Assessment of Cardiovascular Risk Factors and Their Interactions in the Risk of Coronary Heart Disease in Patients with Type 2 Diabetes with Different Weight Levels, 2013–2018

Figures & data

Figure 1 Flowchart of study participants.

Table 1 Descriptive Characteristics of the Study Sample at Classified by BMI

	Low Weight (<18.5kg/m^2) n=967	Normal Weight (18.5–24.9 kg/m^2) n=14,443	Overweight (25.0–29.9 kg/m^2) n=12,204	Mild Obesity (30.0–34.9 kg/m^2) n=2769	Severe Obesity (≥35.0 kg/m^2) n=310	P value
Female, n (%)	488(50.5)^a	6493(45)	5451(44.7)	1374(49.6)^a	178(57.4)^a	<0.001
Age (year)	71.5±12.5^a	68.4±12.4	66.8±12.9^a	65.0±14.7^a	61.9±17.1^a	<0.001
Diabetes duration (y)	8.5±3.7^a	8.0±3.4	7.8±3.3^a	7.7±3.8^a	6.7±3.8^a	<0.001
Hypertension, n (%)	506(52.3)^a	8784(60.8)	8581(70.3)^a	2170(78.4)^a	246(79.4)^a	<0.001
CHD, n (%)	268(27.7)^a	3235(22.4)	2852(23.4)	758(27.4)^a	89(28.7)	<0.001
Smoking, n (%)	162(16.9)^a	3017(21.2)	2831(23.5)^a	716(26.2)^a	80(26.6)	<0.001
Drinking, n (%)	69(7.2) ^a	1656(11.6)	1656(13.7)^a	415(15.2)^a	44(14.6)	<0.001
BMI (kg/m^2)	17.1±1.2^a	22.5±1.7	27.0±1.4^a	31.6±1.3^a	37.4±3.6^a	<0.001
Antiplatelet user, n (%)	450(52.4)	6309(49.0)	5453(50.3)	1235(50.6)	135(48.7)	0.112
Statin user, n (%)	338(39.4)	5192(40.3)	4407(40.7)	978(40.1)	111(39.8)	0.944
Insulin user, n (%)	518(60.4)	7984(61.9)	6647(61.2)	1434(58.5)^a	164(58.8)	0.028
Metformin user, n (%)	162(18.9)^a	2972(23.0)	2711(25.0)^a	593(24.2)	70(25.1)	<0.001
FBG (mmol/L)	10.4±5.8	10.2±5.3	10.1±4.9	10.2±4.7	10.2±5.4	0.125
HbA1c (%)	8.3±2.4	8.2±2.2	8.1±2.0^a	8.1±2.0	8.1±2.0	0.010
Hypoglycemia, n (%)	17(1.8)	179(1.3)	128(1.1)	19(0.7)^a	3(1.0)	0.032
T-CHO (mmol/L)	4.3±1.2^a	4.5±1.4	4.5±1.3^a	4.6±1.3^a	4.6±1.2	<0.001
HDL-C (mmol/L)	1.2±0.3^a	1.1±0.3	1.1±0.3^a	1.1±0.3^a	1.1±0.3	<0.001
LDL-C (mmol/L)	2.6±0.9^a	2.7±0.9	2.8±1.0^a	2.8±0.9^a	2.8±1.0	<0.001
Triglyceride (mmol/L)	1.2 (0.8–1.7)^a	1.4 (1.0–2.1)	1.6 (1.1–2.3)^a	1.7 (1.2–2.5)^a	1.8 (1.3–2.5)^a	<0.001
Apolipoprotein-A1 (g/L)	1.1±0.3	1.1±0.3	1.1±0.3^a	1.1±0.3^a	1.1±0.3	0.023
Apolipoprotein-B (g/L)	0.8±0.2^a	0.8±0.2	0.8±0.3^a	0.8±0.2^a	0.8±0.3	<0.001
Lipoprotein-a (mg/L)	232 (117.5–400.5)^a	197 (103–349)	186 (97–330.5)^a	182 (99–326)^a	160 (73.8–318.3)^a	<0.001
BUN (mmol/L)	7.3±5.1^a	6.8±4.6	6.7±4.5	6.7±4.6	6.8±4.6	0.003
SCr (umol/L)	73 (60–95)	74 (61–92)	76 (63–94)^a	75 (62–94)^a	74 (60–92.5)	<0.001
SUA (umol/L)	272.2±131.7^a	289.3±121.3	305.3±123.2^a	313.1±133.2^a	334.4±143.8^a	<0.001

Notes: Data are mean±SD, median (interquartile range), or n (%). ^ap < 0.05 compared to Normal weight group.

Abbreviations: BMI, body mass index; CHD, coronary heart disease; FBG, fasting blood-glucose; HbA1c, glycosylated hemoglobin; T-CHO, total cholesterol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; BUN, blood urea nitrogen; SCr, serum creatinine; SUA, serum uric acid.

Table 2 Incidence Rates and ORs for CHD According to BMI by History of HP in Patients with Type 2 Diabetes

	Low Weight (<18.5 kg/m^2)	Normal Weight (18.5–24.9 kg/m^2)	Overweight (25.0–29.9 kg/m^2)	Mild Obesity (30.0–34.9 kg/m^2)	Severe Obesity (≥35.0 kg/m^2)
Prevalence, n (%)
HP	216(42.7)	2550(29.0)	2382(27.8)	685(31.6)	83(33.7)
No-HP	52(11.3)	685(12.1)	470(13.0)	73(12.2)	6(9.4)
OR (95% CI)
Basic regression model^a
HP	1.67(1.37–2.03)	1.00 (Ref)	1.02(0.95–1.09)	1.28(1.14–1.42)	1.68(1.26–2.25)
No-HP	0.74(0.54–1.01)	1.00 (Ref)*	1.25(1.1–1.43)	1.54(1.17–2.03)	1.84(0.74–4.55)
Main regression model^b
HP	1.78(1.43–2.23)	1.00 (Ref)	1.05(0.96–1.13)	1.27(1.12–1.44)	1.72(1.24–2.39)
No-HP	0.62(0.44–0.88)	1.00 (Ref)*	1.30(1.12–1.51)	1.69(1.23–2.31)	2.51(0.85–7.42)

Notes: ^aBasic models include adjustment for sex, age, and diabetes duration. ^bMain models additionally include smoking, drinking, use of antiplatelet, statin, insulin, and metformin, FBG, HbA1c, hypoglycemia, total cholesterol, LDL-C, triglyceride, lipoprotein-a, SCr, and SUA; *The same model as for HP group except patients without hypertension and BMI 18.5–24.9 kg/m² constitute the reference group.

Abbreviations: CHD, coronary heart disease; BMI, body mass index; HP, hypertension; Ref, reference group; FBG, fasting blood-glucose; HbA1c, glycosylated hemoglobin; LDL-C, low-density lipoprotein cholesterol; SCr, serum creatinine; SUA, serum uric acid.

Figure 2 Prevalence of coronary heart disease in patients with type 2 diabetes by cardiovascular risk factors and body mass index levels. Patients were classified according to the history of hypertension (A), HbA1c (B), Lpa (C) and smoking (D).

Abbreviations: CHD, coronary heart disease; BMI, body mass index; HbA1c, glycosylated hemoglobin; Lpa, lipoprotein-a.

Figure 3 Additive interaction of BMI and hypertension on risk of CHD by BMI presented as odds ratio partitioned into relative excess risks due to BMI, hypertension, and their interaction.

Notes: All ORs are adjusted for sex, age, diabetes duration, smoking, drinking, use of antiplatelet, statin, insulin, and metformin, FBG, HbA1c, hypoglycemia, total cholesterol, LDL-C, triglyceride, lipoprotein-a, SCr, and SUA.
Abbreviations: BMI, body mass index; CHD, coronary heart disease; HP, hypertension; U, BMI 18.5 to <25.0 kg/m² and without hypertension; RERI, relative excess risk due to interaction; FBG, fasting blood-glucose; HbA1c, glycosylated hemoglobin; LDL-C, low-density lipoprotein cholesterol; SCr, serum creatinine; SUA, serum uric acid.

Table 3 Statistics for Additive Interaction Between BMI and HP in Multivariable-Adjusted Models of Incident CHD in Patients with Type 2 Diabetes Mellitus

	BMI Category (kg/m^2)
Additive Interaction Statistic	Low Weight (<18.5)	Normal Weight (18.5–24.9)	Overweight (25.0–29.9)	Mild Obesity (30.0–34.9)	Severe Obesity (≥35.0)
RERI (95% CI)	2.19(0.88, 3.50)	Reference*	−0.16(−0.52, 0.20)	0.10(−0.71, 0.91)	0.75(−2.64, 4.14)
Attributable proportion^a (95% CI)	0.52(0.35, 0.69)	Reference*	−0.07(−0.21, 0.08)	0.03(−0.24, 0.31)	0.18(−0.59, 0.95)
Synergy index (95% CI)	3.11(1.75, 5.53)	Reference*	0.90(0.72, 1.12)	1.05(0.69, 1.62)	1.31(0.35, 4.89)

Notes: *The reference group is patients with BMI 18.5–24.9 kg/m² and without HP. ^aThe proportion of CHD risk that is attributable to the additive interaction between BMI and hypertension.

Abbreviations: BMI, body mass index; CHD, coronary heart disease; HP, hypertension; RERI, relative excess risk due to interaction.