Citation Hong Kong Medical Journal, 2007, v. 13 n. 4, suppl. 4, p

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Title Cost-effectiveness of low-salt diet for lowering blood pressure in the Hong Kong Chinese population Author(s) Cheung, BMY; McGhee, SM; Lau, CP; Ng, P Citation Hong Kong Medical Journal, 2007, v. 13 n. 4, suppl. 4, p. 32-36 Issued Date 2007 URL http://hdl.handle.net/10722/124910 Rights This work is licensed under a Creative Commons Attribution- NonCommercial-NoDerivatives 4.0 International License.; Hong Kong Medical Journal. Copyright Hong Kong Medical Association.

HEALTH SERVICES RESEARCH FUND HEALTH CARE AND PROMOTION FUND Cost-effectiveness of low-salt diet for lowering blood pressure in the Hong Kong Chinese population Key Messages 1. A low-salt diet lowers blood pressure, is cost-effective and well accepted by patients, so hypertensive patients should be encouraged to reduce their salt intake. 2. Most hypertensive patients are likely to need more than one antihypertensive drug in combination with a low-salt diet. 3. For the general population, the strategy should be to maintain an ideal body weight and recommended salt intake. Hong Kong Med J 2007;13(Suppl 4):S32-6 Department of Medicine, University of Hong Kong, Room 405B, 4/F, Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China BMY Cheung, CP Lau Department of Community Medicine, The University of Hong Kong, 5/F William MW Mong Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China SM McGhee Department of Dietetics, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China P Ng HSRF project number: 811028 Principal applicant and corresponding author: Dr BMY Cheung Department of Medicine, The University of Hong Kong, Room 405B, 4/F, Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China Tel: (852) 2855 4768 Fax: (852) 2872 5828 E-mail: mycheung@hkucc.hku.hk Introduction Hypertension affects one in 10 adults in Hong Kong 1 and is a risk factor for coronary heart disease and strokes. One of the environmental factors that may promote the development of hypertension is a high-salt intake. The Intersalt project 2 was a study of over 10 000 subjects from 52 centres in different countries and showed a relationship between sodium and blood pressure levels. In a dietary and nutritional survey of British adults, a difference in sodium intake of 100 mmol was associated with a blood pressure difference of 5 mm Hg/1 mm Hg in men and 7 mm Hg/4 mm Hg in women. 3 Many studies have failed to show a relationship between sodium intake and blood pressure because of regression dilution bias and short study durations. Studies that involved salt restriction for more than 4 weeks showed a blood pressure reduction as predicted. 4-6 In Caucasians, the relationship between blood pressure and sodium intake is still questioned. The food industry prefers to ignore the evidence. Three quarters of dietary sodium in the western diet is hidden in processed food. A substantial reduction in sodium intake would require the purchase of expensive food items or a change in food industry practices. In Chinese, there is a clearer relationship between blood pressure and sodium intake. 2 Moreover, there is a steep rise in blood pressure with age, associated with a high-sodium intake. In Hong Kong, the prevalence of hypertension rises from below 1% in people under 35 years to 27% in men and 36% in women over 65. 1 Dietary salt intake in Hong Kong is high, the mean being 203 mmol Na/day. 1 Local studies show that blood pressure is related to sodium intake. 7 A high-salt intake may be a risk factor for stroke independent of blood pressure. The benefits are much larger if a significant reduction in blood pressure can be achieved. Reducing salt intake by several mm Hg may be sufficient to enable reduction or withdrawal of antihypertensive medications in patients with mild hypertension. Although a lowsalt diet is safe and cheap, its cost-effectiveness needs to be established, as there is demand on dieticians time and a change in spending on food. Our hypothesis was: because blood pressure levels are related to sodium intake, a low-salt diet might be efficacious and cost-effective in patients with borderlineto-mild hypertension. Methods This study was conducted from October 1998 to September 2000. The faculty ethics committee approved the protocol. Relationship between sodium intake and blood pressure in normal adults Adults between the ages of 18 and 75 years inclusive who were not current hospital patients were recruited. They were asked to come to the Queen Mary Hospital, were questioned about their medical and dietary histories and had their height, weight, waist-hip ratio, body fat, dietary patterns, exercise and alcohol habits, blood pressure, 24-hour urinary electrolytes, plasma electrolytes assessed. High-sodium food items regularly consumed by these subjects were identified. 32 Hong Kong Med J Vol 13 No 4 Supplement 4 August 2007

Cost-effectiveness of low-salt diet for lowering blood pressure (a) (b) (c) Female Male Female Male r=0.52, P<0.001 r=0.53, P<0.001 r=0.65, P<0.001 120 160 110 100 160 140 90 80 120 70 140 100 60 120 50 100 80 40 90 10 20 30 40 50 60 70 80 50 60 70 80 90 100 110 120 10 50 60 70 80 Age (years) Waist circumference (cm) 24-Hour urinary sodium (mmol/day) Systolic pressure (mm Hg) Diastolic pressure (mm Hg) 24-Hour ambulatory systolic pressure (mm Hg) Fig 1. Relationship between sodium intake and blood pressure in normal adults Randomised controlled trial of sodium restriction in the treatment of mild essential hypertension A total of 93 patients with mild-to-moderate hypertension (pre-treatment diastolic blood pressure of 90-110 mm Hg) attending the hypertension out-patient clinic were recruited and gave informed consent. All patients underwent a 4- week placebo run-in phase; 74 patients were randomised to conventional treatment (hydrochlorothiazide 25 mg daily or metoprolol 100 mg daily) or a low-sodium (80 mmol/day) diet for 6 months. At baseline, 3 months, and 6 months, 3- day food diaries were completed. The patients were seen by a dietician and completed food frequency questionnaires. The data yielded by these were used in a nutrient analysis (Nutrient Analysis System, Nutritionist IV; N-Squared Computing, First DataBank Division, San Bruno [CA], US). Those allocated to conventional treatment received conventional lifestyle advice from a doctor and a nurse, and were given drugs needed to achieve a target seated diastolic blood pressure of <90 mm Hg. Those allocated to the lowsodium diet received special instructions from a dietician regarding a low-sodium (80 mmol/day) intake. They were then seen at monthly intervals, when their food diaries were reviewed to monitor their dietary intake and compliance, and the dietary advice reinforced. Blood pressure and 24-hour urine sodium measurements were performed at baseline, 3 months, and 6 months. If the blood pressure exceeded 160/90 mm Hg after 3 months of a low-sodium diet, antihypertensive medication was started. Patients on the low-sodium diet were asked to rate the diet and their quality-of-life was assessed by a questionnaire (WHOQOL- BREF [HK]). Cost-effectiveness of salt reduction vs drug therapy Cost-effectiveness ratios (cost per mm Hg fall in diastolic blood pressure) were calculated for the low-salt diet and conventional treatment. The costs included health service costs and patient costs. Health service costs included the dietician s and doctor s time, costs of drugs, and laboratory tests. Patient costs include changes in the cost of food, food supplements, and lifestyle, as well as the costs of extra visits to see the dietician. To test the robustness of the cost difference between diet and drugs, we performed a sensitivity analysis, varying the cost of drugs and food, the dietician s time, and the degree of blood pressure lowering. Results The relationship between sodium intake and blood pressure in normal adults Altogether 190 adults were studied. Of these, 151 were normotensive and 39 were hypertensive. Systolic blood pressure correlated with age (r=0.52, P<0.001) [Fig 1a] and various indices of obesity, including body mass (r=0.24, P=0.001), body mass index (r=0.36, P<0.001), waist-hip ratio (r=0.49, P<0.001), and waist circumference (r=0.44, P<0.001). Diastolic blood pressure correlated with age (r=0.35, P<0.001), sex (r=0.27, P<0.001), and various indices of obesity, including body mass (r=0.39, P<0.001), body mass index (r=0.39, P<0.001), waist-hip ratio (r=0.53, P<0.001), and waist circumference (r=0.53, P<0.001) [Fig 1b]. The 24-hour urinary sodium excretion did not correlate significantly with the systolic and diastolic blood pressures but did correlate with the 24-hour ambulatory systolic blood pressure (r=0.65, P<0.001) in 23 subjects who underwent ambulatory blood pressure monitoring (Fig 1c). Randomised controlled trial of sodium restriction in the treatment of mild essential hypertension Thirty-six patients were randomised to drug treatment (with hydrochlorothiazide 25 mg daily [n=19], metoprolol 100 mg daily [n=15], or perindopril [n=2]) and 38 to a lowsodium diet. Their baseline characteristics (mean±sd) are shown in Table 1. In the low-sodium diet group, there was a significant decrease in sodium intake (54±11 mmol/day), as assessed by the nutrient analysis (Table 2). Sodium intake assessed by the nutrient analysis correlated with 24-hour urinary Hong Kong Med J Vol 13 No 4 Supplement 4 August 2007 33

Cheung et al Table 1. Baseline characteristics of randomised subjects Baseline characteristics Mean±SD Diet group Drug group No. of subjects 38 36 % of male 50 42 Age (years) 45±12 41±9 Weight (kg) 69.5±12.9 67.8±12.6 Body mass index (kg/m 2 ) 26.1±6.7 25.6±6.1 Waist circumference (cm) 89.4±10.9 85.2±11.2 24-h Na + (mmol/day) 194.6±84.7 192.7±73.8 Systolic blood pressure (mm Hg) 142±12 142±11 Diastolic blood pressure (mm Hg) 94±8 96±6 Heart rate (beats per minute) 70±8 72±9 Table 3. Commonly eaten foods that are high in sodium content Food Typical portion (g) Sodium content (mmol) Ham 40 23.1 Dim sum 100 26.7 Marinated spare ribs 80 23.1 Chinese barbecue pork 80 36.9 Instant noodles 100 49.6 Fish balls 60 17.4 Sausages 34 19.1 Fried rice 23.6 Preserved vegetables 40 37.7-140.6 Luncheon meat 28 16.2 Table 2. Sodium intake in the diet and drug groups Sodium intake (mmol/day) Mean±SD Baseline 3 Months 6 Months No. of subjects 74 63 62 Diet group 178.2±12.2 122.9±10.7 * 124.6±10.0 * Drug group 168.3±8.7 158.1±9.5 153.9±9.0 * P<0.05 vs baseline and drug group sodium excretion (r=0.3, P<0.001). Using dietary recall, foods with a high-sodium content were identified (Table 3). In the diet group, there was a significant decrease in body mass and body fat (2.1±0.4%; Table 4). After five visits, 14 patients in the diet group required drug treatment to control their blood pressure. Changes in blood pressure, heart rate, urinary sodium and potassium excretion, body mass, and left ventricular mass index are shown in Table 4. There was a significant decrease in ambulatory systolic and diastolic blood pressure in the drug (16±3 mm Hg and 9±2 mm Hg) and diet group (9±2 mm Hg and 6±1 mm Hg). The decreases in ambulatory blood pressure were significantly larger in the drug group compared to the diet group. In the diet group, the decrease in sodium intake correlated with the decrease in diastolic blood pressure (r=0.44, P=0.02; Fig 2) but not with systolic blood pressure (r=0.35, P=0.1). Cost-effectiveness of salt reduction vs drug therapy The health service costs and the patient costs for diet and drug therapy are listed in Table 5. There were 32 subjects in the diet group and 29 in the drug group with economic data available for analysis. The costs of medications were $30.4±9.3 and $157.7±28.1 in the diet and drug groups, respectively (P<0.001). Health service costs per subject were $764.5±13.9 in the diet group and $736.1±29.5 in the drug group. Total costs per subject were $591.6±163.4 in the diet group and $774.8±75.0 in the drug group. The cost-effectiveness ratios for diet and drug therapy were $103.1±56.7 and $69.6±39.6 per mm Hg decrease in diastolic blood pressure. These were not significantly different. A sensitivity analysis showed that the costeffectiveness ratio depends on the blood pressure reduction and the food costs, but is insensitive to dietician s time and drug costs. Overall, there were no significant changes in quality of life in terms of WHOQOL-BREF (HK) scores associated with either form of therapy. In the diet group, 94% found the low-salt diet acceptable. Subjects in the diet group were willing to pay more for the diet ($479.0±118.1 vs 430.4±75.4), although this finding was not statistically significant. Discussion Our study of nearly 200 subjects recruited from the general Table 4. Changes in measurements Measurement Diet group Mean±SE Drug group Mean±SE Baseline 3 Months 6 Months Baseline 3 Months 6 Months No. of subjects 38 33 31 36 31 31 Systolic blood pressure (mm Hg) 142±2.1 141±2.8 134±2.2 * 141±2.0 129±2.5 * 124±2.5 * Diastolic blood pressure (mm Hg) 95±1.3 91±1.6 * 88±1.3 * 95±1.0 86±1.7 * 84±1.8 * Heart rate (beats per minute) 69±1.2 68±1.6 68±1.5 71±1.5 67±1.5 69±1.6 24-h Na + (mmol/day) 190.7±14.5 154.2±13.6 * 201.2±15.9 200.4±13.6 164.0±11.1 * 179.7±13.3 24-h K + (mmol/day) 46.5±3.0 47.9±3.0 55.7±3.9 * 54.2±4.7 49.5±3.8 49.3±4.0 Body mass (kg) 67.5±2.1 66.0±2.0 65.6±2.0 * 68.8±2.4 67.3±2.2 67.2±2.2 Left ventricular mass index (g/m 2 ) 128.7±4.8-124.9±4.3 129.3±5.6-123.6±4.8 * P<0.05 vs baseline P<0.05 diet vs drug groups 34 Hong Kong Med J Vol 13 No 4 Supplement 4 August 2007

Cost-effectiveness of low-salt diet for lowering blood pressure Change in ambulatory blood pressure (mm Hg) 10 0-10 -20-30 -40-200 r=0.44, P=0.02 Diet group subjects Drug group subjects -100 0 100 200 300 Change in sodium excretion (mmol/day) Fig 2. Correlation of ambulatory blood pressure and sodium intake population showed that the correlation between sodium excretion and blood pressure is weak. This correlation is stronger among hypertensive subjects. This is an expected finding because not everyone in the general population who has a high-salt intake will develop hypertension. What clearly emerged from our study was the strong relationship between blood pressure and obesity, especially the waist circumference. This is consistent with clinical studies showing that weight control is by far the most effective non-pharmacological means of lowering blood pressure. In our randomised controlled trial of a low-sodium diet, we showed that the diet achieved a reduced sodium intake and urinary sodium excretion and that there were significant reductions in both systolic and diastolic blood pressure. Moreover, the reduction in diastolic blood pressure correlated with the reduction in sodium intake. Nonetheless, although blood pressure levels decreased significantly in both groups, there was a much greater decrease in blood pressure levels in the group allocated to drug treatment. Most patients randomised to the low-sodium diet group eventually required drug treatment to bring their blood pressure down to the target level. Non-pharmacological treatment can still enhance the effects of drug therapy, resulting in a lighter drug regimen and fewer side-effects. A diet that is not only low in sodium but also rich in fruit and vegetables might be more effective. Moreover, the healthy diet and lifestyle approach addresses not only high blood pressure but also other cardiovascular risk factors such as obesity, glucose tolerance, and dyslipidaemia. Our economic analysis found that the low-sodium diet and drug therapy were equally cost-effective. We used upper and lower 95% confidence limits to test the robustness of the cost-effectiveness ratios and found that they were mainly sensitive to the degree of blood pressure reduction and change in the cost of food. Due to the limited size of our study and the entry criteria for a clinical trial, our estimate of the effect size, ie the reduction in blood pressure, is subject to error. Caution must be exercised if extrapolating our findings to the community and generalising our conclusions. Nevertheless, our analysis of the costs of the low-sodium diet showed that savings in drug costs offset the cost of the dietician s time. It is sometimes argued that special diets are less affordable, but patients in the diet group reported a decrease in the costs of food. This suggests that for the Hong Kong Chinese population, a low-sodium diet does not cost more. Moreover, the dietary restrictions did not decrease quality of life and nearly all patients in the low-sodium diet group found the regimen acceptable. Conclusions As a reduction in blood pressure is related to a reduction in sodium intake, hypertensive patients able to reduce their sodium intake should be able to lower their blood pressure. A low-sodium diet reduces blood pressure to a lesser extent than antihypertensive drugs but this reduction may be sufficient for patients with mild hypertension. In patients with more severe hypertension, dietary sodium reduction is a safe, cost-effective complement to drug therapy. The low-sodium diet should be part of a calorie-controlled diet Table 5. Cost-effectiveness of low-salt diet versus drug therapy Mean±SD Low-salt diet Drug therapy P value No. of subjects 32 29 - Dietician s time (3 visits, $/subject) 146.3±8.3 - - Doctor s time (2 visits, $/subject) 107.8±6.3 98.4±6.3 - Cost of drugs ($/subject) 30.4±9.3 157.7±28.1 <0.001 Cost of laboratory test (renal function test, $/subject) 480 480 - Health service cost ($/subject) 764.5±13.9 736.1±29.5 0.39 Change in cost of food ($/subject) -357.3±152.0-137.4±97.5 - Cost of food supplements ($/subject) 47.8±37.7 - - Cost of lifestyle changes ($/subject) 25.0±19.6 53.1±53.1 - Travelling costs ($/subject) 111.7±11.8 123.0±15.0 - Patients costs ($/subject) -172.8±162.8 38.7±85.4 0.26 Total cost ($/subject) 591.6±163.4 774.8±75.0 0.31 Fall in diastolic blood pressure (mm Hg) 7.4±1.4 11.1±1.9 0.12 Cost-effectiveness ratio ($/mm Hg fall in diastolic blood pressure) * 103.1±56.7 69.6±39.6 0.64 * Cost-effectiveness ratios were calculated for each individual Hong Kong Med J Vol 13 No 4 Supplement 4 August 2007 35

Cheung et al rich in fruits and vegetables. In terms of public health, a healthy diet and lifestyle may reduce the prevalence of hypertension. Acknowledgements This study was supported by the Health Services Research Fund (#811028). Georgina Ho, Fefe Law, Jessica Lo, and Dickie Man were also part of the project team; their invaluable contribution is gratefully acknowledged. Permission to use the WHOQOL-BREF (HK) questionnaire was kindly given by Mr KF Leung, project manager of the project team responsible for the development of the Chinese version of the WHOQOL scale. References 1. Janus ED, Cockram CS, Fielding R, Hedley AJ, Ho P, Lam KS. The Hong Kong cardiovascular risk factor prevalence study 1995-1996. Hong Kong: Department of Clinical Biochemistry, Queen Mary Hospital of Hong Kong; 1997. 2. Intersalt Cooperative Research Group. Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24-hour urinary sodium excretion and potassium excretion. BMJ 1988;297:319-28. 3. Beard TC, Blizzard L, O Brien DJ, Dwyer T. Association between blood pressure and dietary factors in the dietary and nutritional survey of British adults. Arch Intern Med 1997;157:234-8. 4. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? I Analysis of observational data among populations. BMJ 1991;302:811-5. 5. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? II Analysis of observational data within populations. BMJ 1991;302:815-8. 6. Law MR, Frost CD, Wald NJ. By how much does dietary salt reduction lower blood pressure? III Analysis of data from trials of salt reduction. BMJ 1991;302:819-24. 7. Cheung BM, Ho SP, Cheung AH, Lau CP. Diastolic blood pressure is related to urinary sodium excretion in hypertensive Chinese patients. QJM 2000;93:163-8. 36 Hong Kong Med J Vol 13 No 4 Supplement 4 August 2007