journal of july 2016 • vol. 8 • no. 5 the society of

Journal of THE SOCIETY OF PHYSICIANS OF HONG KONG

www.soPHYSICIANShk.orgVisit the web site for our monthly CME programmes for doctors

JULY 2016 • VOL. 8 • NO. 5

ISSN 2072-4209

CONTENTS

53 Message from the President Pictorial Medical History (14) Dr Lam Tat Chung, Paul ( )

54 Overview of IgG4-related Disease: A Novel Entity Dr Chen Yi Tin ( )

58 Unmet Patient Needs: Novel Mechanisms of GERD and Implications on Treatment

Professor Wu Che Yuen, Justin ( )

61 The Important Role of Diet in the Management of Hypercholesterolemia and Prevention of Coronary Heart Disease

Professor Brian Tomlinson ( ) Ms Lam See Way, Sylvia ( ) Ms Lau Wai Yan, Vivian ( )

JUL 2016 Journal of The Society of Physicians of Hong Kong | 53

Pictorial Medical History (14)Dr Lam Tat Chung, Paul ( )FRCP, FRCPsych, FHKAM (Medicine), FHKAM (Psychiatry)Specialist in Psychiatry (Private Practice)Honorary Clinical Assistant Professor, The University of Hong Kong

This Sanctuary is a remarkable testament to the healing cults of the ancient world, and witness to the emergence of scientific medicine. The site is an eminent example of a Hellenic architectural ensemble of the 4th Century BCE. The form of its buildings has exerted great influence on the evolu-tion of Hellenistic and Roman architecture. Today it is a World Heritage Site with over 250,000 visitors annually.

Message from the President

Midyear is the appropriate time to review what we have done in the first half of the year. Earlier this year we published four issues of the Journal, on topics in precision medicine, rheumatology, respiratory

medicine , gastroenterology, cancer and infectious disease. I am most grateful to the authors who dedicated time to work on the Journal and keep our readers up-to-date with very useful information.

For the CME activities, we have been active and produced many exciting programmes. We had a conference on precision medicine, with many speakers from the USA. We continued with our Sunday Symposia and other meetings. Again my heartfelt thanks to all the hard-working doctors who have sacrificed their time and efforts to work on these successful events.

Midyear is also a time to get away from the office for some fun and relax-ation. In July I attended the International College of Neuropsychopharmacology Conference (CINP) in Seoul. I managed to benefit greatly from the lectures and meeting with old and new friends.

Asclepieion at Epidaurus

54 | Journal of The Society of Physicians of Hong Kong JUL 2016

Introduction

Immunoglobulin G4-related disease (IgG4-RD) is a rare fibro-inflammatory disorder of unknown origin, with a

systemic nature which has only recently been recognized. Type 1 autoimmune pancreatitis is the most common mani-festation of IgG4-RD; however, IgG4-RD can affect any organ including salivary glands, orbits, retroperitoneum and many others. The disease is of inter-est to internal medicine physicians and other specialties such as ear, nose & throat, dermatology, ophthalmology, and neurology. Typically lymphoplasmacellu-lar inflammation, storiform fibrosis, and obliterative phlebitis are found in biop-sies of IgG4-RD patients and the tissue- invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. Con-sequently, diagnostic criteria for IgG4-RD have been recently proposed.

This review summarizes current

knowledge on the clinical manifesta-tions, pathophysiology and treatment of IgG4-RD.

IgG4-related diseaseWhile different names for this syndrome have been used over the past 10 years, the term IgG4-related disease has recently evolved as the most appropriate.1

Consequently, the organ manifestations of IgG4-RD were renamed (Table 1).

Clinical manifestationsIgG4-RD can involve one or multiple organs. Patients often present with sub-acute development of a mass in the affected organ (eg, an orbital pseudo-tumor, a renal mass resembling renal cell

Overview of IgG4-related Disease: A Novel Entity

Table 1. Nomenclature for manifestations of IgG4-RD in different organ systems [adapted from Stone JH et al.1]Pancreas IgG4-related pancreatitis (type 1 autoimmune pancreatitis)Bile ducts, gallbladder, and liver IgG4-related sclerosing cholangitis

IgG4-related cholecystitisIgG4-related hepatopathy

Thyroid gland IgG4-related thyroid diseaseSalivary and lacrimal glands IgG4-related sialadenitis

IgG4-related parotitisIgG4-related submandibular gland diseaseIgG4-related dacryoadenitis

Orbits IgG4-related ophthalmic diseaseIgG4-related orbital inflammatory pseudotumorIgG4-related pan-orbital inflammationIgG4-related orbital myositis

Retroperitoneal fibrosis, arteries IgG4-related retroperitoneal fibrosisIgG4-related aortitis/periaortitisIgG4-related periarteritis

Intrapulmonary, mediastinal and pleural involvement

IgG4-related lung diseaseIgG4-related mediastinitisIgG4-related pleuritis

Lymph nodes IgG4-related lymphadenopathyKidney IgG4-related kidney disease

Tubulointerstitial nephritis secondary to IgG4-related diseaseMembranous glomerulonephritis secondary to IgG4-related diseaseIgG4-related renal pyelitis

Miscellaneous IgG4-related perineural diseaseIgG4-related pachymeningitisIgG4-related hypophysitisIgG4-related mesenteritisIgG4-related mastitisIgG4-related prostatitisIgG4-related epididymo-orchitisIgG4-related paratesticular pseudotumorIgG4-related skin diseaseIgG4-related pericarditis


carcinoma, nodular lesions in the lung) or diffuse enlargement of an organ (eg, the pancreas). Multiple organs are affected in 60–90% of patients with IgG4-RD.

Lymphadenopathy is common among IgG4-RD patients, and symp-toms of asthma or allergy are present in approximately 40% of patients. Patients often feel well at the time of diagnosis and are generally afebrile. However, patients with multi-organ disease often lose substantial amounts of weight over the months before being correctly diag-nosed. Clinicians should also be alert to the possibility that IgG4-RD can mimic autoimmune rheumatic diseases such as systemic lupus erythematosus, Sjögren’s syndrome, or granulomatosis with poly-angiitis. IgG4-RD is often recognized incidentally due to radiologic findings or histopathologic examination of a tissue specimen.

Previously IgG4-RD was viewed as uncommon, but manifestations of this disease are now increasingly recognized in nearly every organ system. Many of the initial observations regarding this condition were made in patients with autoimmune pancreatitis (AIP), which often presents as a pancreatic mass or as painless obstructive jaundice, and can be mistaken for pancreatic cancer. Additional reports have focused on patients with lacrimal and salivary gland involvement, formerly termed Mikulicz’s disease, which was once thought to be a subset of Sjögren’s syndrome. Such patients may present with prominent parotid or submandibular gland enlargement.

Diagnosis and pathologyIgG4-RD can affect any organ or tissue, thus the clinical picture is highly het-erogeneous. While some patients may present with a single site involved, oth-ers may have multiple organs affected by IgG4-RD. These may arise synchro-nously or metachronously. The disease may manifest as a tumefactive lesion or a rather diffuse infiltrative process, further contributing to a diverse clinical picture.

In addition, some organs show a distinct involvement, for example, lymphadenop-athy, periaortitis, or a secondary form of membranous glomerulonephritis.2-4

Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be highly elevated, but can be normal despite active disease. Anti-nuclear antibodies, anti-SS-A and anti-SS-B are not present in the majority of IgG4-RD patients, while low complement levels (C3 and C4) are not uncommon. Polyclonal hypergamma-globulinaemia is often found in IgG4-RD and increased serum IgE levels and aller-gic diseases are present in about one third of patients. IgG subclass analyses reveal highly elevated serum IgG4 levels in many but not all patients. It should be empha-sized that IgG4 levels can be misleading when they are used as a sole criterion for diagnosis (or exclusion) of IgG4-RD. A number of other diseases, such as can-cer, infection and autoimmune diseases, including vasculitis, are associated with increased IgG4 levels, and conversely, many IgG4-RD patients may have normal IgG4 levels. Thus, the sensitivity of IgG4 in IgG4-RD was found to be 90% and the specificity 60% in one study,5 and in another study the positive predictive value of an elevated serum IgG4 for IgG4-RD was found to be as poor as 10%.6

While the location of disease manifestation may vary, the histological pattern shares particular features: (i) stori-form fibrosis (resembling the spokes of a cartwheel), (ii) a dense lymphoplasmatic infiltrate with an increased number of IgG4+ plasma cells (at least > 10/high power field (HPF) – depending on the particular organ) and/or an increased IgG4/IgG ratio (usually >40%) and (iii) an obliterative phlebitis. The presence of neutrophils, granulomas, neutrophilic microabscesses, and necrotizing vasculitis indicates that the disease is not IgG4-RD.

EpidemiologyThere are few studies reporting on the epidemiology of IgG4-RD, with most

coming from the Asia-Pacific region. A cross-sectional study in 2009 estimated that approximately 8000 individuals in Japan were suffering from IgG4-RD, thus accounting for a prevalence of approxi-mately 60 affected individuals per mil-lion inhabitants. There are no data on the prevalence of IgG4-RD in Europe or glob-ally, but IgG4-RD is thought to be rarer outside of Asia. IgG4-RD usually affects middle-aged individuals and, for some organ manifestations such as type 1 AIP, a male predominance is evident.

TreatmentOverall, there is no evidence for

treatment options from randomized con-trolled trials. Clinical experience has dem-onstrated that most IgG4-RD patients respond favourably to glucocorticoid (GC) treatment. While it appears that sponta-neous remissions do occur, the use of GC induces remission in most patients, often earlier than would be feasible with-out treatment. However, relapse is fre-quently seen after GCs are tapered or discontinued; relapses may be confined to the originally affected organs but can also occur in other organs. They may be preceded or accompanied by an increase in IgG4 levels.

Whether treatment in patients with IgG4-RD should be initiated depends on the localization and extent of disease manifestation. In some patients with minor involvement (eg, asymptomatic and incidental IgG4-related lymphade-nopathy or small, indolent nodular lesions in IgG4-related lung disease), immedi-ate treatment may not be indicated and follow-up may be more appropriate. In other cases with organ dysfunction or pseudotumours (eg, renal involvement, pancreatitis with bile duct obstruction and jaundice, lacrimal gland swelling, pachy-meningitis), rapid introduction of therapy is necessary to avoid loss of organ func-tion. Thus, treatment decisions have to be individualized.

In general, most experts would start with a dosage of 40 mg prednisolone


or 0.6 mg/kg of body weight per day and taper the dose over several months, with the first dose reduction after 2–4 weeks.7-9 Treatment response is usually seen within 2–4 weeks; how-ever, some disadvantages of the use of GCs are adverse effects as well as the need for maintenance therapy. Hence a number of drugs including azathioprine, mycophenolate mofetil or methotrexate have been used as GC-sparing agents. In addition, more intensive therapies such as cyclophosphamide, fludarabine and bortezomib have been reported to be of benefit in IgG4-RD patients.

A promising treatment strategy in GC-dependent or refractory patients is rituximab (RTX).10,11 RTX has been used in a case series of 10 refractory IgG4-RD patients but the duration of treatment effect was not established. One major interesting finding was that RTX specifi-cally reduced IgG4 levels, while the other IgG subclasses remained stable.

SummaryIgG4-related disease is a condition that mimics many malignant, infectious, and inflammatory disorders. This multi-organ immune-mediated condition links many disorders previously regarded as iso-lated, single-organ diseases without any known underlying systemic condition. It was recognised as a unified entity only 10 years ago and histopathology is the key to diagnosis. The three central pathol-ogy features of IgG4-related disease are lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis. The extent of fibrosis is an important deter-minant of responsiveness to immunosup-pressive therapies. IgG4-related disease generally responds to GCs in its inflam-matory stage, but recurrent or refractory cases are common. Important mechanis-tic insights have been derived from stud-ies of patients treated by B-cell depletion (RTX). Greater awareness of this disease is needed to ensure earlier diagnosis,

which can prevent severe organ damage, disabling tissue fibrosis, and even death. Identification of specific antigens and T-cell clones that drive the disease will be the first step to elucidating the pathogen-esis of IgG4-related disease.

References1. Stone JH, et al. Recommendations for the nomenclature of IgG4-related

disease and its individual organ system manifestations. Arthritis Rheum. 2012, 64: 3061-3067.

2. Grimm KE, et al. Histopathological findings in 29 lymph node biopsies with increased IgG4 plasma cells. Mod Pathol. 2012, 25: 480-489.

3. Zen Y, et al. Retroperitoneal and aortic manifestations of immunoglobulin G4-related disease. Semin Diagn Pathol. 2012, 29: 212-218.

4. Alexander MP, et al. Membranous glomerulonephritis is a manifestation of IgG4-related disease. Kidney Int. 2013, 83: 455-462.

5. Carruthers MN, et al. The diagnostic utility of serum IgG4 concentrations in IgG4-related disease. Ann Rheum Dis. 2015; 74: 14-18.

6. Ngwa TN, et al. Serum Immunoglobulin G4 Level Is a Poor Predictor of Immunoglobulin G4-Related Disease. Pancreas. 2014, 43: 704-707

7. Stone JH: IgG4-related disease: nomenclature, clinical features, and treatment. Semin Diagn Pathol. 2012, 29: 177-190.

8. Kamisawa T, Takeuchi T: Treatment of autoimmune pancreatitis with the anecdotes of the first report. Int J Rheumatol. 2012, 2012: 597643

9. Ghazale A, Chari ST: Optimising corticosteroid treatment for autoimmune pancreatitis. Gut. 2007, 56: 1650-1652.

10. Topazian M, Witzig TE, Smyrk TC, Pulido JS, Levy MJ, Kamath PS, Chari ST: Rituximab therapy for refractory biliary strictures in immunoglobulin G4-associated cholangitis. Clin Gastroenterol Hepatol. 2008, 6: 364-366

11. Khosroshahi A, Bloch DB, Deshpande V, Stone JH: Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic disease. Arthritis Rheum. 2010, 62: 1755-1762.

THE SOCIETY OF PHYSICIANS OF HONG KONGCOMING EVENTS

Sep 11, 2016 Sunday Symposium Langham Hotel

Sep 25, 2016 Sunday Symposium Langham Hotel

Oct 16, 2016 Sunday Symposium Langham Hotel

Oct 26, 2016 (Wed) Lunch CME HKMA in Central

Nov 13, 2016 Anniversary Scientific Meeting Langham Hotel

Nov 20, 2016 60th Anniversary Dinner Jockey Club

Dec 18, 2016 Sunday Symposium and Christmas Lunch Langham Hotel

For further details, please visit our website www.SOPHYSICIANSHK.org


BackgroundGastroesophageal reflux disease (GERD) is a chronic disease resulting from the stomach contents regularly flowing back into the oesophagus. The gastric acid present in the reflux leads to symptoms such as heartburn and acid regurgitation, which impairs patient quality of life and reduces productivity.1 In severe cases, acid can accumulate in the oesopha-gus leading to complications such as oesophagitis, stricture and Barrett’s oesophagus.2

Historically, GERD was considered to be primarily a Western disease (preva-lence: 10–20%) and uncommon in Asia (prevalence: 8.9% in Hong Kong and 2.5–7.8% across East Asia).3-5 However, there is evidence to suggest that the prevalence of GERD in Asia is increasing;6 therefore, developing therapeutic strate-gies for maintaining remission amongst

Asian patients will be important for mini-mising GERD-related burden of disease.

Current treatment strategies for GERDConventional therapies for GERD include long-term proton pump inhibitor (PPI) therapy or laparoscopic anti-reflux surgery (LARS). Both therapies demonstrate simi-lar efficacy with one clinical trial report-ing 5-year remission rates of 92% and 85% for patients assigned to PPI therapy (n=192) or LARS (n=180), respectively.7 While surgery significantly reduces reflux, the majority of patients still rely on medical intervention post-surgery, such as PPI therapy, because patients often develop post-operative dysphagia, bloating and flatulence.7

However, despite PPI therapy often being a first line treatment in GERD, PPI therapy has limited efficacy, with up to 45% of patients taking PPIs remaining symptomatic.8,9 Ethnicity may have a role in a patient’s response to PPI ther-apy, with a large multinational prospec-tive trial reporting that Asian patients are significantly less likely to respond to PPI therapy compared with Western patients.10 However, this outcome may have been confounded by relative dis-ease severity as Asian patients typically presented with a more severe disease profile including non-erosive reflux dis-ease (NERD) and severe tissue erosion.10

Furthermore, concern has been raised over the long-term risks associated with PPI therapy. Chronic PPI administra-tion is associated with an increased risk of fractures,11 Clostridium difficile colitis12 and possible drug-drug interactions in patients with a history of an acute coro-nary syndrome prescribed clopidogrel.13 These unmet needs provide the basis for identifying alternative therapeutic

options for patients with GERD that avoids chronic PPI therapy.

The acid pocket: A novel therapeutic target in the treatment of GERDGiven the often inadequate therapeutic response of patients with GERD to PPIs, there is a need to identify novel mecha-nisms involved in the pathophysiology of GERD that could be targets for new therapeutic strategies. For example, there is emerging evidence that an acid pocket forming as a result of the non-homoge-nous distribution of gastric contents dur-ing the post-prandial period contributes to post-prandial acid reflux in patients with GERD.14,15 While most of the distal stom-ach gastric acid is buffered by food, which is facilitated by peristaltic motility, the prox-imal stomach remains relatively immotile during this period, thereby promoting the accumulation of acidic gastric secretions at the gastroesophageal squamocolumnar junction, forming an acid pocket.14

While the acid pocket is a typical phenomenon during the post-prandial period in all individuals, in patients with GERD the acid pocket is longer and can extend through the oesophagogastric junc-tion.16 Similarities in pH have been found between the oesophageal refluxate and the acid pocket, suggesting the acid pocket is likely the source of post-prandial acid reflux in patients with GERD.15 Therefore, the acid pocket represents a unique thera-peutic target for the treatment of GERD.

Alginate as an add-on therapy in non-responsive GERD patientsAlginate-antacid formulations have dem-onstrated target specificity by accumulat-ing at the acid pocket. As alginate-antacid

Unmet Patient Needs: Novel Mechanisms of GERD and Implications on Treatment


formulations contain a polysaccharide polymer, they form a gel upon expo-sure to the low pH environment of the acid pocket.17 By incorporating sodium bicarbonate into the formulation, carbon dioxide is liberated when the gel forms and is trapped in the gel matrix, causing the gel to float above the acid pocket, forming a ‘raft’ (Figure 1).17 This raft subsequently displaces the acid pocket below the diaphragm, providing a physi-cal barrier against regurgitation.18

These alginate-antacid formulations have been demonstrated to be efficacious in reducing oesophageal reflux in patients who have not responded to PPI therapy. In a double-blind, placebo-controlled trial in patients with persistent moderate heartburn, despite PPI therapy, changes in heartburn reflux dyspepsia questionnaire (HRDQ) scores at Day 7 were significantly greater for patients randomly assigned to receive PPI therapy in conjunction with an alginate-antacid formulation (Gaviscon Advance; n=66), versus placebo (n=70).19 Alginate-antacid (Gaviscon Advance) as an add-on therapy significantly reduced the frequency of heartburn, overall reflux and night-time symptoms compared with pla-cebo (Figure 2).19 Additionally, the Gavis-con Advance alginate-antacid formulation was well tolerated with no difference in adverse events being reported between study arms. Collectively, these findings suggest that the Gaviscon Advance algi-nate-antacid formulation is an effective adjunct to PPI therapy for patients with GERD.

ConclusionThe identification of the acid pocket in the proximal stomach as the origin of acid reflux has led to the emergence of novel therapies that selectively target this region. The unique raft-forming mecha-nism of action of alginate-antacid formu-lations has proven efficacy in specifically targeting the acid pocket to reduce the symptoms of GERD and improve patient quality of life. Collectively, these data sug-gest that the Gaviscon Advance alginate-

antacid formulation may be an effective adjunctive therapy for patients who are only partially responsive to PPI therapy, reducing the need for multiple dosing with PPI inhibitors.

References1. Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R. The Montreal

definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006;101:1900–1920.

2. Pisegna J, Holtmann G, Howden CW, et al. Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2004;20:47–56.

3. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005;54:710–717.

4. Wong WM, Lai KC, Lam KF, et al. Prevalence, clinical spectrum and health care utilization of gastro-oesophageal reflux disease in a Chinese population: a population-based study. Aliment Pharmacol Ther 2003;18:595–604.

5. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2014;63:871–880.

6. Ho KY, Cheung TK, Wong BC. Gastroesophageal reflux disease in Asian countries: Disorder of nature or nurture? J Gastroenterol Hepatol 2006;21:1362–1365.

7. Galmiche JP, Hatlebakk J, Attwood S, et al. Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial. JAMA 2011;305:1969–1977.

Alginate

Alginate clot atGE junction andair-meal interface

Oesophagus

Regular antacidat antrum

Oesophagus

Air

Meal

Air

MealAlucol

Sodium bicarbonate + HCl CO2+ H2O + NaCl

Alginic acid + CO2Alginate raft

Sodium alginate + HClAlginic acid + NaCl

Figure 1. Alginate-antacid formulations form a ’raft’ that floats above the acid pocket.17

• Inclusion criteria: Patients ≥18 years with symptomatic GERD, despite daily PPI therapy for at least 4 weeks• Gaviscon Advance (n=66): 10 mL oral suspension containing 1000 mg sodium alginate/200 mg potassium bicarbonate taken 4 times daily after a meal for 7 days• Placebo (n=70): 10 mL oral suspension taken 4 times daily after a meal for 7 daysPrimary endpoint: Change in HRDQ score from baseline for heartburn and regurgitation

0.0

-1.0

-2.0

-3.0

-4.0

-5.0

-6.0

Re�ux†

(p=0.03)

Ch

ang

e fr

om

bas

elin

e in

HR

DQ

re�

ux

sco

re

43% greaterreduction*

Gaviscon Advance alginate-antacid formulation + PPIPlacebo + PPI

Heartburn(p=0.02)

40% greaterreduction*

Regurgitation(p=0.11)

47% greaterreduction

Dyspepsia(p=0.48)

42% greaterreduction

-5.0

-3.5

-2.8

-2.0 -2.2

-1.5 -1.7-1.2

Figure 2. Change from baseline in the self-assessed, daily recall, patient heartburn, reflux, dyspepsia questionnaire (HRDQ) score across domains for patients administered a PPI with or without an alginate-antacid.19

*P<0.05 versus placebo; †sum of score for heartburn and regurgitation; GERD, Gastroesophageal reflux disease; PPI, proton-pump inhibitor

GE, gastroesophageal.

A complete list of references can be downloaded from www.SOPHYSICIANSHK.org


IntroductionCardiovascular diseases (CVD), particu-larly coronary heart disease (CHD), are globally a leading cause of premature mortality. Moreover,1 CHD is the lead-ing cause of disability-adjusted life years (DALYs) worldwide.2 Raised low-density

lipoprotein cholesterol (LDL-C) is a major risk factor for CHD; therefore, the prime focus of prevention and management of CHD should be lowering LDL-C and keep-ing it low throughout life.3,4

In a population survey in Hong Kong in 1995, the average LDL-C level in adults was 3.33 ± 0.83 mmol/L in men and 3.20 ± 0.91 mmol/L in women, with levels increasing with increasing age in both sexes.5 The prevalence of hyperlipi-daemia in the Hong Kong population was only slightly less than that in Caucasian communities with high rates of CHD.5

The prevalence of CHD in Hong Kong has previously been lower than that in the Chinese population in Singapore, prob-ably because of differences in dietary fat intake and LDL-C levels.6 The number of deaths in Hong Kong due to CHD has increased gradually over the last 30 years and the crude death rates in 2014 were 75.2 and 45.6 per 100,000 population for males and females, respectively.7 How-ever, because of the aging population, the overall age-standardized death rate of CHD has shown a decreasing trend since 1990.

The Important Role of Diet in the Management of Hypercholesterolemia and Prevention of Coronary Heart Disease


A healthy diet plays an important role in lowering blood cholesterol and is an effective way of reducing CHD mortality.8 This article reviews the role of a healthy diet in the prevention and management of CHD and other atherosclerotic vascular diseases as well as the key features of a cholesterol-lowering diet.

The role of diet in the management of hypercholesterolaemia and prevention of CVDLowering LDL-C has been shown to be beneficial in reducing cardiovascular events and CVD mortality, irrespective of the method by which the reduction is achieved.9 International guidelines state that dietary modifications and other lifestyle measures should form the basis for CVD prevention.3,4,10

Recent research has shown that prolonged exposure to lower LDL-C levels in early life is associated with a substantially greater reduction in the risk of CHD than treating high LDL-C levels later in life.11 Therefore, lower-ing LDL-C earlier in the disease process through changes towards a healthy diet and lifestyle should be encouraged. A heart-healthy diet has been shown to be effective in reducing CHD mortality8 and can be implemented safely from an early age.4,12

Everybody benefits from heart-healthy dietary changesHealthy lifestyle and dietary changes should form the basis of the manage-ment of hypercholesterolaemia, and medication should be reserved for high-risk patients.3,4

Recent studies have shown that adhering to five simple lifestyle behav-iours – a healthy diet, moderate alcohol intake, no smoking, regular physical activ-ity and maintaining a healthy weight – can prevent more than 80% of coronary events in both men13 and women.14

Table 1. Approximate efficacy of dietary modifications in LDL-cholesterol reduction.

Dietary measure Dose/change in diet Approximate reduction in LDL-cholesterol

Substitution of saturated fats (SFAs) with unsaturated fats, ie, polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs)

Exchange 5% TEI of SFA with PUFA

7%28

Exchange 5% TEI of SFA with MUFA

6%28

Increase in dietary fibre intake from foods rich in soluble fibre

≥3 g/day β-glucan 5–6%29

Addition of plant stanols/sterols 1.5–3.0 g/day 7–12.5%30

Reduction of dietary cholesterol intake <300 mg/day 3%31

LDL, low-density lipoprotein; TEI, total energy intake

Table 2. Summary of dietary recommendations included in guidelines for the prevention of CVD.

Dietary measureHong Kong Centre for Health Protection, 201532

ESC/EAS Guidelines, 201110

International Atherosclerosis Society, 20134

Total fat 15–30% of TEI 25–35% of TEI 20–25% (Pacific Rim countries)

30–35% (Mediterranean countries)

Saturated fat (SFAs) <10% of TEI <7% of TEI <7% of TEI

Monounsaturated fat (MUFA) NA Predominant Replace saturated fat with MUFA and PUFA Polyunsaturated fat (PUFA) NA n-6 PUFA limited

to 10%

Trans fat <1% of TEI <1% of TEI <1% of TEI

Dietary cholesterol <300 mg <300 mg <200 mg

Dietary fibre 25 g 25–40 g Not specified

Soluble fibre Not specified 7–13 g 10–25 g

Plant stanols/sterols NA 1–2 g per day 2 g per day

Sodium 2,000 mg 2,000 mg Limited

Added sugar < 10% of TEI < 10% of TEI Limited

Omega 3 (fatty fish) NA At least 2–3 portions of fish per week are recommended together with regular consumption of other food sources of n-3 PUFAs (nuts, soy, and flaxseed oil)

Consume some fish rich in omega-3 fatty acids

CVD, cardiovascular disease; ESC, European Society of Cardiology; EAS, European Atherosclerosis Society; NA, not applicable; TEI, total energy intake


In a prospective cohort study of over 84,000 healthy women, replac-ing saturated fats with unsaturated fats or whole grain products significantly reduced the risk of CHD.15 Moreover, a Mediterranean diet was shown to reduce the incidence of cardiovascular events by 30% as primary prevention in a high-risk population.16

A healthy diet also reduces coro-nary events as secondary prevention17 and is important in the management of familial hypercholesterolaemia.18,19 Health professionals could substantially reduce CVD recurrence and save lives globally by highlighting the importance of healthy eating.17

Dietary measures recommended for CVD preventionThe most effective and widely- recommended dietary measures for lowering cholesterol are: 1) choosing unsaturated fats instead of saturated fats, 2) increasing the intake of dietary fibre, especially soluble fibre and 3) including foods with added plant stanols or ste-rols.3,4,10 The effect of dietary cholesterol on serum cholesterol levels is relatively small.10 Table 1 presents the approximate efficacies of different dietary measures in reducing serum LDL-C and Table 2 summarizes the key features of a heart-

healthy diet according to guidelines.It is important to help patients

make healthy dietary choices in practice. One example of a healthy dietary pattern is the Dietary Approaches to Stop Hyper-tension (DASH) diet, which emphasizes fruits, vegetables and low-fat dairy products; it also includes whole grains, poultry, fish and nuts but is lower in red meat, sweets and sugar-sweetened beverages. The DASH diet has been shown to be effective in reducing blood pressure20 and blood lipids,21 and obser-vational data suggest that it is associ-ated with a lower risk of CVD.22 Table 3 summarizes the key changes in food choices that may promote cardiovascular health and should be advised for patients.

Foods with added plant stanols, such as yogurt drinks, have been shown to lower blood LDL-C by an average of 10% when consumed daily in recom-mended amounts and as part of daily meals. The cholesterol-lowering effect of plant stanol ester can be measured after 2 to 3 weeks of use and is sustained during continuous use.23

Whereas a healthy diet should be recommended for everyone, including children to adults, the use of foods with added plant stanols is intended for indi-viduals with raised serum cholesterol, especially 1) individuals with high LDL-C at low or intermediate cardiovascular risk

who do not qualify for statin therapy, 2) high- and very high-risk patients, such as patients with diabetes, who fail to reach their LDL-C targets on statins alone, or are statin intolerant and 3) adults and children with familial hyper-cholesterolaemia.23

Dietary changes needed in Hong KongAccording to a dietary survey that was conducted in Hong Kong in 1995 and 1996, the average intake of fat (29% of energy) and saturated fat (8% of energy) followed dietary recommendations.24,25 However, as the frequency of eating out has increased,26 the quantity and quality of fat in the diet today may be less beneficial. The intake of dietary fibre in the Hong Kong population may be low since only one fifth of the population aged 18 to 64 years meets the recommended intake of five portions of fruit and vegetables per day.27 Moreover, almost two thirds of the population consumes less than three servings of grain products per day, and the grains tend to be refined instead of whole grains.26

Thus, the Hong Kong population should be encouraged to increase their consumption of fruit, vegetables and whole grains. Moreover, controlling the intake of saturated fat by limiting fatty

Table 3. Recommended dietary patterns for promoting cardiovascular health.

Increase intake of Exchange Limit intake of

Vegetables

Pulses

Fruits and berries

Nuts and seeds

Fish and seafood

Poultry without skin

Soybean products

Foods with added plant stanols/sterols

Refined cereals

for

Wholegrain cereals Processed and canned meat

Red meat

Offal meats

Deep fried foods, pastries, cakes

Beverages and foods with added sugar (eg, sucrose, fructose, honey, glucose)

Fruit juices

Salt and high sodium condiments

Alcohol

Butter, lard, coconut oil, palm oil, butter-based spreads, solid margarine-based spreads (high trans-fat)

Vegetable oils (eg, canola oil, olive oil), vegetable oil-based fat spreads

High-fat dairy products Low-fat or fat-free dairy products, soy milk


meat, deep fried foods, Chinese pastries,

full fat milk products and sources of hid-

den saturated fats and trans fats, such as

Chinese dim sum, is also recommended.

Consumption of cooking oils with a high

content of n-3 polyunsaturated and/

or monounsaturated fats (eg, canola

oil, olive oil) should also be encouraged

(Table 3).

For patients who need intensified

cholesterol management, foods with

added plant stanols should be consid-

ered in order to enhance the cholesterol-

lowering effect of the diet.

Conclusion A healthy diet should always form the

cornerstone of the management of

hypercholesterolaemia and cardiovascular

risk. Healthcare professionals have an

important role in encouraging their

patients to make healthy cholesterol-

lowering dietary changes. Increasing the

intake of dietary fibre, replacing saturated

fats with unsaturated fats, and adding

foods with added plant stanols into

the diet are the three key measures by

which patients can effectively lower their

cholesterol through their diet.

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