|Year : 2022 | Volume
| Issue : 1 | Page : 13-21
Dyslipidaemia in Sri Lanka
Anne Thushara Matthias1, Ruvan Ekanayake2, Carukshi Arambepola3
1 Department of Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka
2 Department of Cardiology, Nawaloka Hospital, Colombo, Sri Lanka
3 Department of Community Medicine, University of Colombo, Colombo, Sri Lanka
|Date of Submission||23-Feb-2022|
|Date of Decision||16-Mar-2022|
|Date of Acceptance||25-Feb-2022|
|Date of Web Publication||31-Mar-2022|
Dr. Anne Thushara Matthias
Department of Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda
Source of Support: None, Conflict of Interest: None
Cardiovascular diseases (CVDs) are the leading cause of mortality in South Asia. Although well-recognized as a major risk factor, dyslipidemia in such populations is not well-reviewed. To review the trends in dyslipidemia, phenotypes, underlying causes, treatment modalities, and management gaps in Sri Lanka. A narrative review was undertaken on published literature on dyslipidemia in Sri Lanka from 2000 to 2020, extracted using PubMed, Google Scholar, and locally published literature. Out of the 33 documents reviewed, only a limited number was available on large-scale population-based studies. High prevalence of metabolic syndrome along with moderately high low-density lipoprotein-cholesterol, low high-density lipoprotein-cholesterol, high triglycerides, and high ApoB and Lp(a) concentrations was seen. Familial hypercholesterolemia was an understudied area with a need for a national screening program. With dyslipidemia guidelines limited to the management of special disease groups, there is a chasm between guidelines and practice at present in Sri Lanka. Unlike in primary prevention, prescribing high-dose statins in secondary prevention of CVD has been satisfactory. Treatment gaps are identified, with room for improvements in lipid screening and achieving lipid goals. Considering the substantial burden identified, education of physicians, optimizing lipid testing, and aggressive treatment of lipids are key initiatives toward optimizing management of dyslipidemia.
Keywords: Cardiovascular disease, cholesterol, coronary artery disease, dyslipidemia, lipid, South Asia, Sri Lanka
|How to cite this article:|
Matthias AT, Ekanayake R, Arambepola C. Dyslipidaemia in Sri Lanka. Int J Non-Commun Dis 2022;7:13-21
| Introduction|| |
Cardiovascular disease (CVD) is the leading cause of mortality worldwide. This tendency is much higher in South Asia, which comprises Sri Lanka, India, Pakistan, Bangladesh, and Nepal. More importantly, South Asia signifies premature death from CVD below 65 years of age compared to CVD and other noncommunicable diseases (NCD) in developed countries. Other characteristic features of CVD in South Asia have been the premature onset of disease (<40 years) as well as the severe disease course that it follows.,,, According to the findings of an international case–control analysis of risk factors for a first myocardial infarction (MI) among over 2000 cases and controls of Asian origin (INTERHEART), South Asians were the second-highest ethnic group to have young MI. Their median age at first acute MI was reported as 53 years compared to 63 years in Western Europe.
The underlying causes of CVD in South Asia have predominantly been the well-known conventional risk factors, namely hypertension, dyslipidemia, type 2 diabetes mellitus (DM), abdominal obesity, metabolic syndrome (MetS), and tobacco use. Of these, dyslipidemia appears to be the strongest contributor for MI in South Asia, giving a population attributable risk of 49.2%. It is also highlighted that the odds of getting an MI due to dyslipidemia (ApoB/ApoA1 ratio) would be 3.81 among South Asians
Sri Lanka is a middle-income country in South Asia with a population of over 20 million. It has received many accolades for achieving impressive health indicators despite a low gross domestic product. Of these indicators, the life expectancy at birth of 72 years is remarkable, compared to the shorter age span reported from other countries in the region. Several initiatives have been implicated in this success, such as the well-structured public health system in the country that addresses the control of communicable diseases, maternal and child wellbeing and family planning to a large extent; free education and free health services established as social investments by successive governments; and the improvement of economic and social status of people over the years. These initiatives have led to a demographic transition in the last few decades in Sri Lanka resulting in an aging population; as well as rapid urbanization leading to an epidemiological transition toward a progressive increase of CVD in adult populations. In response, the National NCD Policy of Sri Lanka focuses on primary prevention, with more emphasis placed on the control of most crucial CVD risk factors such as dyslipidemia.
Patient management of dyslipidemia presents unique challenges in Sri Lanka. Currently, the principles in use related to management practices are those originally developed for western populations. However, these guidelines are deemed to be less applicable in Sri Lanka, owing to population-specific differences in the genetic predisposition as well as socio-economic factors underlying this burden in Sri Lanka. Alternatively, the local scientific evidence has not been critically reviewed in the local context, with a view for adopting more pragmatic management practices. To bridge this knowledge gap, a narrative review was undertaken to review the evidence available on the phenotypes, prevention, and treatment related to dyslipidemia in Sri Lanka. The review is intended to identify the major strengths and deficiencies to provide the much-needed directives for improving the clinical practices and future research to reduce the burden in Sri Lanka. Being from the leading country with optimal health indicators and infrastructure in the region, the review findings would be applicable to other countries in South Asia.
| Materials and Methods|| |
A narrative review was undertaken to peruse the evidence available from 2000 up to August 2020 in Sri Lanka. The studies done in Sri Lanka on dyslipidemia which qualify for a systematic review (e.g., having rigorous and explicit methodology) are very few in number. Many findings on dyslipidemia are extracted from larger studies conducted on metabolic risk factors in general. In order to identify the gaps in research and forge forward, a scoping review was thought to be more appropriate than a systematic review as it highlights the problems pertaining to the country. As with narrative reviews, this review attempts to provide up-to-date knowledge on specific themes from a theoretical and contextual point of view, rather than providing a critical evaluation of results as in a systematic review.
In performing the review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines were adhered to. The review was based on literature pertaining to Sri Lanka, which was extracted from articles and reports based on local research studies pertaining to dyslipidemia using multiple sources: Full paper articles based on local studies published in scientific journals locally or elsewhere; the abstract presentations of local studies at international conferences (available as e-copies) and in annual academic sessions, scientific workshops, and local conferences held in Sri Lanka (retrieved as hard copies from the proceeding books of conferences organized by professional colleges and health institutes); the national reports based on periodically conducted surveys such as the WHO Country Reports and STEPwise approach to NCD Surveillance (STEPS) Survey Reports of Sri Lanka; and the WHO desk review on CVD and diabetes in Sri Lanka: 2000–2018 based on all relevant research conducted from 2000 to 2017 in Sri Lanka. For online retrieval of data, PubMed and Google Scholar were used. In addition, a bibliographic database that had been recently developed based on the WHO Desk Review was used.
The inclusion criteria of studies considered for the review were those conducted in Sri Lanka (including multi-center studies done in collaboration with other countries) based on primary data collected for a research purpose or secondary data routinely collected on dyslipidemia or related areas such as CVD, ischemic heart disease, DM and MetS in Sri Lanka. The terms/key words used for the search were “dyslipidaemia,” “lipids,” “cholesterol,” “lipo-proteins,” “Sri Lanka” and “South Asia.” The studies conducted on children, adolescents, pregnant women and Sri Lankan migrants, animal studies, case studies and series, studies conducted on Ayurvedic, complementary or traditional treatment used in dyslipidemia, laboratory-based studies as well as studies with <100 sample size were excluded. No registered protocols were considered for this review. Whenever possible, full text articles of the references were perused. Multiple publications of the same study were removed. The validity and clinical relevance of the articles were discussed before considering them for the review. The authors critically analyzed the evidence in narrative form.
| Results|| |
At the initial screening, 45 publications (research articles and reports) were retrieved from the identified sources. After removing duplicates and excluding the ones that did not fulfill the predetermined criteria, a total of 33 publications were scrutinized and selected for the review by two independent reviewers (TM and CA).
The review is presented under subthemes: Prevalence of dyslipidemia including its regional variation, phenotypes, underlying causes, and gaps in clinical management. Wherever relevant, the findings are discussed in relation to regional and outside the regional variations.
Prevalence of dyslipidemia
Only a limited number of population-based epidemiological studies which are nationally representative were available on the prevalence of dyslipidemia in Sri Lanka [Table 1]. The prevalence was shown to vary widely between 20% and 54% owing to differences in the multiple diagnostic criteria used to identify lipid levels According to the largest epidemiological study (n = 4532) done in 2005 as part of the Sri Lanka Diabetes and Cardiovascular (SLDC) Study, 77.4% of the adults were having some form of dyslipidemia, including reduced high-density lipoprotein-cholesterol (HDL-C less than <40 mg/dL) as the most common type (49.6%) followed by raised total cholesterol (TC over 200 mg/dL) (13%). Furthermore, women showed higher mean TC, HDL-C, low-density lipoprotein-cholesterol (LDL-C), and triglyceride values compared to men across all age groups., In comparison, the latest STEPS survey of 2015, which had been conducted in a nationally representative sample of Sri Lankans aged 18–69 years, selected through multistage-cluster sampling method, highlights the prevalence of raised TC (>190 mg/dL or currently on medication) to be 23.7% (19.1% in males; 28.4% in females), which is higher than the values reported in SLDC and STEPS 2011, implying a rise in TC over the years in Sri Lanka. In comparison with other countries in South Asia, the prevalence of raised TC (TC >200 mg/dL) has been reported as 35% in men and 36% in women in India. In contrast, the prevalence of borderline and high cholesterol (≥200 mg/dL) was around 50% according to the NHANES studies, which was much higher than that in India but similar to some studies done in Sri Lanka. A better understanding of the trends in dyslipidemia can be obtained by carrying out periodic surveys such as STEPS with nationwide representation.
Distribution of the lipid phenotypes
In the INTERHEART study, the mean LDL-C levels have been found to be much lower for South Asians compared to other ethnic groups. Furthermore, it is shown that the proportions of cases with acute MI and controls from Asia having normal LDL-C (<100 mg/dL) were 25.5% and 32.3% respectively (prevalence ratio of 0.789), compared with 19.4% and 25.3% in non-Asians (prevalence ratio of 0.767). In keeping with this trend seen in South Asia, the LDL-C levels in Sri Lanka have been moderately high based on the studies done so far. In a study among patients with first event of acute coronary syndrome (ACS) who had not been on lipid-lowering drugs, the mean LDL-C was 109.98 (standard deviation [SD] = 42.78) mg/dL, while the mean LDL-C was 92 (SD = 36) mg/dL in a cohort study of patients awaiting coronary artery bypass grafting following confirmed coronary artery disease (CAD).
Quite importantly, for a given LDL-C level, the risk of coronary heart disease (CHD) is found to be higher among South Asians, highlighting a higher risk of CHD even at lower LDL-C level. It is not clear why South Asians including Sri Lankans confer such high CHD risk for LDL-C, however, there are several possible mechanisms given in literature. It is said the LDL particle burden is higher and that small LDL particles could be more atherogenic. In concurrence, the INTERHEART study confirmed that South Asians have higher apolipoprotein B (ApoB) concentrations compared to other ethnic groups, indicating that South Asians carry a higher number of atherogenic lipoproteins for any given LDL-C level. Unfortunately, no studies have been done in the county to analyze the LDL particle size or burden.
ApoA and ApoB
There are only a few studies done in Sri Lanka investigating ApoB and ApoA1. According to a study among 995 diabetic patients in Sri Lanka, the mean ApoB was 1.23; ApoA was 1.61 g/l; and ApoB/ApoA1 was 1.61. In a case–control study, CAD patients (cases) revealed a mean ApoA1 of 110.6 (SD = 20.8) and mean ApoB of 95.2 mg/dl (SD = 25.3), both of which were higher compared to the age- and sex-matched healthy volunteers (controls). In comparison with other countries, the limited Sri Lankan studies have shown that mean ApoB concentrations are much higher when compared to INTERHEART, which showed an overall median ApoB concentration of 0.93 g/L in cases and 0.88 g/L in controls and when compared to a study done in India where the mean ApoB serum concentration was 0.78 g/L. The exact reason for this is not known and further studies into the genetics are warranted.
Epidemiologic studies in the world have identified Lp (a) as a risk factor for atherosclerosis, in which Lp (a) concentration of <50 mg/dl has been suggested as a desirable level as a function of global cardiovascular risk. Similarly, Lp (a) concentration of 25 mg/dL has been suggested as the cut-off for reflecting the risk of CHD based on a South Indian study. The estimation of Lp (a) levels is strongly recommended for atherosclerotic cardiovascular disease (ASCVD) risk stratification in Sri Lankan subjects, particularly in those who have a family history or premature CAD. In this regard, a cut-off value of 17.3 mg/dL has been put forward as a risk factor for subjects with family history of premature heart disease. Consequently, subjects with a positive family history of CAD with high serum Lp (a) level (≥17.3 mg/dL) have shown a higher risk for the development of CAD. Since the available studies give a wide range of cut-off values (17.3–50 mg/dL), the exact cut-off value of Lp(a) associated with ASCVD risk is yet to be determined in Sri Lanka.
Triglyceride and high-density lipoprotein-cholesterol
In particular, the South Asians are known to have higher hypertriglyceridemia than Caucasians. According to a recent systematic review, the weighted mean prevalence of hypertriglyceridemia was 37.2% in South Asia. A similar trend is observed on TG in Sri Lanka as well. This atherogenic dyslipidemia is further shown to associate with DM, MetS, and CHD. Although the exact reason is not known, this trend is said to be associated with high carbohydrate diets in South Asia. As evidence, studies done in Sri Lanka on dietary diversity have revealed that Sri Lankans consume an excess amount of starchy food.
Family history and familial hypercholesterolemia as underlying causes of dyslipidemia
In Sri Lanka, a significant proportion (72%) is noted with family history among those with CAD and hypercholesterolemia. On the other hand, familial hypercholesterolemia (FH) is an inherited disorder, which is characterized by an increase in the concentration of LDL-C in plasma. Sri Lanka provides evidence in relation to patients with FH; their average TC level has been reported as 356.8 mg/dL (SD = 66.4) in one study and 366.28 mg/dL (SD = 60.47) in another. The corresponding LDL-C levels have been 250.3 mg/dL (SD = 67.7) and 259.8 mg/dL (SD = 66.98). In comparison, mean TC in the Asian-Indian population has been in the range of 243.62–301.63 mg/dL., which is much lower than that reported for Sri Lanka.
FH predisposes a patient to CHD. Based on the studies done on FH in Sri Lanka, two important findings have been elicited pertaining to Sri Lanka., The first is the relatively low frequency of peripheral stigmata of hypercholesterolemia such as tendon xanthomas or corneal arcus. The second finding is the low frequency of mutations such as LDL receptors, which is likely to be due to polygenic inheritance of FH. The relative paucity of tendon xanthoma among patients with FH has been reported in other studies done in South Asia., The exact reason for this is not known. It could be due to an environment-related cause. There are no studies done on the prevalence of FH in Sri Lanka.
Treatment of dyslipidemia
Lifestyle modifications play a pivotal role in combating dyslipidemia. Cessation of smoking, moderate reduction of alcohol consumption, dietary modification, and physical exercise are some of the components of lifestyle modifications.
From a management perspective, only a few studies have evaluated the effect of exercise on lipids in Sri Lanka. A study done to compare the effects of military training on lipids showed a significant reduction in mean TG as well as LDL-C in all groups that had military training compared to its control group who did not receive any military training. In comparison, a descriptive study done at a single hospital in 120 patients showed that combining diet and exercise reduced the cholesterol level more than that with either diet or exercise alone in 90 days.
In order to promote physical activity, there have been several initiatives taken by political leaders and policymakers in Sri Lanka. As sustainable interventions, substantial modifications have been advocated with regard to the built environment. A series of walking paths and recreational and play areas have been constructed in both urban and suburban areas. School curricula have been revised to promote physical health, while the concept of health-promoting school concept has been established to promote active lifestyles in school children as well as to train them as change agents at home and surrounding communities.
The Sri Lankan Government established “Healthy Lifestyle Centers” in 2011 to provide guidance on healthy lifestyles, screening for CHD risk factors and 10-year CVD risk prediction, and follow-up for individuals between 35 and 65 years. However, only nonfasting random cholesterol testing is performed to screen for dyslipidemia. This is a limitation as the total lipid profile is not done. If lipid profile is not done, elevated TG, LDL-C, low HDL-C will not be detected. These are common lipid abnormalities seen in Sri Lanka.
In 2020, the government introduced screening of healthcare workers for NCDs, in which lipid screening has been made mandatory for claiming for increments. In order to improve the dietary risk factors of NCDs, postgraduate training courses in clinical nutrition have been established to train consultant clinical nutritionists. Their services including that of medical officers in nutrition are offered at state sector hospitals.
Pharmacological therapy and side effects of statins
Several studies looking at the pharmacokinetics and pharmacogenetics of statins in Asian Indians have revealed higher peak plasma concentrations in them compared with Whites. However, whether this relates to a risk of high incidence of statin-induced side effects is not known. There are no laboratory studies done in Sri Lanka on the pharmacokinetics and dynamics of statins.
There is evidence from Sri Lanka on the common side effects of statins based on clinic-based studies. In a study among 375 patients receiving atorvastatin in outpatient clinics of a tertiary-care hospital (5–40 mg; duration: Mean 64.2 months), statin-related muscle disease (SRMD) and myositis were 14.7% (55/375) and 2.1% (8/375), respectively. This is compatible with literature on SRMD as the most common side effect of statins.
In Sri Lanka, many physicians are reluctant to use high-dose statins such as Atorvastatin 80 mg due to concerns regarding increased statin-related side effects and therefore use Atorvastatin 40 mg. In contrast, the few studies done in Sri Lanka however do not indicate any strong relationships between statin dose and side effects. For example, the previously cited clinic-based study showed no association between SRMD and age, gender, atorvastatin dose, treatment duration, or co-medications. Nevertheless, further studies especially randomized controlled trials are needed to evaluate in more depth whether Sri Lankans are sensitive to and whether prone to develop side effects due to higher doses of statins such as the effects of Atorvastatin 80 mg.
Monoclonal antibodies against PCSK9 produce substantial and sustained reductions in LDL-C and other atherogenic lipoproteins. There is no evidence in Sri Lankans for the use of nonstatin therapy such as PCSK9. ODESSY has been one of the main multicenter, randomized, double-blinded, placebo-controlled trials to assess the effectiveness of PCSK9 and this study had 314 participants from Sri Lanka and revealed that alirocumab reduced major adverse cardiovascular events by 24% (absolute risk reduction [ARR] of 3.4%) and all-cause death by 29% (ARR of 1.7%) compared with placebo.
Gaps in the management of dyslipidemia and gaps to be bridged
Based on this review, there are several gaps observed in the current management practices of dyslipidemia in Sri Lanka.
Firstly, there are no guidelines available at present for Sri Lanka on dyslipidemia, other than what is covered in the guidelines specified for management of DM and ST-elevation myocardial infarction, thus limited to aspects of lipid management in special groups of patients. Therefore, the clinical management of dyslipidemia in Sri Lanka is largely based on guidelines developed for other countries. There is a recent guideline from India in 2016, which highlights important management recommendations that can be applied to Sri Lanka. However, considering the regional as well as within the region differences related to dyslipidemia highlighted in this review, it is time to develop a separate guideline or at least an expert consensus or position statement from the local experts. At present, a guideline committee is in the process of preparing dyslipidemia guidelines applicable to Sri Lanka under the patronage of the Ceylon College of Physicians and NCD Unit of the Ministry of Health. This guideline will be unique to Sri Lanka as it will address matters specifically concerning Sri Lankans, such as having an unusually high prevalence of dyslipidemia comprising low HDL-C, high TG, moderately elevated LDL-C and high Lp(a); cultural beliefs, socio-economic conditions, diet, and other factors.
Second, clinical inertia in prescribing statins to those eligible is well observed in Sri Lanka. In a study which identified 270 statin benefit patients, only 72 (26.6%) were on the recommended dose of statin therapy while 70 (25.9%) were not treated with any statin at all.
As at present, there are no major concerns about increased statin intolerance in Sri Lanka when using moderate to high dose statins such as Atorvastatin 40 mg. Based on this evidence, it is rational for clinicians to use the maximum tolerated dose of statin, and for all patients after ACS to receive high dose statins unless there are contraindications. In concurrence, the present practice of prescribing high dose statins to those after ACS for secondary prevention seems to be commendable in Sri Lanka, as evident in an audit carried out in patients with 2116 ACS patients, of whom 1928 (91.1%) received statin on discharge, in comparison to 97.4% reported in a study (MINAP) from the UK. According to another unpublished audit carried out at a tertiary care center in Colombo District, the adherence to high dose statins after ACS has been over 97% (personal communication).
Third, a significant proportion of patients with dyslipidemia, do not seem to achieve the lipid goals pertaining to their risk category as per the guidelines. As per this review, there appears to be room for improvement in achieving recommended therapeutic targets for patients with high risk for CVD in Sri Lanka. In a study done in Sri Lanka on 101 patients, the LDL-C targets recommended by ESC/EAS could be achieved only by 12.9%. Furthermore, among the 80.2% of patients in the very high CVD risk category, the LDL goal attainment was as low as 7.4%, while it was 37.5% in the high CVD risk category consisting of 15.8% of the sample. These highlight failure to achieve targets being more common in high-risk categories. The NHANES which examined 10,367 patients with DM revealed LDL <100 mg/dl in 43.8%. For optimal management of LDL levels and to reach the guideline-recommended targets, frequent lipid testing once statins are initiated is warranted.
Fourth, while many physicians are aware of the need to treat patients aggressively to achieve recommended LDL-C goals, they ignore the importance of optimizing other lipid therapeutic goals like the non-HDL-C and ApoB. This could be due to the lack of familiarity with international guidelines recommendation for these target goals. Educational programs could help in this regard to educate physicians about present recommendations in the guidelines.
Fifth, laboratory testing of lipids in state sector is not adequate. Out of 101 patients, serum TC levels were not checked in any of the patients because of nonavailability of the test. Laboratory strengthening needs to be done to carry out screening and regular lipid profiles in the state sector at all levels of hospitals to optimize lipid management, as per currently practiced in some countries in South Asia. This is vital as if aggressive lipid-lowering is to be done, regular lipid profiling should be available to assess the level of LDL and other lipid parameters to monitor the lipid control. Frequent checking of lipid parameters with the aim of introducing nonstatin therapy in patients whose LDL does not reduce in accordance with the guidelines or for those who have statin intolerance needs to be done in routine clinical practice. In order to improve aggressive lipid management with the aim of achieving lipid targets, educating the physicians through respective professional colleges must be initiated. These should be done at periodic intervals for higher success rates.
Finally, as with any NCD, patient awareness and education about dyslipidemia, its associations, and management are crucial for its successful management. According to a study done on urban-dwelling patients attending the medical clinic with MetS, the patient awareness on a healthy diet to reduce CVD risk was not adequate. In another study done on patients with statin in Sri Lanka, 45% were unaware that they were on treatment with statins. Therefore, an approach to educate patients about lifestyle modifications to reduce dyslipidemia which is individualized and culturally relevant is needed to combat dyslipidemia. Patient education should be strengthened through educational programs.
Areas for future research
Asian dyslipidemia is a unique phenotype. This uniqueness opens a Pandora of opportunities for research. Based on the review, a few areas for future research in dyslipidemia have been identified. There are no large prospective studies in Sri Lanka that have determined the association of various cholesterol fractions with CAD outcomes. FH is also not studied in detail and there is a need for a registry for early identification and optimal management of this patient cohort. At present, there are no studies done on the genetics of dyslipidemia in Sri Lanka. Such studies can identify unique genetic mutations associated with the Sri Lankan dyslipidemia. Furthermore, clinical trials to identify the effects of high doses of statins need to be carried out in Sri Lankan populations, while further studies are needed on nonstatin therapy such as Ezetimibe and PCSK9 inhibitors in Sri Lanka.
| Conclusions|| |
Sri Lankan dyslipidemia is uniquely different from that evidence from studies conducted in western populations. It is much in line with dyslipidemia seen in other South Asian countries, however there are differences noted in relation to higher prevalence of MetS and higher apo B concentrations. The review suggests that more aggressive management of dyslipidemia is crucial for control of CVD in the country. In this regard, more evidence is required on under-studied areas, such as the profile of dyslipidemia and strategies for achieving lipid goals in patients. The areas for future research include efficacy and the profile of side effects of statins, FH and outcomes of lipid management.
Ethical approval statement
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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