This retrospective study was conducted among the hospitalized patients who were diagnosed with cerebrovascular diseases in the Third Affiliated Hospital of Soochow University. From January 2017 to January 2018, a total of 870 participants were recruited with the inclusion criteria: 1) who agreed to participate the present study with the informed form; 2) the cerebrovascular diseases were diagnosed according to computed tomography (CT) or magnetic resonance imaging (MRI) scans. Each patient underwent a face-to-face interview for a standard questionnaire and blood samples collection for biochemical measurements. For present analysis, the exclusive criteria were: 1) patients with subarachnoid hemorrhage, transient ischemic attack without progression to stroke or lacunar infarction (n=7); (2) missing information on lipid profiles, blood pressure and plasma glucose (n=4); (3) extreme value of body mass index (BMI) (n=3). Eventually, 856 participants were enrolled in present study.
The study protocol was approved by the Ethics Committee of the Third Affiliated Hospital of Soochow University. Each participants provided the written informed consent.
A face-to-face interview was performed through a standard questionnaire for the collection of information on sociodemographic characteristics, lifestyle and medical history. Current smokers and drinkers were defined as those who have smoked cigarettes and consumed alcohol in the past six months. Physical activity was divided into high physical activity or not, based on the International Physical Activity Questionnaire (IPAQ). Dietary habit was classified as omnivorous, vegetable activists, and meat activists, as well as the duration and frequency of consuming vegetables, fruits and dairy products were collected.
Anthropometric information of each participant including blood pressure, height and body weight was measured by trained personnel according to a standard protocol. Blood pressure was measured using an automated electric device (OMRON Model HEM-752 FUZZY, Omron Company, Dalian, China), on the non-dominant arm. Two blood pressure measurements were taken with 1-minute interval, the mean of two values were defined as the available blood pressure in the current analysis. BMI was calculated as weight in kilogram divided by squared height in meters.
After at least 10-hour fasting, blood samples of each participants were obtained for the measurements of fasting plasma glucose (FPG) and lipid profiles (triglyceride, TG; low-density lipoprotein cholesterol, LDL-c; high-density lipoprotein cholesterol, HDL-c; total cholesterol, TC), which were measured by an autoanalyzer (AU-5800 Chemistry System, Beckman, USA).
Obesity and metabolic phenotypes
Obesity phenotypes were defined as BMI ≥25kg/m2 and non-obesity as BMI<25kg/m2 based on the BMI cut-point among Asian population13, which had been verified among Chinese population recently14, 15.
According to Adult Treatment Panel III (ATP-III), the metabolic phenotypes were determined as: 1) elevated blood pressure: systolic blood pressure (SBP) ≥130mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg, and/or taking of antihypertensive drugs; 2) elevated blood glucose: FPG ≥5.6mmol/l, and/or taking of antidiabetic drugs; 3) high TG: TG ≥1.7mmol/l, and/or taking lipid-lowing medication; 4) low HDL-c: HDL-c <1.04mmol/l in men and <1.29mmol/l in women. Individuals with two or fewer of the previously mentioned items were considered as being in a metabolically healthy status.
Crossing the obese and metabolic phenotypes, we defined 1) metabolically healthy non-obesity (MHNO) as BMI <25 kg/m2 and metabolically healthy status, 2) metabolically healthy obesity (MHO) as BMI≥25kg/m2 and metabolically healthy status, 3) metabolically unhealthy non-obesity (MUNO) as BMI <25 kg/m2 and metabolically unhealthy status, 4) metabolically unhealthy obesity (MUO) as BMI≥25kg/m2 and metabolically unhealthy status.
Among the participants having a history of previous stroke, those with newly-onset stroke diagnosed by neurologists based on clinical symptoms, physical signs, and CT/MRI suggestions were considered as recurrent stroke.
The current analyses were conducted based on the combined obesity and metabolic phenotypes. Mean ± standard (SD) and median (interquartile range) were used as the normally distributed and skewed continuous variables. Numbers (proportions) were used as the categorical variables. One-way ANOVA for continuous variables and the Chi-square for categorical variables were performed for the comparisons among the four phenotypes; linear regression was used to analyze the trend across the four phenotypes.
Dependent on multivariate logistic regression analyses, odds ratios (ORs) and 95% confidence intervals (CIs) were presented as the risk of recurrent stroke across the variant BMI groups, ATP-III components, and metabolic phenotypes, as well as the four phenotypes across the obesity and metabolic status.
We calculated C statistics, net reclassification index (NRI), and integrated discrimination improvement (IDI) to evaluate the incremental prognostic values of individual BMI/metabolic status or the combined risk factors beyond conventional risk factors16.
We used SAS statistical software (version 9.3, Cary, NC) to perform all the statistical analyses, and considered two-tailed P values <0.05 were statistically significant.