Risk characteristics of obesity and atherosclerotic cardiovascular events in patients with schizophrenia: A single-center 10-year retrospective cohort study

Table 1 Baseline demographic and clinical characteristics of our hospital cohort, n (%)/mean ± SD

Characteristic	Total cohort (n = 10000)	Obese (n = 4370)	Non-obese (n = 5630)	P value
Demographics
Age, years	42.3 ± 13.5	44.1 ± 12.8	40.9 ± 13.9	< 0.001
Male sex	5820 (58.2)	2234 (51.1)	3586 (63.7)	< 0.001
Race/ethnicity				0.002
White	4235 (42.4)	1789 (40.9)	2446 (43.4)
Black	2890 (28.9)	1342 (30.7)	1548 (27.5)
Hispanic	1876 (18.8)	856 (19.6)	1020 (18.1)
Asian	654 (6.5)	234 (5.4)	420 (7.5)
Other	345 (3.5)	149 (3.4)	196 (3.5)
Clinical characteristics
Schizophrenia subtype				0.134
Paranoid	5234 (52.3)	2289 (52.4)	2945 (52.3)
Disorganized	1876 (18.8)	834 (19.1)	1042 (18.5)
Catatonic	234 (2.3)	95 (2.2)	139 (2.5)
Undifferentiated	1543 (15.4)	678 (15.5)	865 (15.4)
Schizoaffective	1113 (11.1)	474 (10.8)	639 (11.4)
Duration of illness, years	12.8 ± 9.4	14.2 ± 9.8	11.7 ± 8.9	< 0.001
Hospitalizations at our facility	4.3 ± 3.8	4.9 ± 4.2	3.8 ± 3.4	< 0.001
PANSS total score	78.4 ± 18.2	76.2 ± 17.4	80.1 ± 18.7	< 0.001
GAF score	48.3 ± 12.1	46.9 ± 11.8	49.4 ± 12.2	< 0.001

PANSS: Positive and Negative Syndrome Scale; GAF: Global Assessment of Functioning.

Table 2 Baseline metabolic parameters and cardiovascular risk factors at our institution, n (%)/mean ± SD

Parameter	Total cohort (n = 10000)	Obese (n = 4370)	Non-obese (n = 5630)	P value
Anthropometric measures
BMI, kg/m2	29.8 ± 6.4	35.6 ± 5.2	25.3 ± 3.1	< 0.001
Waist circumference, cm	98.4 ± 16.2	110.2 ± 14.3	89.2 ± 11.4	< 0.001
Weight change from admission, kg	+18.3 ± 14.2	+28.4 ± 15.3	+10.4 ± 8.7	< 0.001
Metabolic syndrome components
Metabolic syndrome	3890 (38.9)	2543 (58.2)	1347 (23.9)	< 0.001
Hypertension	3456 (34.6)	1987 (45.5)	1469 (26.1)	< 0.001
Diabetes mellitus	1843 (18.4)	1123 (25.7)	720 (12.8)	< 0.001
Dyslipidemia	4123 (41.2)	2234 (51.1)	1889 (33.6)	< 0.001
Laboratory values
Fasting glucose, mg/dL	108.3 ± 32.4	116.7 ± 38.2	101.8 ± 26.3	< 0.001
HbA1c, %	6.1 ± 1.3	6.5 ± 1.5	5.8 ± 1.0	< 0.001
Total cholesterol, mg/dL	198.4 ± 42.3	204.3 ± 44.1	193.8 ± 40.2	< 0.001
LDL cholesterol, mg/dL	118.2 ± 35.4	122.4 ± 36.8	115.0 ± 34.0	< 0.001
HDL cholesterol, mg/dL	44.3 ± 13.2	41.2 ± 12.1	46.7 ± 13.6	< 0.001
Triglycerides, mg/dL	178.4 ± 98.3	204.3 ± 112.4	158.3 ± 82.1	< 0.001
Blood pressure
Systolic BP, mmHg	128.4 ± 18.2	132.3 ± 18.9	125.4 ± 17.1	< 0.001
Diastolic BP, mmHg	79.8 ± 11.3	82.1 ± 11.8	78.0 ± 10.6	< 0.001

HbA1c: Hemoglobin A1c; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; BP: Blood pleasure.

Table 3 Antipsychotic medication use patterns at our hospital at baseline, mean ± SD

Medication pattern	n (%)	Mean daily dose (CPZ equivalents)	Duration at our facility (years)
Treatment regimen
Monotherapy	5432 (54.3)	423 ± 234	4.3 ± 3.8
Polypharmacy (2 agents)	2456 (24.6)	612 ± 298	3.8 ± 3.2
Polypharmacy (≥ 3 agents)	846 (8.5)	834 ± 367	3.2 ± 2.9
No current antipsychotic	1266 (12.7)	-	-
Specific agents
Olanzapine	2134 (21.3)	489 ± 189	4.8 ± 4.1
Risperidone	1987 (19.9)	398 ± 156	4.2 ± 3.6
Quetiapine	1543 (15.4)	445 ± 234	3.9 ± 3.4
Aripiprazole	1234 (12.3)	367 ± 145	3.2 ± 2.8
Paliperidone	987 (9.9)	412 ± 178	2.8 ± 2.4
Clozapine	678 (6.8)	523 ± 212	5.6 ± 4.8
Haloperidol	567 (5.7)	389 ± 167	3.4 ± 3.1
Other	1604 (16.0)	401 ± 189	3.6 ± 3.2
Metabolic risk category
High risk	3890 (38.9)	478 ± 223	4.6 ± 3.9
Moderate risk	2987 (29.9)	412 ± 187	3.8 ± 3.3
Low risk	1857 (18.6)	378 ± 156	3.1 ± 2.7

CPZ: Chlorpromazine.

Table 4 Cardiovascular risk stratification in our hospital cohort at baseline, n (%)/mean ± SD

Risk assessment tool	Total cohort	Obese	Non-obese	P value
QRISK3 score
Mean 10-year risk (%)	12.8 ± 8.3	16.4 ± 9.2	10.0 ± 6.8	< 0.001
Low risk (< 10%)	4234 (42.3)	1234 (28.2)	3000 (53.3)	< 0.001
Moderate risk (10%-20%)	3876 (38.8)	1876 (42.9)	2000 (35.5)
High risk (> 20%)	1890 (18.9)	1260 (28.8)	630 (11.2)
Framingham risk score
Mean 10-year risk (%)	9.4 ± 6.7	11.8 ± 7.4	7.6 ± 5.6	< 0.001
Vascular age
Mean vascular age years	54.3 ± 14.2	58.2 ± 13.4	51.3 ± 14.1	< 0.001
Vascular age acceleration years	12.0 ± 8.4	14.1 ± 8.9	10.4 ± 7.6	< 0.001

Table 5 Incident cardiovascular events during 10-year follow-up at our institution, n (%)/hazard ratio (95% confidence interval)

Outcome	Total events	Incidence rate per 1000 person-years	Obese	P value
Primary composite outcome
MACE	1842 (18.4)	23.6	2.34 (2.11-2.59)	< 0.001
Individual components
Cardiovascular death	423 (4.2)	5.4	2.67 (2.18-3.27)	< 0.001
Myocardial infarction	678 (6.8)	8.7	2.23 (1.89-2.63)	< 0.001
Stroke	543 (5.4)	6.9	1.98 (1.64-2.39)	< 0.001
Heart failure hospitalization	456 (4.6)	5.8	2.89 (2.36-3.54)	< 0.001
Coronary revascularization	234 (2.3)	3.0	2.12 (1.61-2.79)	< 0.001
Secondary outcomes
All-cause mortality	1234 (12.3)	15.8	1.89 (1.68-2.13)	< 0.001
New-onset diabetes	1456 (17.8)1	22.9	3.12 (2.77-3.51)	< 0.001
New-onset hypertension	1876 (28.6)2	37.5	2.45 (2.21-2.71)	< 0.001

¹Among 8157 without baseline diabetes at our hospital.

²Among 6544 without baseline hypertension at our hospital.

MACE: Major adverse cardiovascular events.

Table 6 Metabolic parameter changes over 10-year follow-up at our institution, n (%)/mean ± SD

Parameter	Baseline	Year 2	Year 5	Year 10	P value
Weight and BMI
Mean weight, kg	84.3 ± 19.2	89.1 ± 20.4	91.2 ± 21.3	92.8 ± 22.1	< 0.001
Mean BMI, kg/m2	29.8 ± 6.4	31.5 ± 6.8	32.2 ± 7.1	32.8 ± 7.4	< 0.001
Obesity prevalence, %	43.7	52.3	58.4	62.1	< 0.001
Metabolic syndrome
Prevalence, %	38.9	46.2	52.8	58.3	< 0.001
Mean components, n	2.3 ± 1.4	2.7 ± 1.4	3.0 ± 1.4	3.2 ± 1.3	< 0.001
Glycemic control
Mean fasting glucose, mg/dL	108.3 ± 32.4	112.4 ± 34.8	115.8 ± 36.2	118.9 ± 38.4	< 0.001
Mean HbA1c, %	6.1 ± 1.3	6.3 ± 1.4	6.5 ± 1.5	6.7 ± 1.6	< 0.001
Diabetes prevalence, %	18.4	24.3	29.8	34.2	< 0.001
Lipid profile
Mean LDL, mg/dL	118.2 ± 35.4	121.3 ± 36.2	123.8 ± 37.1	125.4 ± 37.8	< 0.001
Mean HDL, mg/dL	44.3 ± 13.2	43.1 ± 12.8	42.2 ± 12.5	41.4 ± 12.3	< 0.001
Mean triglycerides, mg/dL	178.4 ± 98.3	186.2 ± 102.4	192.8 ± 106.3	198.4 ± 109.2	< 0.001

BMI: Body mass index; HbA1c: Hemoglobin A1c; LDL: Low-density lipoprotein; HDL: High-density lipoprotein.

Table 7 Multivariable predictors of major adverse cardiovascular events in our hospital cohort

Predictor	Adjusted hazard ratios (95% confidence interval)	P value
Demographic factors
Age (per 10 years)	1.42 (1.35-1.49)	< 0.001
Male sex	1.34 (1.21-1.48)	< 0.001
Black race (vs White)	1.23 (1.09-1.39)	0.001
Traditional CV risk factors
Obesity (BMI ≥ 30)	2.34 (2.11-2.59)	< 0.001
Diabetes mellitus	2.12 (1.89-2.37)	< 0.001
Hypertension	1.78 (1.60-1.98)	< 0.001
Dyslipidemia	1.56 (1.41-1.73)	< 0.001
Current smoking	1.67 (1.51-1.85)	< 0.001
Psychiatric factors
Duration at our facility (per year)	1.03 (1.02-1.04)	< 0.001
Hospitalizations (per admission)	1.08 (1.05-1.11)	< 0.001
Negative symptom severity	1.12 (1.06-1.18)	< 0.001
Medication factors
Antipsychotic polypharmacy	1.67 (1.49-1.87)	< 0.001
High metabolic risk AP	1.89 (1.68-2.13)	< 0.001
CPZ equivalent dose (per 100 mg)	1.09 (1.05-1.13)	< 0.001

CV: Cardiovascular; BMI: Body mass index; AP: Antipsychotic; CPZ: Chlorpromazine.

Table 8 Subgroup analysis of obesity-associated cardiovascular risk in our hospital population

Subgroup	n	MACE events, n (%)	Obesity hazard ratios (95% confidence interval)	P interaction
Age group				0.012
18-35 years	2834	234 (8.3)	3.12 (2.56-3.80)
36-50 years	4123	756 (18.3)	2.45 (2.12-2.83)
51-65 years	3043	852 (28.0)	1.98 (1.71-2.29)
Sex				0.003
Male	5820	1123 (19.3)	2.12 (1.86-2.41)
Female	4180	719 (17.2)	2.78 (2.34-3.30)
Illness duration at our facility				0.045
< 5 years	3421	423 (12.4)	2.89 (2.43-3.44)
5-15 years	3876	734 (18.9)	2.34 (2.01-2.72)
> 15 years	2703	685 (25.3)	1.98 (1.68-2.33)
Antipsychotic risk				0.021
High risk	3890	823 (21.2)	2.67 (2.29-3.11)
Moderate risk	2987	543 (18.2)	2.23 (1.87-2.66)
Low risk	1857	287 (15.5)	1.89 (1.49-2.40)

MACE: Major adverse cardiovascular events.