Inflammation-Sensitive Plasma Proteins, Diabetes, and Mortality and Incidence of Myocardial Infarction and Stroke: A Population-Based Study

Pathophysiology

Inflammation-Sensitive Plasma Proteins, Diabetes, and Mortality and Incidence of Myocardial Infarction and Stroke

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FIG. 1.
Prevalence of diabetes in relation to BMI in men with zero to one (□) or two to five (▪) ISPs in the top quartile.
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FIG. 2.
Mean HOMA-IR (log transformed) in relation to BMI in men with zero to one (□) or two to five (▪) ISPs in the top quartile.
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FIG. 3.
RRs of cardiovascular mortality, cardiac events, and stroke in nondiabetic (ND) and diabetic (DM) men with low (I−) and high (I+) ISP levels. Adjusted for age, BMI, smoking, tobacco consumption, cholesterol, triglycerides, physical inactivity, systolic blood pressure, and medication for hypertension.

TABLE 1

Prevalence of cardiovascular risk factors in relation to diabetes and zero to one versus two to five elevated ISPs

	No diabetes			Diabetes
		Zero to one ISP in top quartile	Two to five ISPs in top quartile	Zero to one ISP in top quartile	Two to five ISPs in top quartile
n	3,808	1,921	186	135
Age (years)	46.7 ± 3.6	47.1 ± 3.8	46.4 ± 4.3	47.5 ± 4.3
BMI (kg/m²)	24.8 ± 3.1	24.9 ± 3.4	26.2 ± 4.0	27.9 ± 4.8
Cholesterol (mmol/l)	5.6 ± 1.0	5.8 ± 1.1	5.8 ± 1.4	5.8 ± 1.1
Triglycerides (mmol/l)	1.5 ± 0.8	1.7 ± 1.0	2.3 ± 3.1	2.5 ± 1.7
Creatinine (μmol/l)	94 ± 19	94 ± 22	93 ± 13	93 ± 14
Systolic BP (mmHg)	128 ± 15	129 ± 16	136 ± 17	139 ± 19
Diastolic BP (mmHg)	87 ± 10	87 ± 10	89 ± 11	92 ± 12
Smokers (%)	38	69	36	61
Physical inactivity (%)	19	24	21	21
Self-reported diabetes [n (%)]			35 (19)	30 (22)

TABLE 2

Prevalence of diabetes in relation to ISP levels and BMI

	BMI (kg/m²)				All men
		<25	25–29.9	≥30	All men
n	3,297	2,318	435	6,050
Men with diabetes (n)	118	130	73	321
Fibrinogen Q1–3 vs. Q4 (% with diabetes)	3.4 vs. 4.2	4.8 vs. 7.8	14.2 vs. 21.6	4.6 vs. 7.3
Haptoglobin Q1–3 vs. Q4 (% with diabetes)	3.7 vs. 3.2	4.7 vs. 8.4	14.8 vs. 21.6	4.8 vs. 6.7
Ceruloplasmin Q1–3 vs. Q4 (% with diabetes)	3.4 vs. 4.2	5.3 vs. 6.7	16.3 vs. 18.4	5.0 vs. 6.3
Orosomucoid Q1–3 vs. Q4 (% with diabetes)	3.9 vs. 2.7	5.1 vs. 6.9	14.6 vs. 20.9	5.0 vs. 6.1
α1-Antitrypsin Q1–3 vs. Q4 (% with diabetes)	3.4 vs. 3.9	5.4 vs. 6.2	15.9 vs. 19.2	5.1 vs. 5.8
No ISP in top Q (% with diabetes, n/n)	3.3 (45/1,373)	3.8 (35/930)	13.9 (19/137)	4.1 (99/2,440)
One ISP in top Q (% with diabetes, n/n)	4.0 (33/816)	6.3 (39/621)	12.8 (15/117)	5.6 (87/1,554)
Two ISPs in top Q (% with diabetes, n/n)	3.3 (16/490)	6.7 (23/341)	20.8 (15/72)	6.0 (54/903)
Three ISPs in top Q (% with diabetes, n/n)	5.4 (16/299)	6.9 (16/231)	16.9 (10/59)	7.1 (42/589)
Four or five ISPs in top Q (% with diabetes, n/n)	2.5 (8/319)	8.7 (17/195)	28.0 (14/50)	6.9 (39/564)
Zero to one ISP in top Q (% with diabetes)	3.6	4.8	13.4	4.7
Two to five ISPs in top Q (% with diabetes)	3.6	7.3	21.5	6.6
Adjusted OR for diabetes in men with two to five ISPs*	1.09 (0.72–1.6)	1.64 (1.13–2.4)	1.74 (1.03–3.0)	1.39 (1.09–1.77)

*
* Adjusted for age, physical activity, smoking, and BMI (all men only). OR, odds ratio; Q, quartile.

TABLE 3

All-cause and cardiovascular death and incidence of myocardial infarction and stroke in relation to diabetes and ISPs

	No diabetes			Diabetes
		Zero to one ISP in top quartile	Two to five ISPs in top quartile	Zero to one ISP in top quartile	Two to five ISPs in top quartile
n	3,808	1,921	186	135
All-cause mortality (n)	416	410	38	46
Age-adjusted RR	reference	2.1 (1.8–2.4)	2.1 (1.5–2.9)	3.8 (2.8–5.1)
Risk factor adjusted*	reference	1.6 (1.4–1.8)	1.8 (1.3–2.6)	2.5 (1.8–3.5)
Age-adjusted RR			reference	1.8 (1.2–2.8)
Risk factor adjusted*			reference	1.5 (0.93–2.4)
CVD mortality (n)	159	174	16	23
Age-adjusted RR	reference	2.3 (1.9–2.9)	2.3 (1.4–3.9)	4.9 (3.2–7.6)
Risk factor adjusted*	reference	1.7 (1.4–2.2)	1.8 (1.1–3.0)	2.8 (1.8–4.5)
Age-adjusted RR			reference	2.2 (1.1–4.1)
Risk factor adjusted†			reference	2.2 (1.2–4.2)
Cardiac events (n)	277	280	21	30
Age-adjusted RR	reference	2.2 (1.8–2.6)	1.7 (1.1–2.7)	3.7 (2.6–5.4)
Risk factor adjusted*	reference	1.6 (1.3–1.9)	1.3 (0.83–2.1)	2.2 (1.5–3.2)
Age-adjusted RR			reference	2.2 (1.2–3.8)
Risk factor adjusted†			reference	2.2 (1.2–3.8)
Stroke (n)	122	94	8	13
Age-adjusted RR	reference	1.7 (1.3–2.2)	1.5 (0.8–3.2)	3.9 (2.2–6.9)
Risk factor adjusted*	reference	1.4 (1.1–1.9)	1.2 (0.6–2.5)	2.5 (1.4–4.6)
Age-adjusted RR†			reference	2.4 (0.98–5.8)
Ischemic stroke (n)	100	80	8	11
Age-adjusted RR	reference	1.7 (1.3–2.3)	1.9 (0.91–3.8)	4.0 (2.1–7.4)
Risk factor adjusted*	reference	1.4 (1.0–1.9)	1.5 (0.7–3.1)	2.5 (1.3–4.8)
Age-adjusted RR			reference	2.0 (0.80–5.0)

*
* RR adjusted for age, BMI, smoking, tobacco consumption, cholesterol, triglycerides, physical inactivity, systolic blood pressure, and medication for hypertension.
†
† Number of covariables were reduced in a backward stepwise Cox regression due to the small number of events. Age, cholesterol, and ISP levels remained in the final models for cardiovascular death and cardiac events. Age and ISP levels remained in the final model for stroke.