Preclinical Atherosclerosis and MetS Increase CV Events
Preclinical Atherosclerosis and MetS Increase CV Events
Our study was performed on a population of 529 asymptomatic patients, aged between 25 and 87 years old (62 yrs ± 12.79) at baseline, divided in 257 male patients and 272 females, who were attending twenty years ago our "Centre for the Early Diagnosis of Preclinical and Multifocal Atherosclerosis and for the Cardiovascular Prevention", in Palermo, Italy. We identified 529 asymptomatic subjects at baseline from our registry of more than 9000 patients referred from 1985 to 1991 and in follow-up in our centre. From this registry we selected the population evaluated in the present study with MetS, according to the document of Scientific International Societies - International Diabetes Federation (IDF), National Heart, Lung, and Blood Institute (NHLBI), World Hearth Federation, International Atherosclerosis Society e American Heart Association (AHA) – published in 2009, which defined MetS as an alteration in 3 or more of the following 5 components: abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure (BP), and fasting plasma glucose. The following cut-off values were used to define alterations: waist circumference >102 cm for men and >88 cm for women for abdominal obesity, triglycerides ≥150 mg/dL (1.69 mmol/L), HDL-cholesterol <40 mg/dL (1.04 mmol/L) for men and < 50 mg/dL (1.29 mmol/L) for women, BP ≥ 130/≥85 mm Hg and fasting glucose ≥ 100 mg/dL. The choice of cutoff values for waist circumference was done according to the recent published consensus, taking into consideration the geographic distribution. The most common CV risk factors (lifestyle, dietary habits, smoking, family and personal history of CV disease) were investigated. Moreover we evaluated the anthropometric parameters (weight, height, and waist circumference) and the laboratory ones (fasting triglycerides, HDL-c, fasting glucose and fasting insulin), as well as blood pressure. Figure 1 shows the prevalence of the mean cardiovascular risk factors in the population evaluated.
(Enlarge Image)
Figure 1.
Prevalence of the cardiovascular risk factors in the study population.
Body mass index (BMI) has been calculated as weight in kilograms divided by the square of height in meters. Waist circumference was calculated as the average of 2 measurements taken after inspiration and expiration at the midpoint between the lowest rib and iliac crest. Blood pressure (BP) measurements were performed with participants in the seated position and after a quiet resting period of 5 minutes. BP was measured in both arms with a random-zero mercury sphygmomanometer; the BP values used in this study are the average of the measurements on both the right and left arms. Pulse pressure was computed as the difference between the systolic.
BP (SBP) and the diastolic BP (DBP). Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions were separated from fresh serum by combined ultracentrifugation and precipitation; triglycerides were measured enzymatically. Blood glucose was measured using a glucose dehydrogenase method after precipitation of proteins by trichloroacetic acid.
We excluded patients affected by cancer, inflammatory bowel disease and with other autoimmune disorders because these diseases were considered as confounding variables for their ability to power the atherosclerosis process.
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
Our research was carried out in compliance with the Helsinki Declaration and with international guidelines for the research on humans.
Ultrasound examination was performed in all patients at baseline, in order to investigate the presence of preclinical atherosclerosis. B-mode real-time ultrasound was used to evaluate the arterial wall thickness in the carotid arteries using a machine Toshiba 270 SS with a probe of 7.5 to 10.0 MHz. The power output, focus, depth of measurement, and gain were standardized by using the preset program incorporated within the software package of the ultrasound equipment. The IMT was defined as the distance between the echogenic line representing the intima- blood interface and the outer-echogenic line representing the adventitia junction. After freezing the image, the measurement was made with electronic calipers. Patients were examined in the supine position, and each carotid wall and segment was examined to identify the thickest intimal-medial site. Three segments were identified and measured in anterior and posterior planes on each side: the distal 1 cm of the common carotid proximal to the bifurcation, the bifurcation itself, and the proximal 1 cm of the internal carotid artery. At each of these sites, we have determined the IMT, automatically measured, and detected any possible plaque. We primarily used the maximum carotid IMT value, which was determined as the mean of the maximum IMT of near- and far-wall measurements of both the left and right side arteries for each of the 3 arterial segments. If data on one of the walls or one of the sides were missing, maximum thickness of the available wall and side was used. The percentage of missing data was ≈ 35% (probably because of technical difficulties in the evaluation). Ultrasound examination was performed by one investigator, in blind and with no possibility of reproducing the IMT measurement. Carotid ultrasonography was performed by one sonographer to limit the risk of a large interobserver variability. However, for methodological correctness, the intraobserver agreement for sonographic measurement was calculated with a 4.1% to 5.0% coefficient of variation for repeated scans.
Cardiovascular endpoints were investigated in a 20-years follow-up: acute myocardial infarction (AMI), angina pectoris, transient ischemic attack (TIA), ischemic stroke, abdominal aortic aneurysm (AAA), thromboendarterectomy (TEA) and cardiovascular death. Not fatal events were investigated through clinical controls during the follow-up in hospital. Fatal events were ascertained through the interrogation of family members or death certificates.
Descriptive statistics were presented as percentages for categorical variables and as mean values ± standard deviation (SD) for continuous data. Differences between groups were compared by the Chi-square test for categorical variables. In addition, free-events survival was tested by Kaplan-Meyer function and log-rank test. A p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the Med Calc Program.
Methods
Patients
Our study was performed on a population of 529 asymptomatic patients, aged between 25 and 87 years old (62 yrs ± 12.79) at baseline, divided in 257 male patients and 272 females, who were attending twenty years ago our "Centre for the Early Diagnosis of Preclinical and Multifocal Atherosclerosis and for the Cardiovascular Prevention", in Palermo, Italy. We identified 529 asymptomatic subjects at baseline from our registry of more than 9000 patients referred from 1985 to 1991 and in follow-up in our centre. From this registry we selected the population evaluated in the present study with MetS, according to the document of Scientific International Societies - International Diabetes Federation (IDF), National Heart, Lung, and Blood Institute (NHLBI), World Hearth Federation, International Atherosclerosis Society e American Heart Association (AHA) – published in 2009, which defined MetS as an alteration in 3 or more of the following 5 components: abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure (BP), and fasting plasma glucose. The following cut-off values were used to define alterations: waist circumference >102 cm for men and >88 cm for women for abdominal obesity, triglycerides ≥150 mg/dL (1.69 mmol/L), HDL-cholesterol <40 mg/dL (1.04 mmol/L) for men and < 50 mg/dL (1.29 mmol/L) for women, BP ≥ 130/≥85 mm Hg and fasting glucose ≥ 100 mg/dL. The choice of cutoff values for waist circumference was done according to the recent published consensus, taking into consideration the geographic distribution. The most common CV risk factors (lifestyle, dietary habits, smoking, family and personal history of CV disease) were investigated. Moreover we evaluated the anthropometric parameters (weight, height, and waist circumference) and the laboratory ones (fasting triglycerides, HDL-c, fasting glucose and fasting insulin), as well as blood pressure. Figure 1 shows the prevalence of the mean cardiovascular risk factors in the population evaluated.
(Enlarge Image)
Figure 1.
Prevalence of the cardiovascular risk factors in the study population.
Body mass index (BMI) has been calculated as weight in kilograms divided by the square of height in meters. Waist circumference was calculated as the average of 2 measurements taken after inspiration and expiration at the midpoint between the lowest rib and iliac crest. Blood pressure (BP) measurements were performed with participants in the seated position and after a quiet resting period of 5 minutes. BP was measured in both arms with a random-zero mercury sphygmomanometer; the BP values used in this study are the average of the measurements on both the right and left arms. Pulse pressure was computed as the difference between the systolic.
BP (SBP) and the diastolic BP (DBP). Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) fractions were separated from fresh serum by combined ultracentrifugation and precipitation; triglycerides were measured enzymatically. Blood glucose was measured using a glucose dehydrogenase method after precipitation of proteins by trichloroacetic acid.
We excluded patients affected by cancer, inflammatory bowel disease and with other autoimmune disorders because these diseases were considered as confounding variables for their ability to power the atherosclerosis process.
Patient's Consent
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
Our research was carried out in compliance with the Helsinki Declaration and with international guidelines for the research on humans.
Echo Color Doppler Examination of Carotid Arteries
Ultrasound examination was performed in all patients at baseline, in order to investigate the presence of preclinical atherosclerosis. B-mode real-time ultrasound was used to evaluate the arterial wall thickness in the carotid arteries using a machine Toshiba 270 SS with a probe of 7.5 to 10.0 MHz. The power output, focus, depth of measurement, and gain were standardized by using the preset program incorporated within the software package of the ultrasound equipment. The IMT was defined as the distance between the echogenic line representing the intima- blood interface and the outer-echogenic line representing the adventitia junction. After freezing the image, the measurement was made with electronic calipers. Patients were examined in the supine position, and each carotid wall and segment was examined to identify the thickest intimal-medial site. Three segments were identified and measured in anterior and posterior planes on each side: the distal 1 cm of the common carotid proximal to the bifurcation, the bifurcation itself, and the proximal 1 cm of the internal carotid artery. At each of these sites, we have determined the IMT, automatically measured, and detected any possible plaque. We primarily used the maximum carotid IMT value, which was determined as the mean of the maximum IMT of near- and far-wall measurements of both the left and right side arteries for each of the 3 arterial segments. If data on one of the walls or one of the sides were missing, maximum thickness of the available wall and side was used. The percentage of missing data was ≈ 35% (probably because of technical difficulties in the evaluation). Ultrasound examination was performed by one investigator, in blind and with no possibility of reproducing the IMT measurement. Carotid ultrasonography was performed by one sonographer to limit the risk of a large interobserver variability. However, for methodological correctness, the intraobserver agreement for sonographic measurement was calculated with a 4.1% to 5.0% coefficient of variation for repeated scans.
Follow-up
Cardiovascular endpoints were investigated in a 20-years follow-up: acute myocardial infarction (AMI), angina pectoris, transient ischemic attack (TIA), ischemic stroke, abdominal aortic aneurysm (AAA), thromboendarterectomy (TEA) and cardiovascular death. Not fatal events were investigated through clinical controls during the follow-up in hospital. Fatal events were ascertained through the interrogation of family members or death certificates.
Statistical Analysis
Descriptive statistics were presented as percentages for categorical variables and as mean values ± standard deviation (SD) for continuous data. Differences between groups were compared by the Chi-square test for categorical variables. In addition, free-events survival was tested by Kaplan-Meyer function and log-rank test. A p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the Med Calc Program.
