Methods

The GHS was designed as a community-based, prospective, observational, single-center cohort study in the Rhine-Main region of western Germany. The study design and inclusion and exclusion criteria have been published previously. The sample was stratified 1:1 for gender and residence and in equal strata for decades of age. Subjects aged 35 to 74 years were enrolled, and written informed consent was obtained from all participants. The study protocol and the sampling design were approved by the local ethics committee and by the local and federal data safety commissioners. We investigated cross-sectional data of the first 5,000 subjects enrolled in the GHS from April 2007 to October 2008. The overall response rate of the subjects invited was 60.4% for this cross-sectional analysis. Each study participant was instructed in detail concerning the study in all aspects and supplied written informed consent before participation.

Arterial hypertension was defined as systolic blood pressure >140 mm Hg and diastolic blood pressure >90 mm Hg obtained as the mean of 3 separate measurements. Subjects taking medications for arterial hypertension were also classified as having arterial hypertension. Smokers were categorized as ever smokers when they had histories of constant smoking once during their lifetimes or as never smokers when no active smoking was present until inclusion into the study. For analysis, patients were divided into current or ex-smokers. Patients with diabetes mellitus included all those treated with oral blood glucose–lowering therapy or with substitution of insulin. Patients with diagnoses of dyslipidemia performed by general practitioners or with ratios of low-density lipoprotein (LDL) to high-density lipoprotein (HDL) >3.5 were classified as having dyslipidemia. Positive family history of myocardial infarction was defined as a first-degree relative with myocardial infarction at age <60 years for men and <65 years for women. A body mass index (BMI) >30 kg/m ² was defined to be pathologic according to published research.

For the determination of normal IMT values, patients with dyslipidemia, BMIs >30 kg/m ² , arterial hypertension, diabetes mellitus, smoking, family histories of myocardial infarction, known coronary artery disease, or heart failure were excluded, and the remaining 1,025 subjects (21.3%) were defined as healthy volunteers without cardiovascular risk factors.

IMT was assessed using an iE33 ultrasound system (Philips Medical Systems, Best, The Netherlands) using an 11- to 3-MHz linear-array transducer. Evaluation was performed using an automatic computerized system (QLAB; Philips Medical Systems), and triggering was performed according to the Q wave on electrocardiography to enable measurement in complete relaxation of the ventricle. Mean IMT was recorded 1 cm before the carotid bulb over a length of 1 cm at the far wall of both CCAs. Only parts of the CCA without plaques were included in the IMT analysis. Plaques were defined as protrusions into the lumen of ≥1.5 mm, and screening for plaques was performed for common, internal, and external carotid arteries according to previous investigations. After quality control of each ultrasound examination, 4,814 of 5,000 subjects (96.3%) were included in the final analysis.

Blood samples were drawn after an overnight fasting period, and glucose, LDL cholesterol, and HDL cholesterol were determined with standardized assays (Abbott Diagnostics). C-reactive protein (CRP) was determined by latex particle–enhanced immunoassay (Abbott Laboratories, Abbott Park, Illinois) with a variable range by substituting the 320 mg/L calibrator from the standard CRP calibrator set (5 to 320 mg/L) with a 2.5 mg/L or a 480 mg/L calibrator for ultrasensitive and wide-range CRP testing. The limit of detection was ≤0.1 mg/L for the ultrasensitive calibrator and ≤0.2 mg/L for the wide-range calibrator. The immunoassay was performed on an Architect analyzer (Abbott Laboratories). Fibrinogen was determined by derived method.

All analyses were stratified by gender. Of the descriptive analyses for baseline cardiovascular risk factors and clinical variables, continuous skewed variables are expressed as medians and 25th and 75th percentiles and symmetric variables as mean ± SD. Nomograms were constructed using quantile regression. The relations of categorical clinical variables to IMT were examined, calculating medians and quartiles of IMT for all categories of the dichotomous variables and comparing IMT levels between the categories using Mann-Whitney U tests. For this analysis, the dichotomized risk factors were used. Multiple quantile (median) regression was performed to elucidate which factors influence IMT at a statistically significant level. Multiple logistic regressions were used to explore which variables are associated with the presence of any carotid plaque. The same set of candidate variables using subject matter knowledge together with hierarchical clustering to assess and avoid collinearity. Given the exploratory nature of this study, hypothesis testing was done for descriptive purposes, and therefore no adjusting for multiple testing was performed. Analyses were performed using R version 2.10.0 (R Development Core Team, Vienna, Austria).

Results

Comparing the overall cohort with regard to gender differences, men were slightly older than women. The prevalence of most cardiovascular risk factors was higher in men than in women ( Table 1 ). Men had significantly higher systolic and diastolic blood pressures, higher fasting glucose, and lower HDL cholesterol levels. In addition, men more often had histories of coronary artery disease, while the overall prevalence of cardiovascular diseases was quite low in this population. Women had higher CRP and fibrinogen levels compared to men.

For the total GHS cohort, median CCA IMT applying the average from both sides was 0.62 mm (25th percentile 0.55, 75th percentile 0.70) in women and 0.65 mm (25th percentile 0.57, 75th percentile 0.75) in men (p <0.0001). The relation between IMT and age for each gender is visualized in a nomogram in Figure 1 . We found a significant correlation between IMT and BMI for men and women (Spearman’s coefficient men 0.17, p <0.0001; Spearman’s coefficient for women 0.25, p <0.0001). IMT values are shown separately for participants with BMIs >30 and <30 kg/m ² in Figure 1 . IMT was higher according to older age, and the gender difference persisted for all age groups.

Nomograms for CCA IMT according to gender and age for the total GHS cohort (A) (n = 4,814; comparison of participants with BMIs ≤30 or >30 kg/m ² ) and for the no-risk population (B) (n = 1,025; participants with BMIs >30 kg/m ² are excluded).

Any carotid plaque could be found in 30.7% of women and in 44.7% of men. Comparing different age decades, carotid plaques could be detected significantly more often in men than in women ( Figure 2 ). For both genders, the percentage of subjects with carotid plaques increased with advanced age, and 75.6% of the men and 57.7% of the women in the oldest age group (65 to 74 years) had any carotid plaque.

Prevalence of carotid plaques according to gender and age decades for the total GHS cohort (n = 4,814).

CCA IMT was significantly higher in subjects with a given risk factor compared to those without ( Table 2 ). Results were similar with regard to the presence of carotid plaques. Carotid plaques were more frequently detected in subjects with cardiovascular risk factors compared to those without cardiovascular risk factors.

To identify predictors of early carotid atherosclerosis, multivariate analyses were performed. In Table 3 the results of quantile regression are listed. Age, low HDL cholesterol, arterial hypertension, and smoking were positively correlated with higher IMT in men and women. High LDL cholesterol and diabetes were positively associated with higher IMT in men but not in women. Table 4 lists multiple logistic regression analysis for predictors of carotid plaques. Although age, arterial hypertension, HDL cholesterol, and smoking were significantly associated with carotid plaque in both genders; diabetes mellitus was significant only in men, and elevated LDL cholesterol was significant only in women. In men, low BMI was a predictor of plaques, but in the univariate analysis ( Table 2 ), BMI >30 kg/m ² was associated with a higher prevalence of plaques.

Table 3

Multiple quantile regression to indentify predictors of increased intima media thickness

Variable	Men (n = 2,433)			Women (n = 2,381)
	Coefficient	Coefficient for 1-SD Increase	p Value	Coefficient	Coefficient for 1-SD Increase	p Value
Age	0.0062	0.0680	<0.0001	0.0058	0.0640	<0.0001
CRP ⁎	0.0026	0.0024	0.32	−0.0007	−0.0007	0.77
LDL cholesterol	0.0004	0.0120	<0.0001	0.0001	0.0024	0.31
HDL cholesterol	−0.0007	−0.0090	0.0004	−0.0004	−0.0054	0.01
BMI	0.0010	0.0040	0.16	0.0010	0.0051	0.03
Diabetes mellitus	0.0380		0.0003	0.0230		0.08
Arterial hypertension	0.0200		0.0004	0.0280		<0.0001
Ever smoker	0.0220		<0.0001	0.0095		0.02
R 1	0.212			0.256

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

1. Comparison of Outcome of Recurrent Versus First ST-Segment Elevation Myocardial Infarction (from National Israel Surveys 1998 to 2006)
2. Outcomes After Unrestricted Use of Everolimus-Eluting Stent Compared to Paclitaxel- and Sirolimus-Eluting Stents
3. Usefulness of Coronary Pressure Measurement for Functional Evaluation of Drug-Eluting Stent Restenosis
4. Current Status of Aggressive Blood Glucose and Blood Pressure Control in Diabetic Hypertensive Subjects

Stay updated, free articles. Join our Telegram channel

Join