Impact of multiple cardiovascular risk factors on femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa Heart Study)

Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification.     

Framingham risk score is related to carotid artery intima-media thickness in both white and black young adults: the Bogalusa Heart Study

The Framingham risk score (FRS), developed in a white cohort aged 30-74 years, is increasingly used in the early risk identification for coronary artery disease (CAD). This study examines the relationship between FRS and carotid artery intima-media thickness (IMT), a surrogate marker of coronary atherosclerosis, in black and white individuals aged 20-37 years. Five hundred seventeen young adults (aged 20-37 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study had carotid artery ultrasonography. Age, gender, systolic blood pressure, total cholesterol to HDL cholesterol ratio, cigarette smoking habit, type 2 diabetes, and left ventricular hypertrophy (LVH) were used to calculate FRS. Results indicated a significant, positive linear relationship between tertiles of FRS and IMT of the common, bulb, and internal carotid segments in blacks and whites alike. In a multivariate analysis including FRS, race, BMI, parental history of CAD, stroke, type 2 diabetes, or hypertension, logtriglycerides, loginsulin, alcohol consumption (ml/week), and regular physical activity, the FRS was independently associated with all three carotid segments. Further, the FRS as a main predictor variable explained relatively more of the variance in the IMT of the carotid bulb (9%) than in the common (5%) or internal (3%) carotid segments. These results support the use of FRS in both white and black young adults and underscore the importance of prevention and control of multiple risk factors in youth.     

Cardiovascular risk profile of asymptomatic healthy young adults with increased femoral artery intima-media thickness: The Bogalusa Heart Study

BACKGROUND: Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. This study examined the cardiovascular disease risk profile of asymptomatic young adults with increased femoral artery IMT. METHODS: Femoral artery IMT was measured by B-mode ultrasonography in 1080 black and white subjects (aged 24-43 years; 71% white, 43% male) enrolled in the Bogalusa Heart Study. Individuals in the top (n=54) versus bottom fifth (n=54) percentiles distribution of femoral IMT were compared for traditional cardiovascular risk factors profile. Univariate analysis compared the two groups, t-tests and chi tests were performed. RESULTS: The top and bottom fifth percentiles of IMT differed with respect to age (P<0.001), systolic blood pressure (P<0.05), diastolic blood pressure (P<0.05), total cholesterol (P<0.01), low-density lipoprotein (LDL) cholesterol (P<0.001), non-high-density lipoprotein (HDL) cholesterol (P<0.01) and smoking status (P<0.01). In terms of prevalence of clinically defined traditional risk factors, individuals at the top versus bottom fifth percentile of IMT distribution had significantly higher prevalence of high LDL cholesterol (>OR=130 mg/dL), non-HDL cholesterol (>OR=160 mg/dL), and cigarette smoking. The odds ratio for individuals with three or more risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (P=0.01). CONCLUSION: The observed adverse effect of cardiovascular risk factors on IMT of femoral artery, a surrogate measure of coronary and peripheral atherosclerosis, in asymptomatic young individuals underscores the need for risk factors profiling in early life. These observations have important implications in preventive medicine.     

Gender divergence on the impact of multiple cardiovascular risk factors on the femoral artery intima-media thickness in asymptomatic young adults: the Bogalusa Heart Study

IntroductionGender divergence on the impact of multiple cardiovascular risk factors on the femoral artery intima-media thickness (IMT) has not been studied in a biracial (black-white) community-based asymptomatic young adults.MethodsFemoral IMT was measured by B-mode ultrasonography in 1080 individuals (age, 24–43 years; 71% white; 43% men) enrolled in the Bogalusa Heart Study.ResultsFemoral IMT showed a gender difference (men > women; P = 0.001), but no racial difference. In a multivariate model, age, cigarette smoking, systolic blood pressure and total cholesterol to high-density lipoprotein cholesterol ratio related independently, in that order, to IMT in women, and age and low-density lipoprotein cholesterol in men. In women, mean IMT increased with increasing number of risk factors defined as values above the age-, race- and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol to high-density lipoprotein cholesterol ratio and insulin along with positive smoking status (P for trend = 0.001), with respective mean IMT (mm) values of 0.61, 0.65, 0.72 and 0.77, for 0, 1 to 2, 3 and 4 to 5 risk factors. There was no such significant trend in men.ConclusionsAlthough men versus women had thicker IMT, the observed increasing trend of femoral IMT with increasing number of risk factors in asymptomatic young women suggests that women may be relatively more susceptible to the burden of multiple risk factors.     

Impact of multiple coronary risk factors on the intima-media thickness of different segments of carotid artery in healthy young adults (The Bogalusa Heart Study)

Although risk factors for coronary artery disease are also associated with increased carotid artery intima-media thickness (IMT) as measured by B-mode ultrasonography in middle-aged and older persons, information on the impact of multiple risk factors on the IMT of different segments of the carotid artery in young adults is limited. This relation was examined in a sample of 518 black and white subjects (mean age 32 years; 71% white, 39% male) enrolled in the Bogalusa Heart Study. IMT was thicker and more skewed in the bulb compared with other carotid segments. Race differences (blacks more than whites) were noted for the common carotid (p <0.001) and carotid bulb (bifurcation) IMT (women only, p <0.001). Men had a greater IMT in the common carotid (p <0.05), internal carotid (p <0.05), and carotid bulb (whites only, p <0.001). In a multivariate analysis, systolic blood pressure, race, age, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol weree entered into a model in that order and accounted for the 16.7% variance in the common carotid IMT; age, systolic blood pressure, HDL cholesterol, LDL cholesterol, race, and insulin levels explained the 19.4% variance in the carotid bulb IMT. Gender and body mass index (BMI) accounted for the 4.7% variance in the internal carotid IMT. Increases in IMT with increasing number of risk factors (cigarette smoking, higher total cholesterol to HDL cholesterol ratio, higher systolic blood pressure, greater waist circumference, and higher insulin level) were noted for the common carotid and carotid bulb segments (p for trend <0.001 for both). The observed deleterious trend of increasing IMT at different carotid segments with increasing number of risk factors in free-living, asymptomatic young subjects underscores the importance of profiling multiple risk factors early in life. Ultrasonography of carotid arteries, especially at the bifurcation, may be helpful along with measurements of risk factors for evaluation of asymptomatic atherosclerotic disease.     

Correlation between the intima-media thickness and Framingham risk score in patients with sleep apnea syndrome

Background

In the present study, we want to demonstrate the correlation between obstructive sleep apnea syndrome (OSAS) whose independent effect on carotid artery intima-media thickness (IMT) was demonstrated, with Framingham risk score (FRS) showing the overall cardiovascular risk.

Methods

IMT of the carotid artery was measured with ultrasonography and 10-year risk of coronary heart disease (CHD) was defined with FRS in 90 consecutive patients referred to our sleep clinic and who underwent polysomnography (PSG), with vascular risk factors and without a clinical atherosclerotic disease.

Results

IMT and FRS were found to be statistically significantly increased in the severe OSAS group compared to the other two groups. Carotid IMT was found to be significantly positively correlated with, apnea-hypopnea index (AHI), oxygen desaturation index (ODI) and time duration with oxygen saturation (SpO₂) <90%, and negatively correlated with minimum oxygen saturation at sleep (minimum SpO₂) and mean SpO₂. In control and mild OSAS group IMT and FRS have significantly positive correlation (r: 0.501, P: 0.027; r: 0.625, P<0.001), while in severe OSAS group no significant correlation was detected between IMT and FRS (r: 0.321, P: 0.06). In the regression analysis AHI and ODI were found to be an independent predictor of carotid IMT. ODI was found to have an independent effect on the progression of atherosclerosis.

Conclusions

Increased carotid IMT in severe OSAS group could not be explained with the classical risk factors. In this respect, FRS might be insufficient to determine correctly the cardiovascular risk and protection strategies against the disease in OSAS patients.KEYWORDS : Carotid artery, Framingham risk score (FRS), sleep apnea     

Metabolic syndrome is associated with coronary artery calcium in asymptomatic white Brazilian men considered low-risk by Framingham risk score

The authors investigated whether the metabolic syndrome is associated with coronary artery calcium (CAC) independently of 10-year coronary heart disease risk assessment by Framingham risk scores (FRS) in asymptomatic white Brazilian men. In a group of 458 men (mean age 46+/-7 years), the 10-year coronary heart disease risk was 9%+/-8%, and the metabolic syndrome and CAC were present in 24% and 41% of the participants, respectively. Compared with those classified as low risk (<10% FRS; n=256), men with FRS of 10% or more had an odds ratio of 4.57 (95% confidence interval, 3.08-6.82; P<.0001) for the presence of any CAC. The prevalence of CAC increased monotonically with the increasing number of metabolic syndrome components (none=29%, 1 or 2=44%, and >or=3=51%, P=.002 for trend). The presence of the metabolic syndrome was associated with an increased risk of CAC: odds ratio, 1.94 (95% CI, 1.05-3.61); however, this finding was significant only in those individuals classified as low risk (FRS <10%). In conclusion, metabolic syndrome is associated with subclinical atherosclerosis in Brazilian participants considered at low risk according to FRS.     

Increased carotid intima-media thickness is associated with higher SYNTAX score

The main purpose of this study was to investigate the relation between carotid intima-media thickness (CIMT) and coronary artery disease (CAD) complexity. Consecutive patients (n = 360) with CAD confirmed by coronary angiography were enrolled. Mean CIMT and the overall SYNTAX score (SXscore) were 0.87 ± 0.12 mm and 15 ± 9, respectively. In univariate analysis, there was a significant correlation between the overall SXscore and CIMT (r = .42, P < .001), age (r = .23, P < .001), hypertension (r = .27, P = 0.001), diabetes (r = 0.11, P = 0.02), smoking (r = .24, P = .01), dyslipidemia (r = .2, P = 0.03), and β-blocker use (r = .19, P < .001). In multivariate analysis, CIMT (β = .34, P < .001) and age (β = .11, P < .019) were independently associated with SXscore. We have demonstrated a significant relation between CIMT and SXscore. Although this study is correlative and no causative conclusions can be drawn, our findings suggest that increased CIMT could reflect complex coronary artery lesions.     

Carotid artery intima-media thickness is associated with coronary artery disease

OBJECTIVE: The intima-media thickness (IMT) of the carotid artery is dependent on the risk factor load during life and correlates well with the degree of atherosclerosis, also in other vascular beds. METHODS: We reviewed our database of IMT measurements, from January 2002 to February 2007. We compared the mean IMT values of patients without a history of coronary artery disease (group 1) with those with a history of coronary artery disease (group 2). For both groups we divided the results of measurements according to age. We compared the IMT between both groups and looked for a correlation with increasing age. The IMT was measured with high-resolution echography at the posterior wall of the common carotid artery, using an automated edge-tracking method. RESULTS: The database contained 598 IMT measurements in group 1 and 672 in group 2. In both groups we observed a significant increase in IMT with increasing age. Within a certain age group, a significant difference in IMT between group 1 and 2 occurred at an age of 40 years or above (age 40-65: IMT 645.54 versus 671.71 microm, respectively, P = 0.04, and age > 65 years: IMT 715.2 versus 772.91 microm, respectively, P = 0.01). CONCLUSIONS: IMT increases with age and is higher in patients with a history of vascular disease. This difference is significant in patients of 40 years or older. This finding supports the recommendations of the prevention conference of the American Heart Association, that carefully performed IMT measurement can add incremental information to traditional risk factor assessment in asymptomatic individuals above the age of 45 years.     

Association of Pathobiologic Determinants of Atherosclerosis in Youth risk score and 15-year change in risk score with carotid artery intima-media thickness in young adults (from the Cardiovascular Risk in Young Finns Study)

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study of autopsy findings in subjects 15 to 34 years of age developed a risk score using coronary heart disease risk factors (gender, age, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia) to estimate the probability of advanced atherosclerotic lesions in the coronary arteries. The Cardiovascular Risk in Young Finns Study measured coronary heart disease risk factors in a population-based cohort in 1986 and 2001 and measured carotid artery intima-media thickness (IMT) with ultrasonography in 2001. We computed the PDAY risk score from risk factors measured in 1,279 subjects who were 12 to 24 years of age in 1986 and 27 to 39 years of age in 2001. The PDAY risk score early in life (i.e., 1986) and the change in risk score in the following 15 years (i.e., 1986 through 2001) were independent predictors of carotid artery intima-media thickness; the multiplicative effect of 1 point in the 1986 risk score was 1.008 (95% confidence interval 1.005 to 1.012) and the multiplicative effect of a 1-point increase between the 1986 and 2001 risk scores was 1.003 (95% confidence interval 1.001 to 1.006; multiplicative effect of 0.997 for a 1-point decrease). In conclusion, the change in risk score over time (decrease or increase) during adolescence and young adulthood, as well as the risk score early in life, are important predictors of atherosclerosis.     

Racial (black-white) divergence in the association between adiponectin and arterial stiffness in asymptomatic young adults: the Bogalusa heart study

BACKGROUND: Adiponectin, an adipocytokine with beneficial biological functions relevant to cardiovascular (CV) diseases, and arterial stiffness, an indicator of vascular function, are considered to be important correlates of CV disease risk. Although racial (black-white) divergences in adiponectin and arterial stiffness are known, information is scant regarding the association between these two parameters among asymptomatic young adults within each race. METHODS: As part of the Bogalusa Heart Study, arterial stiffness was examined noninvasively in terms of aorta-femoral pulse wave velocity (af-PWV) in 991 black and white nondiabetic subjects (72% white, 43% male) aged 24-44 years. RESULTS: In a multivariate regression model by race that included adiponectin, age, sex, waist circumference, mean arterial pressure, heart rate, homeostasis model assessment of insulin resistance, low- and high-density lipoprotein cholesterols, triglycerides, and cigarette smoking, the significant predictors of af-PWV, in the order of entry, were: mean arterial pressure, age, smoking, and heart rate in both races, followed by adiponectin (inverse relation) in blacks. Further, after adjusting for mean arterial pressure, age, smoking, and heart rate, the odds ratio of finding excess af-PWV (top decile vs. the rest) in individuals with low adiponectin levels (bottom quartile vs. the rest) was significantly higher in blacks (OR: 2.5; 95% CI: 1.1-5.5), but not in whites (OR: 0.9; 95% CI: 0.5-1.9). CONCLUSIONS: These findings suggest that the status of hypoadiponectinemia is an independent correlate of excess arterial stiffness in asymptomatic young black adults.     

A low high density lipoprotein (HDL) level is associated with carotid artery intima-media thickness in asymptomatic members of low HDL families

Low serum high-density lipoprotein cholesterol (HDL-C) is a strong predictor of coronary heart disease (CHD). The aim of the present study was to evaluate the metabolic parameters predicting the atherosclerotic changes in asymptomatic members of low HDL-C families. We performed carotid B-mode ultrasonography with intima-media thickness (IMT) measurement for 89 asymptomatic members of Finnish low HDL-C families. The family members were categorized as affected or unaffected according to the 10th age-gender specific HDL-C percentile. In the affected group, the most marked decrease of HDL subclasses was observed for HDL2-C when compared with the unaffected (109% difference). In the partial correlation analyses, age and gender showed significant correlations with the mean IMT (for age, r=0.880, P<0.001, and for gender, r=-0.361, P=0.018). Importantly, HDL-C and HDL2-C were significantly inversely related to the mean carotid IMT, also after correction for age (for HDL-C, r=-0.186, P=0.043, for HDL2-C, r=-0.208, P=0.029, when adjusted for age). The correlation for HDL-C was significant also when adjusted for gender. In conclusion, low HDL-C is associated with increased carotid artery IMT in asymptomatic members of low HDL-C families.     

Usefulness of the Framingham risk score and body mass index to predict early coronary artery calcium in young adults (Muscatine Study)

The value of a coronary artery disease prediction algorithm, the Framingham risk score (score), for detecting coronary artery calcium (CAC) was examined in 385 men and 472 women, aged 29 to 43 years. Scores were compared in subjects with and without CAC and were also used to predict presence of CAC. Receiver-operating characteristic curves were computed to compare different prediction models. The score model was compared with age only, natural logarithm of body mass index (lnBMI) only, and score plus lnBMI models. CAC was detected in 30% of men and 16% of women. The mean score was significantly higher in men and women with CAC. For every 2-point increase in the score, the odds of CAC increased by 30% in women and 20% in men. Significant associations between CAC status and risk factors were observed for age in women, and high- density lipoprotein cholesterol and blood pressure in men and women. The area under the receiver-operating characteristic curve for the score was 0.67 and 0.57 for women and men, respectively. When lnBMI was added to the score model, the area increased to 0.76 in women (lnBMI p <0.0001, score p <0.005). For men, the area increased from 0.57 to 0.67, and the score was no longer significant (p >0.60) in the model with lnBMI (p <0.0001). Score predicts CAC in asymptomatic young adults. Inclusion of lnBMI in the score model adds significantly to the prediction of CAC in women and men. The lnBMI model has a greater predictive value than the score in this young population.     

Habitual aerobic exercise is associated with smaller femoral artery intima-media thickness with age in healthy men and women.

BACKGROUND: Femoral artery intima-media thickness (IMT), an independent predictor of atherosclerotic disease risk, increases with age in sedentary adults. It is not known whether regular aerobic exercise modulates femoral IMT with ageing. METHODS AND RESULTS: Study 1: Femoral IMT was measured in 173 sedentary, moderately active, and endurance-trained young (20-39 years), middle-aged (40-59 years) and older (60-79 years) men. IMT increased with age in all activity groups (P<0.001). However, IMT was 20-27% smaller in age-matched, endurance-trained compared with sedentary men (P<0.001), and the age-associated increase in IMT was 33% smaller in endurance-trained compared with sedentary men (+0.32 versus +0.45 mm). There was a trend for the IMT to be smaller in moderately active compared with sedentary older men, and the age-associated increase in IMT was 37% smaller in moderately active than sedentary men (+0.28 mm). Study 2: Among 74 premenopausal and postmenopausal sedentary or endurance-trained women, IMT was higher (P<0.001) in postmenopausal compared with premenopausal women regardless of activity status. However, IMT was 15% smaller in endurance-trained compared with sedentary postmenopausal women (P<0.001), and the premenopausal to postmenopausal difference in IMT was approximately 45% smaller in endurance-trained compared with sedentary women (+0.13 versus +0.23 mm). CONCLUSIONS: Femoral IMT increases with age even in habitually exercising adults. However, the age-associated increase and absolute level of IMT are smaller in middle-aged and older adults who perform regular aerobic-endurance exercise, and may contribute to their lower incidence of atherosclerotic disease.     

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative

Aims/hypothesis

The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes.

Methods

We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added.

Results

During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI ?1.8, 3.8). There were no differences in the results between men and women.

Conclusions/interpretation

There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.     

Influence of nitric oxide synthase gene polymorphism (G894T) on carotid artery intima-media thickness in adults: the Bogalusa Heart Study

Nitric oxide generated by the vascular endothelial nitric oxide synthase (eNOS) plays an important role in the regulation of vascular structure/function and blood pressure. However, information is scant regarding the influence of G894T polymorphism of the eNOS gene on arterial wall thickness in asymptomatic young adults. This aspect was examined for G894T polymorphism in 661 White and Black subjects, aged 25 to 43 years (73.2% White; 39.5% male). Arterial vascular changes were assessed by common carotid intima-media thickness (IMT) using B-mode ultrasonography. The variant T allele frequency of G894T was significantly higher in Whites compared with Blacks (0.339 vs. 0.102; P < .0001). In bivariate analysis, adjusted for gender, age, mean arterial blood pressure, and/or race, carotid IMT was marginally lower in carriers vs. non-carriers of T allele in Whites (P = .07), but significantly lower for the total number of subjects (P = .04). In multivariable regression analysis, adjusted for gender, age, mean arterial pressure, body mass index (BMI), low-density lipoprotein cholesterol, triglycerides/high-density lipoprotein cholesterol ratio, homeostasis model assessment of insulin resistance, smoking, and race (in the total sample), the variant allele was independently associated with lower carotid IMT in both the White subjects (P = .04), and total sample (P = .03). These results suggest that the allelic variation of G894T polymorphism of the eNOS gene beneficially influences vascular changes as measured by carotid IMT in asymptomatic young adults.