**5. Implications for management and prevention of dyslipidaemia**

Epidemiological investigations of human populations have revealed a robust relationship between lipids and CVD risk. Furthermore, the benefit of lipid-modifying strategy on cardiovascular events has been demonstrated from a large number of randomized clinical trials (Thavendiranathan et al. 2006; Mills et al. 2008), especially from those using 3 hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (i.e., statins) (Goldberg, R. B. et al. 1998; Collins et al. 2003; Colhoun et al. 2004; Pyorala et al. 2004; Sever et al. 2005; Knopp et al. 2006; Shepherd et al. 2006). Intensive control of dyslipidaemia has been greatly emphasized in the prevention and management of CVD. Current guidelines from the National Cholesterol Education Program Adult Treatment Panel III (ATP III) (Adult Treatment Panel III 2002), the European Society of Cardiology (Graham et al. 2007) and the American Diabetes Association (American Diabetes Association 2009) consistently

Ethnic Difference in Lipid Profiles 23

Model adjusted for age, study cohort, body mass index, systolic blood pressure and smoking status.

Table 1. Odds ratio (95% confidence interval) of having dyslipidaemia in relation to

NFG, normal fasting glucose; NGT, normal glucose tolerance. a Reference group

ethnicity by glucose categories.

Fig. 1. Age-, study cohort- and body mass index-adjusted mean lipid (geometric means for triglycerides) and lipoprotein concentrations and 95% CIs (vertical bars) in men (figure 1-a, c, e and g) and women (figure 1-b, d, f and h) by ethnicities and glucose categories.\* p for trend < 0.05 within each glucose category.


Model adjusted for age, study cohort, body mass index, systolic blood pressure and smoking status. NFG, normal fasting glucose; NGT, normal glucose tolerance. a Reference group

Table 1. Odds ratio (95% confidence interval) of having dyslipidaemia in relation to ethnicity by glucose categories.

22 Dyslipidemia - From Prevention to Treatment

4,3 4,8 5,3 5,8 6,3 6,8

2 2,5 3 3,5 4 4,5

0,9 1 1,1 1,2 1,3 1,4 1,5 1,6 1,7 1,8

(h)

0,9 1 1,1 1,2 1,3 1,4

**Triglycerides (mmol/l)**

\*

**HDL-cholesterol (mmol/l)**

**LDL cholesterol (mmol/l)**

(f)

**Total cholesterol (mmol/l)**

\*

\*

\* (d)

(b)

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

\* \* \* \*

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

\*

\*

\*

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

\*

\*

\*

\*

\*

\*

\*

\*

\*

Fig. 1. Age-, study cohort- and body mass index-adjusted mean lipid (geometric means for triglycerides) and lipoprotein concentrations and 95% CIs (vertical bars) in men (figure 1-a, c, e and g) and women (figure 1-b, d, f and h) by ethnicities and glucose categories.\* p for

trend < 0.05 within each glucose category.

4,3 4,8 5,3 5,8 6,3 6,8

2 2,5 3 3,5 4 4,5

0,9 1 1,1 1,2 1,3 1,4 1,5 1,6 1,7 1,8

(g)

0,9 1 1,1 1,2 1,3 1,4

**Triglycerides (mmol/l)**

\*

**HDL-cholesterol (mmol/l)**

**LDL cholesterol (mmol/l)**

(e)

(c)

**Total cholesterol (mmol/l)**

(a)

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

\* \* \*

\*

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

\*

NFG and NGT IFG and/or IGT DM-Undiagnosed DM-Diagnosed

Central & Northern European Southern European Qingdao Chinese Mauritian Indian Hong Kong Chinese Japanese

\*

\*

Asian Indian

\* \*

\* \*

Ethnic Difference in Lipid Profiles 25

In contrast to LDL-C, HDL-C has been either dropped from (Graham et al. 2007) or set as a secondary (American Diabetes Association 2010) or tertiary (Expert Panel on Detection 2001) target in the major guidelines despite the strong evidence of reduced HDL-C as an independent risk factor for CVD (Boden 2000). This may change if more therapy choices developed to increase HDL-C levels and improve HDL function are shown to prevent CVD (Singh et al. 2007; Duffy and Rader 2009; Sorrentino et al. 2010) or reduce the residual cardiovascular risk (Fruchart J 2008). Most recently, the ARBITER 6-HALTS (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis) trial has shown a significant improvement in serum HDL-C levels and regression of carotid intima-media thickness when ERN was conbined with statin therapy in patients with CHD or CHD equivalent (Taylor et al. 2009; Villines et al. 2010). Considering the high proportion of Asian Indians with adverse HDL-C levels, appropriate approaches to increasing HDL-C and/or improving HDL function may become an important treatment target in Asian Indians in order to reduce their excess CVD

Total cholesterol High-density lipoprotein

cholesterol

Measured after precipitation of very-low density lipoprotein (VLDL) and low-density lipoprotein (LDL) by polyethylene glycol PEG 6000.

Enzymatic method after precipitation with dextran sulphate-MgCl2 on Cobas Mira analyzer (Hoffman-La Roche and Co., Basle

Enzymatic method after precipitation (AMS Analyzer Medical System, SABA-18, Rome, Italy)

Direct method (Olympus reagent) with OLYMPUS-AU640 Automatic Analyzers (Olympus Optical. Tokyo, Japan)

Switzerland)

Triglycerides

Lipase/glycerol kinase method;

Enzymatic method, with reagents (Baker Instruments Corporation, Allentown, PA 18103, USA) with Cobas Mira analyzer (Hoffman-La Roche and Co., Basle Switzerland)

Enzymatic method (AMS Analyzer Medical System, SABA-18, Rome,

Enzymatic method (Olympus reagent) with OLYMPUS-AU640 Automatic Analyzers (Olympus Optical. Tokyo, Japan)

Italy)

risks.

China Hong Kong Cardiovascular DiseaseRisk Factor Prevalence Study

**6. Appendix 1** 

Blood sample

Venous Plasma

Venous Plasma

Plasma Cholesterol oxidase

(CHOD) method; Hitachi 717 analyser (Hitachi Instruments, California, USA).

Enzymatic method, with reagents (Baker Instruments Corporation, Allentown, PA 18103, USA) with Cobas Mira analyzer (Hoffman-La Roche and Co., Basle Switzerland).

Enzymatic method (AMS Analyzer Medical System, SABA-18, Rome, Italy)

(Olympus reagent) With OLYMPUS-AU640 Automatic Analyzers (Olympus Optical. Tokyo, Japan)

Serum Enzymatic method

Countries and studies

Hong Kong Workforce Survey on CVD Risk Factors

Qingdao Diabetes Survey

Qingdao Diabetes Study

2002

2006


a < 1.03 mmol/l in men and < 1.29 mmol/l in women

b ≥ 1.70 mmol/l

Table 2. Proportions (%) of individuals according to lipid levels stratified by diabetic status in each ethnic group.

recommend that LDL-C should be the primary target of therapy not only in patients with CHD or diabetes but also in individuals with increased cardiovascular risk. In addition, non-HDL-C is set by ATP III as a secondary target of therapy and HDL-C and TG as potential target. The Current guideline, mainly based on the data of Whites, consistently recommend that LDL-C < 2.6 mmol/l should be the primary target of therapy in patients with diabetes. As shown in our study and others' (Mulukutla et al. 2008; Karthikeyan et al. 2009), the Asian Indian population had significantly lower TC and LDL-C than did Whites. The threshold of LDL-C for treatment target for Whites may be too high for Asian Indians. Further studies are warranted to verify this hypothesis and determine the threshold applicable to this ethnic group.

High TG b alone, %

Qingdao Chinese 31.0 5.4 8.3 1.9 40.5 2.4 9.8 0.7 Asian Indian 23.2 33.6 3.2 11.0 9.2 10.7 2.8 6.4 Mauritian Indian 23.9 15.8 5.0 4.7 23.2 14.7 5.7 7.0 Japanese 25.2 6.4 3.4 3.5 38.2 13.0 5.0 5.3

Qingdao Chinese 21.1 3.5 11.1 3.1 37.9 2.7 19.1 1.5 Asian Indian 12.8 17.4 6.0 21.4 8.1 12.4 7.2 14.7 Mauritian Indian 12.4 8.6 6.4 10.2 21.2 15.5 10.2 15.5 Japanese 14.3 6.0 7.1 5.1 34.3 11.6 12.2 9.4

Table 2. Proportions (%) of individuals according to lipid levels stratified by diabetic status

recommend that LDL-C should be the primary target of therapy not only in patients with CHD or diabetes but also in individuals with increased cardiovascular risk. In addition, non-HDL-C is set by ATP III as a secondary target of therapy and HDL-C and TG as potential target. The Current guideline, mainly based on the data of Whites, consistently recommend that LDL-C < 2.6 mmol/l should be the primary target of therapy in patients with diabetes. As shown in our study and others' (Mulukutla et al. 2008; Karthikeyan et al. 2009), the Asian Indian population had significantly lower TC and LDL-C than did Whites. The threshold of LDL-C for treatment target for Whites may be too high for Asian Indians. Further studies are warranted to verify this hypothesis and determine the threshold

Normal

Non-diabetic population Hong Kong Chinese

Central & Northern European

Southern European

Diabetic population Hong Kong Chinese

Central & Northern European

Southern European

b ≥ 1.70 mmol/l

in each ethnic group.

applicable to this ethnic group.

HDL-C and normal TG, %

a < 1.03 mmol/l in men and < 1.29 mmol/l in women

Low HDL-C a alone, %

LDL-C < 3 mmol/l LDL-C ≥ 3 mmol/l

29.3 9.9 1.6 4.2 32.1 12.9 3.7 6.2

13.3 2.3 2.0 1.6 48.6 9.7 12.6 10.0

14.2 4.3 1.1 2.1 45.5 15.1 7.8 10.0

12.4 9.6 1.4 11.0 22.6 18.1 7.6 17.2

10.5 2.8 4.9 6.4 30.4 9.3 16.4 19.4

7.5 3.3 6.0 10.2 24.4 11.2 12.8 14.8

Normal HDL-C and normal TG, %

Low HDL-C a alone, % High TG b alone, %

both, %

both, %

In contrast to LDL-C, HDL-C has been either dropped from (Graham et al. 2007) or set as a secondary (American Diabetes Association 2010) or tertiary (Expert Panel on Detection 2001) target in the major guidelines despite the strong evidence of reduced HDL-C as an independent risk factor for CVD (Boden 2000). This may change if more therapy choices developed to increase HDL-C levels and improve HDL function are shown to prevent CVD (Singh et al. 2007; Duffy and Rader 2009; Sorrentino et al. 2010) or reduce the residual cardiovascular risk (Fruchart J 2008). Most recently, the ARBITER 6-HALTS (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis) trial has shown a significant improvement in serum HDL-C levels and regression of carotid intima-media thickness when ERN was conbined with statin therapy in patients with CHD or CHD equivalent (Taylor et al. 2009; Villines et al. 2010). Considering the high proportion of Asian Indians with adverse HDL-C levels, appropriate approaches to increasing HDL-C and/or improving HDL function may become an important treatment target in Asian Indians in order to reduce their excess CVD risks.

