|Year : 2016 | Volume
| Issue : 2 | Page : 88-93
Factors associated with worse control of hypercholesterolemia in Saudi patients: Subanalysis of the Centralized Pan-middle East Survey on the undertreatment of hypercholesterolemia
Khalid Alnemer1, Ibrahim Alhomood2, Omalkhaire Alshaikh1, Mohammed Arafah3, Faisal Alanazi4, Shorook Alherz5, Wael Al Mahmeed6, Abdullah Shehab7, Omer Al Tamimi8, Mahmoud Alawadhi9, Ali T Al-Hinai10
1 Department of Medicine, School of Medicine, Al-Imam Muhammad Ibn Saud Islamic University, Riyadh, Saudi Arabia
2 Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
3 Department of Cardiology, King Saud University, Riyadh, Saudi Arabia
4 Department of Noncommunicable Diseases, Ministry of Health, Riyadh, Saudi Arabia
5 Department of Family Medicine, National Guard Hospital, Riyadh, Saudi Arabia
6 Department of Cardiology, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
7 Department of Internal Medicine, United Arab Emirates University, Abu Dhabi, United Arab Emirates
8 Department of Medicine, Hamad Medical Corporation, Doha, Qatar
9 Department of Endocrinology, Al Amiri Hospital, Kuwait
10 Department of Medicine, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman
|Date of Submission||26-May-2016|
|Date of Acceptance||08-May-2017|
|Date of Web Publication||21-Aug-2017|
Department of Medicine, School of Medicine, Al-Imam Muhammad Ibn Saud Islamic University, Riyadh
Source of Support: None, Conflict of Interest: None
Background: A subanalysis of the Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia (CEPHEUS) was done to establish the factors associated with worse control of hypercholesterolemia (HC) in Saudi Arabia.
Methods and Results: CEPHEUS (NCT01031277) was a multicenter survey conducted in six Middle Eastern countries (Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman) between November 2009 and July 2010. Male and female patients aged ≥18 years on lipid-lowering drugs for ≥3 months (stable medication for ≥6 weeks) were recruited. At the study visit, investigators completed a questionnaire (experience and perception of the management of HC), patients completed a questionnaire (awareness of HC, current treatment schedule and perception, compliance), and patient fasting serum samples were collected to measure lipid profile. For the purpose of this subanalysis, patients were categorized as Saudi or non-Saudi. Multivariate analysis of the data showed that diabetes, obesity, and high waist circumference are associated with worse control of HC in Saudi Arabia. The lipid profile showed worse control of all variables except high-density lipoprotein-cholesterol. Saudi patients on statins and fibrates for primary prevention were the highest low-density lipoprotein-cholesterol (LDL-C) goal achievers. The positive predictors of achievement of LDL-C goals are age <40 years, absence of diabetes mellitus, nonsmoking status, compliance to medication, and glycated hemoglobin (HbA1c) <8%.
Conclusion: This subanalysis establishes that diabetes, obesity, and high waist circumference age >40 years, smoking, HbA1c >8% are associated with worse control of HC in Saudi Arabia.
Keywords: Cardiovascular disease, Centralized Pan-Middle East Survey on the undertreatment of hypercholesterolemia, hypercholesterolemia, Saudi, subanalysis
|How to cite this article:|
Alnemer K, Alhomood I, Alshaikh O, Arafah M, Alanazi F, Alherz S, Al Mahmeed W, Shehab A, Al Tamimi O, Alawadhi M, Al-Hinai AT. Factors associated with worse control of hypercholesterolemia in Saudi patients: Subanalysis of the Centralized Pan-middle East Survey on the undertreatment of hypercholesterolemia. Imam J Appl Sci 2016;1:88-93
|How to cite this URL:|
Alnemer K, Alhomood I, Alshaikh O, Arafah M, Alanazi F, Alherz S, Al Mahmeed W, Shehab A, Al Tamimi O, Alawadhi M, Al-Hinai AT. Factors associated with worse control of hypercholesterolemia in Saudi patients: Subanalysis of the Centralized Pan-middle East Survey on the undertreatment of hypercholesterolemia. Imam J Appl Sci [serial online] 2016 [cited 2019 Sep 19];1:88-93. Available from: http://www.e-ijas.org/text.asp?2016/1/2/88/213389
| Introduction|| |
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for 17.3 million deaths annually, and the incidence of CVD is expected to rise to 25 million by 2030. A study from the Middle Eastern countries reports that the rate of increase in CVD-associated mortalities is one of the highest in the world. In the Middle East region, the CVD mortality rate per 100,000 population is the highest in Saudi Arabia (338.1), followed by the United Arab Emirates (297.6), Oman (244.9), Kuwait (239.0), Bahrain (187.2), and Qatar (157.0). The Global Burden of Disease 2010 study estimated that high cholesterol accounted for about 5.14% of total deaths, 3.96% of years of life lost, and 1.99% of disability-adjusted life-years in Saudi Arabia. The prevalence of hypercholesterolemia (HC) in Saudi Arabia was reported as 18.6% for men and 19.7% for women in 2005. A recent study in 2013 has shown that about 8% of Saudis have HC, and 700,000 of them are unaware of their condition that can be controlled through early detection campaigns, lifestyle change, and medication to avoid disease progression toward more serious stages. The cause for increased CVD in Saudi Arabia is attributed to lifestyle changes accompanied by several CVD-risk factors which include smoking, eating high fat and low-fiber diets, increased waist-to-hip ratio, and increased blood cholesterol and sugar. Statins have proved to be beneficial in the primary and secondary prevention of CVDs. The National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) III guidelines recommend the primary prevention with statins for low-density lipoprotein-cholesterol (LDL-C) level ≥190 mg/dl (∼5.0 mmol/L). A 2004 update to the NCEP ATP III guidelines on cholesterol management sets a LDL-C goal of <100 mg/dl (<2.6 mmol/l) for high-risk patients (those with coronary heart disease [CHD] equivalents) and recommends an optional therapeutic target of LDL-C <70 mg/dl (<1.8 mmol/l) in very high-risk patients (those with acute coronary syndrome or those with CHD plus diabetes, metabolic syndrome, multiple risk factors, or a poorly controlled risk factor [e.g., continued smoking]).,
Epidemiological surveys have shown that elevated total serum cholesterol and elevated LDL-C levels are strongly correlated with CHD risk. This relationship has been observed in many populations throughout the world.,,
The Centralized Pan-Middle East Survey on the Undertreatment of HC (CEPHEUS) was initiated to quantify the degree of undertreatment of HC in the Middle Eastern countries. Its primary objective was to establish the proportion of lipid-lowering drug (LLD)-treated patients reaching the LDL-C goals according to the NCEP ATP III and updated 2004 NCEP ATP III guidelines. Secondary objectives-targeted subgroups of primary or secondary prevention patients, those with the metabolic syndrome; and LLD-treated patients reaching the nonhigh-density lipoprotein-cholesterol (HDL-C) goals according to the NCEP ATP III and updated 2004 NCEP ATP III guidelines. Furthermore, CEPHEUS also aimed at the identification of determinants for undertreatment of HC.
The results show that despite the knowledge of the risk of mortality, existing guidelines to reduce this risk, and the use of LLDs, HC remains undertreated in Middle Eastern countries, including Saudi Arabia. Thus, the present subanalysis was conducted to identify the factors associated with worse control of HC in Saudi Arabia.
| Materials and Methods|| |
CEPHEUS (NCT01031277) was a multicenter survey of patients on LLD that recruited 5457 patients across 500 sites in six Middle Eastern countries (Saudi Arabia, United Arab Emirates, Kuwait, Qatar, Bahrain, and Oman) between 22 November 2009 and 07 July 2010.
There was only one visit in this study. Before this visit, all investigators completed a questionnaire based on their experience and perception of the management of HC in their patients. At the study visit, patients were first asked to complete a questionnaire regarding their awareness of HC, their current treatment schedule and perception, and their compliance. Following this, the investigators collected the patients' demographic characteristics, known cardiovascular risk factors, cardiovascular medical history, and current LLD and the reason for the current therapy on a patient record form. In addition, fasting blood samples were taken for total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein (apo) B, apo A-1, fasting blood glucose, and glycated hemoglobin (HbA1c) levels.
Male and female patients aged ≥18 years on LLD for at least 3 months, with no dose change for a minimum of 6 weeks, who signed the informed consent were enrolled into CEPHEUS.
The primary outcomes of this subanalysis were:
- To establish the proportion of patients on LLD reaching the LDL-C goals according to the NCEP ATP III and updated 2004 NCEP ATP III guidelines, in Saudi versus non-Saudi patients
- To establish the proportion of patients on LLD reaching the LDL-C goals according to the NCEP ATP III and updated 2004 NCEP ATP III guidelines in primary/secondary prevention patients and patients with metabolic syndrome
- To identify factors associated with worse control of HC in Saudi versus non-Saudi patients.
SPSS Statistics software, version 17.0 (IBM Corporation, Somers, NY, USA), was used to analyze data. Continuous data are presented as mean (standard deviation). Categorical data are presented as number (percentage). For continuous variables of normal distribution and homogeneous variances, the Student's t- test was used. The Chi-squared test was used for cross–tabulation of qualitative variables in bivariate analysis; when the expected values within cells were <5, the Fisher's exact test was used. In all analyses, P < 0.05 was considered statistically significant. A backward stepwise likelihood ratio logistic regression was performed to determine the positive predictors for the achievement of LDL-C goals in Saudi patients.
| Results|| |
A total of 5457 patients gave their consent to participate in the study and were categorized as Saudi or non-Saudi for the purpose of this subanalysis.
[Table 1] showed that in the Saudi group, patient factors associated with worse control of HC (i.e., odds ratio [OR] >1 and P < 0.05) were diabetes (OR = 2.46 [2.19–2.76]; P < 0.001), obesity (P < 0.001, OR = 1.81 [1.62–2.03]), and high waist circumference (OR = 2.27 [2.03–2.55]; P < 0.001).
|Table 1: Demographic and clinical data in Saudi and non-Saudi population|
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The lipid profile of Saudi versus non-Saudi patients is presented in [Table 2]. Patients in the Saudi group showed increased mean for all variables except HDL-C, indicating a significantly worse control of all variables in the Saudi group.
|Table 2: Lipid profile of Saudi versus non-Saudi patients at the time of the survey|
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The NCEP ATP III risk category of patients enrolled in CEPHEUS was determined programmatically according to updated 2004 NCEP ATP III guidelines as overall, very high risk, high risk, intermediate, and low risk. [Figure 1] shows that in the Saudi group a low percentage (27.4%) of very high-risk patients reached their LDL-C goals and had worse control of HC compared with intermediate (84.1%) and low-risk patients (90.4%). Similar results were observed in the non-Saudi group indicating that higher risk category results in worse control of HC.
|Figure 1: Proportion of Saudi versus non-Saudi patients attaining their 2004 updated National Cholesterol Education Program Adult Treatment Panel III–recommended low-density lipoprotein- cholesterol goals, according to the risk category. *The difference is statistically significant and P = 0.004. Low-risk: P = 0.64; High-risk: P =0.58; Medium high-risk: P = 0.58; Medium low-risk: P = 0.16; Overall: P = 0.22|
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[Figure 2] shows that the percentage of patients reaching the LDL-C goals was highest among patients in primary prevention in both Saudi and non-Saudi groups. The percentage of patients reaching the LDL-C goals was lower in Saudi versus non-Saudi group: primary prevention (57.1% vs. 58.7%), secondary prevention (33.4% vs. 38.2%), familial HC (43.5% vs. 52.9%), metabolic syndrome (46.4% vs. 44.3%), and peripheral artery disease (20.6% vs. 26.3%).
|Figure 2: Attainment of low-density lipoprotein-cholesterol goals in the overall cohort, and in patients with primary and secondary prevention, metabolic syndrome, familial hypercholesterolemia, and peripheral arterial disease. Primary prevention P = 0.35; Secondary prevention: P = 0.062; Familial hypercholesterolemia (FH): P = 0.50; Metabolic syndrome: 0.33; Peripheral artery disease: P = 0.42|
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[Figure 3] shows that the percentage of patients attaining the LDL-C goals overall was higher in Saudi group compared with non-Saudi group (52.4% vs. 50.7%). In Saudi group, the percentage of patients attaining the LDL-C goals were the highest in those on statins + fibrates (55.7%), followed by statins + other LLD (52.6%), only statins (52.4%), other LLD (50%), and only fibrates (34.8%). In non-Saudi group, the percentage of patients attaining the LDL-C goals were the highest in those on only statins (50.9%), followed by statins + fibrates (50%), fibrates (47.8%), statins + other LLD (47.7%), and other LLD (30.4%).
|Figure 3: Proportion of patients attaining the National Cholesterol Education Program Adult Treatment Panel III goals stratified by the lipid-lowering drug (ezetimibe, bile acid sequestrant, and nicotinic acid). Statins: P = 0.29; Fibrates: P = 0.37; Statins + fibrates: P = 0.52; Statin + other lipid-lowering drug: P = 0.63; Other lipid-lowering drug: P = 0.58|
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[Figure 4] shows that the positive predictors for achievement of LDL-C goals in Saudi patients according to NCEP ATP III guidelines are age <40 years (OR: 1.95, 95% confidence interval [CI]: 1.7–2.25), absence of diabetes mellitus (OR: 1.57, 95% CI: 1.13–2.16), nonsmoking status (OR: 1.63, 95% CI: 1.1–2.43), compliance to medication (OR: 1.42, 95% CI: 1.11–1.83), and HbA1c <8% (OR: 1.45, 95% CI: 1.09–1.94). Metabolic syndrome (OR = 0.76, 0.63–0.94), CVD (OR = 0.79, 0.62–0.99), and coronary artery disease (OR = 0.35, 0.11–0.44) were negatively associated with attaining LDL-C goals.
|Figure 4: Positive predictors for achievement of low-density lipoprotein-cholesterol goals in Saudi patients according to National Cholesterol Education Program Adult Treatment Panel III guidelines. DM: Diabetes mellitus; HbA1c: Glycated hemoglobin|
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| Discussion|| |
The CEPHEUS study confirms the association between increased risk of CVD and increased serum total cholesterol levels. In an effort to reduce both mortality and morbidity associated with CVD, most practice guidelines focus on LDL-C as the primary target for CVD management. The guidelines suggest treating HC based on risk profile (low risk and high risk). Currently available lipid-modifying drugs include bile acid sequestrants, fibrates, nicotinic acid, cholesterol absorption inhibitors, and statins. Of these, statins are the most widely used for the primary and secondary prevention of CVD. Despite this, a large proportion of the Middle Eastern patients on LLDs is not at recommended lipoprotein targets and remains at a substantial residual risk for CVD.
This subanalysis of CEPHEUS has identified diabetes, obesity, and high waist circumference as the factors associated with worse control of HC in Saudi Arabia. The adoption of the Western lifestyle, characterized by decreased physical activity high caloric intake and low consumption of fruits and vegetables in Saudi Arabia over the last thirty has contributed to most of the risk factors of HC. Epidemiological studies have shown high rates of obesity across all segments of the Saudi population and a strong association among obesity and diabetes, HC, and hypertension.,,
Smoking was not associated with worse control of HC since smoking is behavior is associated with weight. Studies have shown that smokers were less likely to be overweight and obese than those who have never smoked. Thus, an apparent overall protective effect of smoking was observed in the Saudi smokers.
The prevalence of HC in Saudi Arabia is lower than the prevalence in European or North American communities, which is due to the young nature of the Saudi population. The prevalence of HC is likely to increase in the near future with the increase in the percentage of the aged population in the community.,
The lipid profile showed worse control of all variables except HDL. Saudi patients in the very–high-risk category were the lowest attainers of LDL-C goals. Saudi patients on statins + fibrates for primary prevention were the highest attainers of LDL-C goals. This suggests a strong relationship between very-high-risk profile and worse control of HC.
Statins are widely prescribed for the primary and secondary prevention of CVD in Saudi Arabia. Intercontinental Marketing Services data in Saudi Arabia shows that 1,128,000 patients were treated with statins: 80% for primary prevention and 20% for secondary prevention. CEPHEUS showed that 71.5% patients were treated for primary prevention and 27.2% for secondary prevention of CVD. This explains the lag in the achievement of LDL-C goals in the secondary prevention versus the primary prevention patients in Saudi Arabia.
The positive predictors for achievement of LDL-C goals in Saudi patients as per NCEP ATPIII guidelines are age <40 years, absence of diabetes mellitus, nonsmoking status, compliance with medication, and HbA1c <8%.
Patient compliance with therapy is associated with the achievement of LDL-C targets. Results of CEPHEUS have shown that forgetting to take medication was the major reason for noncompliance in the Middle Eastern region, which is in-line with other studies worldwide. Nonadherence to statin therapy is a significant factor for HC being undertreated.,
Increased awareness of the results of nonadherence, including safer prescribing, improvement in physician-patient alliance and reduction in drug costs, will enhance the cost-effectiveness of the use of statins and significantly improve patient care and outcomes.
Studies have shown that there is an increasing prevalence of HC in Saudi Arabia and the majority of them are unaware of their condition, thus HC remains undertreated. There is a need for a national program to increase awareness about health hazards of HC and the need for early diagnosis among the Saudi population. Screening for HC should be prioritized in the elderly and individuals with comorbidities (e.g., diabetes, hypertension) who are at higher risk of serious health complications, with emphasis on controlling weight, and periodic cholesterol measurement.
| Conclusion|| |
This subanalysis establishes that diabetes, obesity, and high waist circumference age >40 years, smoking, and HbA1c >8% are associated with worse control of HC in Saudi Arabia.
All authors fulfill the International Committee of Medical Journal Editors requirements for authorship of this manuscript and have read approved the final manuscript for publication. The authors thank Clinart Middle East and North Africa for providing statistical analysis and writing assistance.
Financial support and sponsorship
The authors received funding support from Astra Zeneca for their research and preparation of this manuscript.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ramahi TM. Cardiovascular disease in the Asia Middle East region: Global trends and local implications. Asia Pac J Public Health 2010;22 3 Suppl: 83S-9S.
El Bcheraoui C, Memish ZA, Tuffaha M, Daoud F, Robinson M, Jaber S, et al
. Hypercholesterolemia and its associated risk factors-Kingdom of Saudi Arabia, 2013: A National Survey. Ann Epidemiol 2014;2:564-679. [Doi: 10.1016/j.annepidem. 2014.08.001].
Reiner Ž. Statins in the primary prevention of cardiovascular disease. Nat Rev Cardiol 2013;10:453-64.
National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421.
Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr., Clark LT, Hunninghake DB, et al.
Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004;110:227-39.
Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ 1994;308:367-72.
Law MR, Wald NJ. An ecological study of serum cholesterol and ischaemic heart disease between 1950 and 1990. Eur J Clin Nutr 1994;48:305-25.
Law MR, Wald NJ, Rudnicka AR. Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: Systematic review and meta-analysis. BMJ 2003;326:1423.
Arafah M, Al-Hinai AT, Al Mahmeed W, Al-Rasadi K, Al Tamimi O, Al Herz S, et al.
Centralized pan-Middle East Survey on the undertreatment of hypercholesterolemia: Results from the CEPHEUS study in Arabian Gulf countries. Angiology 2014;65:919-26.
McNamara DJ, Howell WH. Epidemiologic data linking diet to hyperlipidemia and arteriosclerosis. Semin Liver Dis 1992;12:347-55.
Memish ZA, El Bcheraoui C, Tuffaha M, Robinson M, Daoud F, Jaber S, et al.
Obesity and associated factors – Kingdom of Saudi Arabia, 2013. Prev Chronic Dis 2014;11:E174.
al-Nuaim AR, Mirdad S, al-Rubeaan K, al-Mazrou Y, al-Attas O, al-Daghari N, et al.
Population-based epidemiological study on characteristics of risk factors of hypercholesterolemia in Saudi Arabia. Int J Cardiol 1997;62:47-54.
Mackay DF, Gray L, Pell JP. Impact of smoking and smoking cessation on overweight and obesity: Scotland-wide, cross-sectional study on 40,036 participants. BMC Public Health 2013;13:348.
Mahmood D, Jahan K, Habibullah K. Primary prevention with statins in cardiovascular diseases: A Saudi Arabian perspective. J Saudi Heart Assoc 2015;27:179-91.
Bates TR, Connaughton VM, Watts GF. Non-adherence to statin therapy: A major challenge for preventive cardiology. Expert Opin Pharmacother 2009;10:2973-85.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]