in people with abdominal obesity and insulin resistance or impaired glucose tolerance [3].
Cigarette smoking prevalence in Saudi Arabia is has shown to be more prevalent in the Northern regions, relatively high in the male population at 32.5%, in particular among those aged between 25 - 44 years old, and 3.9% among females [52]. Heart disease, DM, and hypertension were already present and diagnosed in 5.2%, 12.5%, and 23.2%, respectively, amongst smokers surveyed in that study. Ibrahim Alasqah [53] reported a prevalence of smoking ranging from 12.7% to 39.6% among adolescents regardless of their educational stage. The prevalence amongst female adolescents ranged between 1.6% to 11.1% [54]. Moreover, epidemiological data have shown alarming evidence of high water pipe usage among Saudi teenagers and college students [55].
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
The prevalence of overweight and obesity in the Saudi population across different age groups is high, indicating ineffectiveness or lack of preventive measures (Figure 4) [8]. According to World Atlas data, Saudi Arabia is ranked 12 among obese countries [56]. The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration revealed that both overweight (body mass index (BMI) ≥25 to <30 kg/m²) and obesity (BMI ≥30 kg/m²) were associated with a significantly increased risk of coronary heart disease (CHD) and stroke, compared with normal weight (BMI ≥20 to <25 kg/m²), with 50% of the excess risk of overweight and 44% of the excess risk of obesity for CHD mediated by blood pressure (BP), cholesterol, and glucose [57].
Excessive consumption of caffeinated or carbonated drinks all sweetened with sugar, higher consumption of foods rich in fat, carbohydrates, and salt, and lower consumption of fruits and vegetables amongst the Saudi population are associated with increased risk of dyslipidemia [58]. Moradi-Lakeh et al. conducted a household survey in 2013 in 10,735 Saudi individuals aged ≥15 years. Dietary guideline recommendations were met by only 5.2% of individuals for fruits, 7.5 % for vegetables, 31.4 % for nuts and 44.7 % for fish [59]. The majority of Saudis are not active enough to meet the recommended guidelines for moderate to vigorous physical activity [60]. Females were significantly less active than males in terms of percentages spent more than 1680 metabolic equivalent values (METs \( ^{a} \) )-min/week \( ^{b} \) and more than 2520 METs-min/week \( ^{c} \) (21.9% vs 55.5%, and 12.9% vs 43.5% for Saudi females and males, respectively, p < 0.01) [61]. The prevalence of physical inactivity appears to increase with advancing age. The most important barriers to physical inactivity are the lack of time, followed by lack of appropriate place (especially for females), and lack of facility and
\( ^{a} \) Physical activities were assigned metabolic equivalent (MET) values based on the compendium of physical activity [151] and the compendium of physical activity for youth [152].
\( ^{b} \) = 60 min per day × 7 days/week × 4 METs (moderate-intensity physical activity).
\( ^{c} \) = 60 min per day × 7 days/week × 6 METs (moderate- to vigorous-intensity physical activity)
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
resources. Physical inactivity is significantly associated with obesity and waist circumference in adults, children, and adolescents [60].
Air pollution is a major contributor to the global burden of disease, and accounted for 12% and 20% of all deaths and CVD deaths, respectively in 2019. Further, air pollution was the 4th highest-ranking risk factor for mortality, with more attributable deaths than high LDL-C, high BMI, physical inactivity, or alcohol use [62]. Air pollution is a complex and dynamic mixture of numerous compounds in gaseous and particle form, originating from diverse sources. Particulate matter is responsible for the vast majority of the disease burden via its impact on ischemic heart disease and stroke [63,64]. In Saudi Arabia, several studies have emphasized the association between air pollutants and CVD, as well as the detrimental induction of genes involved in inflammation, lipid metabolism, and atherosclerosis [65,66] (See Supplementary Material; Supplementary Table 1).
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Figure 3. Prevalence of cardiovascular risk factors in Saudi Arabia
*Males.
Adapted from [4,35,41].
Figure 4. Prevalence of obesity in Saudi Arabia stratified by age group
Adapted from [7].
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Table 4. Recommendations for lipid analyses in Saudi Arabia
<table><tr><td>Recommendations</td><td>CORa</td><td>LOEb</td></tr><tr><td>TC, TG, HDL-C, LDL-C, and non-HDL-C are recommended as the primary lipid panel to estimate the risk of ASCVD and to guide therapeutic decision-making.</td><td>I</td><td>C [67]</td></tr><tr><td>LDL-C analysis is recommended as the mainstay component for screening, diagnosis, and management of ASCVD, and LDL-C is recommended as the primary target of lipid-lowering therapies.</td><td>I</td><td>C[43,68–70]</td></tr><tr><td>Apo-B can be measured directly and accurately and better predicts risk under all circumstances than LDL-C or non-HDL-C. If available, Apo-B analysis may be used as an alternative to LDL-C as the primary measurement for screening, diagnosis, and management.</td><td>IIb</td><td>C [71]</td></tr><tr><td>Apo-B analysis should be considered over LDL-C or non-HDL-C for risk assessment in patients with high TG levels, DM, obesity, metabolic syndrome, or very low LDL-C levels.</td><td>IIa</td><td>C [71]</td></tr><tr><td>Lp(a) should be considered for ASCVD risk estimation at least once in each adult person's lifetime, especially in patients with premature ASCVDc, family history of premature ASCVD, and/or elevated Lp(a), FH, recurrent ASCVD despite optimal lipid-lowering treatment.</td><td>IIa</td><td>C [72]</td></tr><tr><td>Non-fasting/random lipid sampling may be used for screening purposes. An alternative approach is to measure the random non-HDL-C for convenience and better prediction.</td><td>IIb</td><td>B [73]</td></tr><tr><td>Fasting lipid profile is recommended to confirm the diagnosis and for further monitoring.</td><td>I</td><td>B [73]</td></tr></table>
ASCVD= atherosclerotic cardiovascular disease; DM = diabetes mellitus; FH = familial hypercholesterolaemia; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein(a); non-HDL-C = non-high-density lipoprotein cholesterol; TC = total cholesterol; TG = triglycerides.
\( ^{a} \) Class of recommendation
\( ^{b} \) Level of evidence
\( ^{c} \) Men <55 years, women <60 years
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
Table 5. Recommendations for treatment goals for LDL-C in Saudi Arabia
<table><tr><td>Recommendations</td><td>CORa</td><td>LOEb</td></tr><tr><td>In secondary prevention for patients at very-high risk, an LDL-C reduction of >_50% from \( baseline^c \) and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended</td><td>I</td><td>A[68,74–77]</td></tr><tr><td>In primary prevention for individuals at very-high risk but without FH, an LDL-C reduction of >_50% from baselined and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended</td><td>I</td><td>C[68,75,78]</td></tr><tr><td>In primary prevention for individuals with FH at very-high risk, an LDL-C reduction of >_50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) is recommended.</td><td>I</td><td>C [3]</td></tr><tr><td>For patients with ASCVD who experience a second vascular event within 2 years (not necessarily of the same type as the first event) while taking maximally tolerated statin-based therapy are considered at extremely high risk, and an LDL-C goal of <1.0 mmol/L (<40 mg/dL) is recommended.</td><td>I</td><td>B [5,76,77]</td></tr><tr><td>In patients at high risk, an LDL-C reduction of >_50% from baselined and an LDL-C goal of <1.8 mmol/L (<70 mg/dL) are recommended.</td><td>I</td><td>A[68,75]</td></tr><tr><td>In individuals at moderate risk, an LDL-C goal of <2.6 mmol/L (<100 mg/dL) is recommended.</td><td>I</td><td>A [75]</td></tr><tr><td>In individuals at low risk, an LDL-C goal <3.0 mmol/L (<116 mg/dL) should be considered.</td><td>IIa</td><td>A [78]</td></tr></table>
ASCVD= atherosclerotic cardiovascular disease; FH = familial hypercholesterolemia; LDL-C = low-density lipoprotein cholesterol.
\( ^{a} \) Class of recommendation
\( ^{b} \) Level of evidence
\( ^{c} \) The term ‘baseline’ refers to the LDL-C level in a person not taking any LDL-C-lowering medication. In people who are taking LDL-C-lowering medication(s), the projected baseline (untreated) LDL-C levels should be estimated, based on the average LDL-C-lowering efficacy of the given medication or combination of medications.
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
Table 6. Goals for cardiovascular disease prevention in Saudi Arabia
<table><tr><td>Parameter</td><td>Goal</td></tr><tr><td>LDL-C</td><td>Recurrent events (extremely high-risk); an LDL-C goal of <1 mmol/L (<40 mg/dL).Very-high-risk in primary or secondary prevention; an LDL-C reduction of ≥50% from baseline and an LDL-C goal of <1.4 mmol/L (<55 mg/dL) are recommended.High-risk; a therapeutic regimen that achieves ≥50% LDL-C reduction from baseline and an LDL-C goal of <1.8 mmol/L (<70 mg/dL).Moderate-risk; an LDL-C goal of <2.6 mmol/L (<100 mg/dL).Low-risk; an LDL-C goal of <3.0 mmol/L (<116 mg/dL).</td></tr><tr><td>Non-HDL-C</td><td>Recurrent events (extremely high-risk); a non-HDL-C goal of <1.8 mmol/L (<70 mg/dL).Very-high-risk in primary or secondary prevention; a non-HDL-C goal of <2.2 mmol/L (<85 mg/dL) are recommended.High-risk; a non-HDL-C goal of <2.6 mmol/L (<100 mg/dL).Moderate-risk; a non-HDL-C goal of <3.4 mmol/L (<130 mg/dL).</td></tr><tr><td>Apo-B</td><td>Recurrent events (extremely high-risk); an Apo-B goal of <55 mg/dL.Very-high risk in primary or secondary prevention; an Apo-B goal of <65 mg/dL.High-risk; an Apo-B goal of <80 mg/dL.Moderate-risk; an Apo-B goal of <100 mg/dL.</td></tr><tr><td>TG</td><td>No goal, but <1.7 mmol/L (<150 mg/dL) indicates lower risk, and higher levels indicate a need to look for other risk factors.</td></tr><tr><td>Blood pressure</td><td><140/90 mmHg.</td></tr><tr><td>DM</td><td>HbA1c <7% (<53 mmol/mol).</td></tr><tr><td>Tobacco usea</td><td>No exposure to tobacco in any form</td></tr><tr><td>Body weight</td><td>BMI 20-25 kg/m2, waist circumference <94 cm (men) and <80 cm (women).</td></tr><tr><td>Diet</td><td>A healthy diet low in saturated fat with a focus on wholegrain products, nuts, vegetables, lean vegetable or animal protein, and fish, and minimizes the intake of trans fats, red meat and processed red meats, refined carbohydrates, and sweetened beverages.</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجاب الصحي السعودي
Saudi Health Council
[Non-Text]
Physical activity
- 3.5-7 h moderately vigorous physical activity per week or 30-60 min most days.
Adapted from [3,35]
\( ^{a} \) This includes all types of tobacco products such as cigarettes, cigars, shisha, electronic cigarettes, etc., as well as smokeless tobacco use (e.g., chewing tobacco) and secondhand smoke.
BMI, body mass index; CV = cardiovascular; CVD = cardiovascular disease; DM = diabetes mellitus; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; non-HDL-C = non-high-density lipoprotein cholesterol; TG = triglycerides.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
3.5. Risk enhancers
Risk enhancing factors are independent of other risk associated with ASCVD. Assessing for risk-enhancing factors can help guide decisions about preventive interventions in adults at borderline or intermediate risk and to adjust the intensity of LDL-lowering therapy (Table 7) [4,35]. Family history of premature ASCVD (males, age <55 y; females, age <60 y) is a risk-enhancing factor that should be considered for clinician-patient risk discussion (See Table 10; Recommendations for FH management in Saudi Arabia). Metabolic syndrome, another risk enhancer, is characterized by the clustering of central obesity, dyslipidemia, elevated BP, and hyperglycemia [35]. A large cross-sectional study that included 12,126 Saudi subjects reported a high prevalence of metabolic syndrome in Saudi Arabia that equals 39.8% (34.4% in men and 29.2% in women). The most frequently observed component of metabolic syndrome was low levels of HDL-C, followed by abdominal obesity [79]. Despite patients with metabolic syndrome being classified as high-risk, precise figures about its prevalence and response to treatment in Saudi Arabia are still lacking [80].
CKD is an important disorder worldwide that affects more than 10% of adults and increases the risk of many adverse outcomes; among them, CVD is particularly important. As CKD progresses, kidney-specific risk factors for CV events and disease come into play and ultimately increase the risk for CVD. Moreover, raised concentrations of albumin in urine and impaired kidney function increase the risk of CVD by 2 to 4 times. CVD is the leading cause of death in persons with CKD [81,82]. In Saudi Arabia, adequate epidemiological data about CKD is lacking. However, figures from a pilot community-based screening program in 2010 concluded that the prevalence of CKD is around 5.7% in Riyadh city [83].
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Table 7. ASCVD risk-enhancing factors, cut-off values/conditions, and recommendations in Saudi Arabia
<table><tr><td>Risk-enhancing factors and the corresponding cut-off values/conditions</td><td>Cut-off values/conditions</td><td>Recommendations</td><td>CORa</td><td>LOEb</td></tr><tr><td>Metabolic syndrome*</td><td>Increased waist circumferenceElevated TG >150 mg/dL, non-fastingElevated BP (≥130/85 mm Hg)Elevated fasting glucose (≥110 mg/dL)Low HDL-C <40 mg/dL in men; <50 mg/dL in women</td><td>Counseling and comprehensive lifestyle interventions, including calorie restriction and adjunctive therapies, are recommended to reduce waist circumference and improve the cardio-metabolic risk profiles.</td><td>I</td><td>B[35,84,85]</td></tr><tr><td>CKD</td><td>eGFR 15–59 mL/min/1.73 m2 with or without albuminuria; not treated with dialysis or kidney transplantation</td><td>Patients with Kidney Disease Outcomes Quality Initiative stage 3-5c CKD are recommended to be managed as the high or very-high risk of ASCVD.</td><td>I</td><td>A [3]</td></tr><tr><td rowspan="2">Elevated high-sensitivity C-reactive protein</td><td rowspan="2">≥2.0 mg/L</td><td>The high-sensitivity C-reactive protein diagnostic test is recommended to detect very low levels of C-reactive protein and thereby enable a more accurate and precise measure of chronic inflammation compared with standard C-reactive protein.</td><td>I</td><td>A [86]</td></tr><tr><td>In adults 40 to 75 years of age without DM and at intermediate risk, high-sensitivity C-reactive protein ≥2.0 mg/L is associated with increased ASCVD risk and should favor initiation of lipid-lowering therapy.</td><td>IIa</td><td>A [4]</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
<table><tr><td>History of premature menopause</td><td>Age <40 y</td><td rowspan="2">Clinicians should consider conditions specific to women when discussing lifestyle intervention and the potential for the benefit of therapy</td><td rowspan="2">IIa</td><td rowspan="2">B [4]</td></tr><tr><td>History of pregnancy-associated conditions that increase later ASCVD risk</td><td>Such as hypertension, preeclampsia, gestational DM</td></tr><tr><td>Persistently elevated* primary hypertriglyceridemia</td><td>≥175 mg/dL, non-fasting</td><td>Clinicians should address and treat lifestyle factors (obesity and metabolic syndrome), secondary factors (ex. DM, chronic liver disease or CKD, hypothyroidism), or medications that increase triglycerides.</td><td>IIa</td><td>B [4]</td></tr><tr><td>Primary hypercholesterolemia*</td><td>LDL-C, 160–189 mg/dL (4.1–4.8 mmol/L)Non-HDL-C 190–219 mg/dL (4.9–5.6 mmol/L)</td><td>In intermediate-risk patients; LDL-C levels should be reduced by 30% or more.In high-risk patients; levels should be reduced by 50% or more.</td><td>IIa</td><td>B [4]</td></tr><tr><td rowspan="2">Chronic inflammatory conditions</td><td rowspan="2">Such as RA, lupus, psoriasis, or HIV/AIDS</td><td>In patients with chronic inflammatory disorders or HIV, a fasting lipid profile and assessment of ASCVD risk factors before and 4 - 12 weeks after starting inflammatory disease-modifying therapy or antiretroviral therapy may be useful as a guide to benefit and for monitoring lipid-lowering drug therapy.</td><td>IIb</td><td>B [4]</td></tr><tr><td>In adults with RA, it may be useful to recheck lipid values and other major ASCVD risk factors 2 - 4 months after</td><td>IIb</td><td>B [4]</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
controlling the patient's inflammatory disease.
AIDS = acquired immunodeficiency syndrome; Apo-B = apolipoprotein B; ASCVD, atherosclerotic cardiovascular disease; BP = blood pressure; CKD = chronic kidney disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; HDL-C = high-density lipoprotein cholesterol; HIV = human immunodeficiency virus; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein (a); non-HDL-C = non-high-density lipoprotein cholesterol; RA = rheumatoid arthritis, TG = triglycerides.
*Optimally, 3 determinations
\( ^{a} \) Class of recommendation
\( ^{b} \) Level of evidence
\( ^{c} \) Defined as eGFR < 60ml/min/1.73m \( ^{2} \) on two measurements more than 3 months apart.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
3.6. Risk modifiers
Risk modifiers are additional risk factors or individual information that can modify the calculated risk. Assessment of risk modifiers is particularly relevant if the individual's risk is close to a decision threshold (i.e., in low-risk or very-high-risk situations, additional information is less likely to alter management decisions) (Table 8) [41].
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
Table 8. ASCVD risk modifiers, cut-off values/conditions, and recommendations in Saudi Arabia
<table><tr><td>Risk Modifier</td><td>Cut-off values/conditions</td><td>Recommendations</td><td>CORa</td><td>LOEb</td></tr><tr><td>Coronary artery calcium (CAC) scoring*</td><td>In asymptomatic individuals with low or moderate risk, the presence of a CAC score >100 Agatston, and carotid or femoral plaque burden on ultrasonography may reclassify them to a higher risk category.</td><td>CAC score assessment with CT should be considered in individuals at low or moderate risk in whom the respective LDL-C goal is not achieved with lifestyle intervention alone.</td><td>IIa</td><td>B [3]</td></tr><tr><td>Arterial (carotid and/or femoral) plaque burden on arterial ultrasonography</td><td>Assessment of carotid or femoral plaque burden with ultrasound is predictive of CV events.</td><td>Arterial (carotid and/or femoral) plaque burden on arterial ultrasonography should be considered as a risk modifier in individuals at low or moderate risk.</td><td>IIa</td><td>B [87]</td></tr><tr><td>Psychosocial stress</td><td>Stress symptoms and psychosocial stressors modify CVD risk and are associated in a dose-response pattern with the development and progression of ASCVD.</td><td>Physicians should be equally attentive to somatic as to emotional causes of symptoms.Assessment of psychosocial stressors should be considered (RRs are commonly between 1.2 and 2.0).</td><td>IIa</td><td>B [65,66]</td></tr><tr><td>Socioeconomic determinants</td><td>Socioeconomic inequalities are strong determinants of CVD risk. Low socioeconomic status and work stress are independently associated with ASCVD development and prognosis in both sexes.</td><td>Clinicians should tailor advice to a patient's socioeconomic and educational status, as well as cultural, work, and home environments</td><td>IIa</td><td>A [35,41,88,89]</td></tr></table>
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
<table><tr><td>Ethnicity</td><td>Considerable variability in ASCVD risk factors exists between different ethnic groups.</td><td>No single CVD risk score performs adequately in all groups. Thus, the use of a multiplying factor may be helpful to take account of CVD risk imposed by ethnicity independent of other risk factors.</td><td>IIb</td><td>A [41]</td></tr></table>
ASCVD= atherosclerotic cardiovascular disease; CAC = coronary artery calcium; CT = computed tomography; CV = cardiovascular; CVD = cardiovascular disease; LDL-C = low-density lipoprotein cholesterol; RR = relative risk.
*CAC score is increased following statin treatment; therefore, the CAC scores of statin-treated patients should be interpreted with caution.
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المركز الوطني للقلب
National Heart Center
المجلب الصحي السعودي
Saudi Health Council
[Non-Text]
3.7. COVID-19 and cardiovascular disease
The CV complications of acute coronavirus disease 2019 (COVID-19) are well reported in several studies [90–94]. A recent study by Xie and colleagues [95] used databases of 153,760 individuals with COVID-19 infection, 5,637,647 individuals as contemporary controls, and 5,859,411 individuals as historical controls to estimate risks and 1-year burdens of CV outcomes. The results revealed that individuals with COVID-19 are at increased risk of incident CV disease categories including ischemic and non-ischemic heart disease, myocarditis, pericarditis, dysrhythmias, heart failure, thromboembolic disease, and cerebrovascular disorders beyond the first 30 days after infection. These risks were evident among all individuals, whether hospitalized or not during the acute phase of the COVID-19 infection. These results flagged the evidence that CV disease risk and 1-year burden in survivors of acute COVID-19 are substantial, and care of those survivors should include attention to CV disease.
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
4. Management of Dyslipidemia in different clinical settings
Aggressive lipid management has been demonstrated to improve cardiovascular outcomes in specific clinical settings such as ACS and other very high-risk entities, namely diabetes, CKD, and FH (Table 9).
4.1. Acute coronary syndromes
With respect to ACS, intensive statin therapy early after a clinical event can reduce future events permitting a significant early pleiotropic effect. Randomized evidence has unequivocally demonstrated benefit with early initiation of treatment, that is, in-hospital and continued long-term [96–99]. Furthermore, high-intensity statin therapy in all patients with ACS is recommended irrespective of the baseline LDL-C values. Immediately after an ACS, it is well known that LDL levels will drop; therefore, ideally, assays should be drawn within the first twenty-four hours [100]. Assays prior to the event are more reliable. The recommended target for LDL-C is a 50% reduction and a level of <1.4 mmol/L (<55 mg/dL). For individuals suffering recurrent events (even in a different territory) within 2 years, a goal of <1.0 mmol/L (<40 mg/dL) for LDL-C is recommended. For very high-risk patients, the first-line treatment strategy is recommended to include high-intensity statin in combination with ezetimibe. If the target is not reached, the addition of PCSK9 monoclonal antibodies is recommended. For the extremely*high-risk patients, initiation of triple combination therapy should be considered as the first-line approach [5,74,77,101]. These agents achieve a sustained reduction in all subgroups and permit a reduction in all events, including cerebrovascular, rehospitalizations, and all-cause death.
*Extremely high risk = post ACS + history of other vascular event/peripheral artery disease/ polyvascular disease/ multivessel coronary artery disease/familial hypercholesterolemia
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
4.2. Diabetes mellitus
DM is often referred to as an ASCVD equivalent. It confers an independent risk for multiple cardiovascular disorders that is double other factors [102]. Fasting blood glucose has a log-linear correlation with the risk of vascular disease at all concentrations, including below 7 mmol/L, i.e., below the threshold for diabetes. Those with end-organ damage, such as retinopathy and nephropathy, and microvascular dysfunction have a higher risk of cardiovascular events. Additional risk factors render diabetics at even higher risk of cardiovascular events. Diabetics with concomitant coronary artery disease have a significantly worse prognosis and survival after an ACS [103]. Optimal dosing, escalation, and lipid management are critical. Although data suggests a higher risk of development of new-onset diabetes with statin therapy, the majority occur in the subset with prediabetes. The magnitude of the absolute reduction of LDL-C levels and, consequently cardiovascular events, suggest intensive therapy should be encouraged and outweighs any potential risk of new-onset diabetes [104–106].
Of note, data extracted from the Odyssey and Fourier studies revealed no increase in the risk of new-onset diabetes with the use of PCSK9 monoclonal antibodies \( [76,77] \) . In their metanalysis, de Carvalho and colleagues reported an increase in fasting blood glucose and glycated hemoglobin (HbA1c) levels in 68,123 patients who were taking concomitant statins and PCSK9 monoclonal antibodies; however, this did not result in a higher incidence of type 2 diabetes. Furthermore, the analysis only included short-term follow-up. The sub-analysis of the landmark Odyssey trial did not observe conversion to diabetes with these agents \( [77,107] \) .
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المركز الوطني للقلب
National Heart Center
المجلس الصحي السعودي
Saudi Health Council
[Non-Text]
4.3. Chronic kidney disease
CKD stage 3 is considered high, and stage 4-5 is considered a very-high risk. An estimated glomerular filtration rate of less than 60 mL/min/1.73 m² and an albumin creatinine ration of 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality. Therefore, a high-intensity statin is recommended in those with adjunctive risk, established ASCVD, or presenting with an ACS to achieve the maximum reduction [82]. Although adverse events with statin therapy require monitoring, appropriate intensity is advisable as this population has an overall higher risk of cardiovascular events in patients with CKD [108]. In addition, in patients with CKD presenting with acute coronary syndromes, PCSK9 monoclonal antibodies were associated with lower incidence of ASCVD events and all-cause death across all ranges of dysfunction. In fact,
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