Clinical Demography Characteristics, Routine and Advanced Lipid Indexes
300 patients were enrolled in this study, among which, 242 patients were diagnosed with CHD and assigned to CHD Group, 123 patients were diagnosed with DM and 75 patients were diagnosed with MS, assigned to DM Group and MS Group (Table 1). As the Supplement Table 1 ~ 3 showed, 9 clinical information and 139 NMR results were listed and compared between CHD Group and non-CHD Group, DM Group and non-DM Group, MS Group and non-MS Group. Among the variables, age, fasting plasma glucose (FPG), LDL particle/concentration (P/C) discordance, apolipoprotein A2 (ApoA2), apolipoprotein B (ApoB), total particles, LDL-6 particle, HDL-PL, LDL-6-TG, LDL-6-CE, LDL-6-FC, LDL-6-PL, LDL-6-ApoB, HDL-3-PL, HDL-2-apolipoprotein A1 (ApoA1) and HDL-3-ApoA1 were the items with difference in all the three comparisons, among which, ApoA2, HDL-PL, HDL-3-PL, HDL-2-ApoA1 and HDL-3-ApoA1 were significantly lower in CHD, DM and MS groups.
Table 1
Clinical Demography Characteristics, Routine and Advanced Lipids
|
non-CHD Group
(n = 58)
|
CHD Group(n = 242)
|
T / χ2
|
P
|
Age, y
|
58.86 ± 8.03
|
65.76 ± 8.46
|
5.628
|
< 0.001
|
Smoking, No.
|
7 (12.07%)
|
18 (7.44%)
|
1.708
|
0.252
|
Overweight a, No.
|
19 (32.76%)
|
65 (26.86%)
|
1.327
|
0.369
|
Diabetes, No.
|
19 (32.76%)
|
104 (42.98%)
|
2.022
|
0.155
|
Hypertension, No.
|
34 (58.62%)
|
143 (59.09%)
|
0.981
|
0.948
|
Family history b, No.
|
11 (18.97%)
|
37 (15.29%)
|
1.297
|
0.493
|
TG(mg/dL)*
|
133.92 (106.85, 200.46)
|
148.82 (100.94, 209.08)
|
0.394
|
0.694
|
ApoA1(mg/dL)
|
134.31 ± 15.94
|
130.41 ± 15.74
|
1.693
|
0.092
|
ApoB(mg/dL)*
|
77.91 (58.51,89.86)
|
82.10 (68.75,98.49)
|
2.839
|
0.005
|
TC-p(nmol/L)*
|
1416.58 (1063.81, 1633.81)
|
1492.63 (1250.06, 1790.84)
|
2.839
|
0.005
|
TC(mg/dL)
|
168.16 ± 38.43
|
177.74 ± 38.68
|
1.696
|
0.091
|
Lp(a)-p(nmol/L)*
|
42.80 (16.35, 93.88)
|
36.40 (13.40, 80.00)
|
0.801
|
0.424
|
Lp(a)(mg/dL)*
|
17.83 (6.81, 39.12)
|
14.96 (5.42, 33.12)
|
0.801
|
0.424
|
LDL-p(nmol/L)
|
1042.17 ± 360.58
|
1168.91 ± 366.35
|
2.374
|
0.018
|
LDL-C(mg/dL)
|
81.15 ± 32.77
|
87.30 ± 30.60
|
1.354
|
0.177
|
LDL-size(nm)*
|
20.44 (20.23, 20.68)
|
20.37 (20.17, 20.61)
|
1.634
|
0.103
|
LDL-p-corr(nmol/L)
|
977.50 ± 357.33
|
1108.44 ± 366.46
|
2.456
|
0.015
|
LDL-C-corr(mg/dL)
|
73.10 ± 32.30
|
79.76 ± 30.41
|
1.481
|
0.140
|
HDL-p(nmol/L)*
|
73.35 (45.78, 121.62)
|
78.87 (51.55, 114.60)
|
0.747
|
0.455
|
HDL-C(mg/dL)*
|
45.81 (38.86, 55.28)
|
45.23 (40.46, 50.51)
|
0.877
|
0.381
|
non-HDL-p(nmol/L)
|
1300.29 ± 381.68
|
1463.23 ± 424.55
|
2.675
|
0.008
|
non-HDL-p-corr(nmol/L)
|
1235.62 ± 377.88
|
1402.76 ± 426.11
|
2.740
|
0.007
|
non-HDL-C(mg/dL)
|
120.62 ± 34.74
|
131.50 ± 37.68
|
2.004
|
0.046
|
non-HDL-C-corr(mg/dL)*
|
112.53 (84.79, 136.45)
|
116.96 (96.00, 147.17)
|
2.148
|
0.033
|
a, Overweight was defined as body mass index (BMI) > 28 (BMI = weight (Kg) / height (m)). b, Family history was defined as the age of onset of coronary heart disease less than 55 for men and less than 65 for women, in the immediate family members of patients. |
TG, triglyceride; ApoA1, apolipoprotein A1; ApoB, apolipoprotein B; TC-p, total particles of cholesterol; TC, total cholesterol; Lp(a), lipoprotein a; Lp(a)-p, particles of Lp(a); LDL-C, low-density lipoprotein cholesterol; LDL-p, particles of LDL; LDL-size, average diameter of LDL-p; LDL-p-corr and LDL-C-corr, corrected LDL-p and LDL-C; HDL-C, high-density lipoprotein cholesterol; HDL-p, particles of HDL; non-HDL-C, none high-density lipoprotein cholesterol; non-HDL-p, particles of non-HDL; non-HDL-p-corr and non-HDL-C-corr, corrected non-HDL-p and non-HDL-C. |
Lp(a) = Lp(a)-p*0.4167; LDL-p-corr = LDL-p – Lp(a)-p; LDL-C-corr = LDL-C – 0.3*Lp(a); non-HDL-p = TC-p – HDL-p; non-HDL-p-corr = non-HDL-p – Lp(a)-p; Non-HDL-C = TC – HDL-C; non-HDL-C-corr = non-HDL-C – 0.3*Lp(a) |
TG, ApoB, TC-p, Lp(a)-p, Lp(a), LDL-C-size, HDL-C-p, HDL-C and non-HDL-C-corr were skew distribution and shown as median (25th percentile, 75th percentile). Before the Student’s t-test for the difference between groups, the nonnormal distribution variables were converted into natural logarithm form. |
As shown in Supplement Table 1, the particles of LDL, not the concentration, was significantly higher in CHD group. Further comparison showed that the difference was mainly caused by the particles of LDL-1 and LDL-6. In the comparison between DM and non-DM patients, shown in Supplement Table 2, IDL -PL and VLDL-PL were much higher in DM patients, HDL-FC were much lower in DM patients. Most of the NMR measured lipid indexes were different between MS patients and non-MS patients, as shown in Supplement Table 3. Despite the characteristics presented in the comparison between CHD patients and non-CHD patients, DM patients and non-DM patients, the comparison between MS patients and non-MS patients also showed that VLDL-PL, IDL-PL, LDL-PL and HDL-TG were much higher in MS patients, while HDL-CE and HDL-FC were much lower in MS patients. (Supplement Table 3) Compared with undiagnosed population, PCSK9 were lower in CHD patients and MS patients.
Risk Factors of CHD
As Fig. 2 showed the result of multiple Logistic regression, age (hazard ratio (HR) = 2.520, 95% confidence interval (CI): 1.081 ~ 5.086, P = 0.032), the particle of LDL-6 (HR = 1.006, 95% CI: 1.001 ~ 1.012, P = 0.022), LDL-TG (HR = 1.200, 95% CI: 1.034 ~ 1.393, P = 0.016) and LDL-FC (HR = 1.330, 95% CI: 1.142 ~ 1.549, P < 0.001) were risk factors of CHD. While, ethanol (HR = 0.862, 95% CI: 0.745 ~ 0.996, P = 0.044) and glycerol (HR = 0.114, 95% CI: 0.021 ~ 0.609, P = 0.011) were the protective factors of CHD. Even with no statistical significance, PCSK9 had a neutral effect on CHD.
The Relation between Gensini and NMR Results
Heatmaps, Figs. 3 and 4, showed the direction and intensity of the Spearman correlation between Gensini and NMR results as well as PCSK9 and NMR results, in all postmenopausal women and the patients diagnosed with CHD, DM, and MS.
In general, Fig. 3 showed that the positive correlation between Gensini and NMR results deposited in VLDL-2 ~ VLDL-5, IDL, LDL-1 and LDL-2, while the negative correlations concentrated on ApoA1, ApoA2 and HDL-1 ~ HDL-4.
In all postmenopausal women enrolled in this study, the indexes with positive correlation with Gensini including ApoB/A1, particles of VLDL and IDL, lipoprotein contents TG in VLDL-3 ~ VLDL-5, LDL-1 ~ LDL-2, LDL-5 ~ LDL-6, CE in VLDL-2 ~ VLDL4, IDL, FC in VLDL-2 ~ VLDL-4, IDL and LDL-1 and PH in VLDL-3 ~ VLDL-5, while the indexes with negative correlation were ApoA1, ApoA2, ApoA1, CE and PL in HDL-2 ~ HDL-4, FC in HDL-3 and ApoA2 in HDL-4. The NMR results of CHD and DM patients showed a similar but not identical trends with All patients. In the MS patients, the indexes positively related to Gensini were confined only to the TG, CE and PL in VLDL-3 ~ VLDL-5, while the negative correlated indexes were ApoA1, FC and PL in LDL-1, and ApoA1, CE, PL in HDL-1. The PCSK9 was negatively correlated with Gensini in all patients and DM patients.
The Relation between PCSK9 and NMR Results
Figure 4 showed correlations between plasma PCSK9 and NMR results. In all patients and CHD, DM subgroups, PCSK9 showed a similar trend that negatively correlated with total cholesterol (TC), ApoB/A1, the particles of VLDL, IDL and LDL, as well as nearly all the lipid contents in VLDL-3 ~ VLDL-5, IDL and LDL-1. In MS group, there was little correlation between PCSK9 and NMR results.