High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are strong predictors of atherosclerosis. Statin-induced changes in the ratio of LDL-C to HDL-C (LDL-C/HDL-C) predicted atherosclerosis progression better than LDL-C or HDL-C alone. However, the best predictor of subclinical atherosclerosis remains unknown. Our objective was to investigate this issue by measuring changes in carotid intima-media thickness (IMT). A total of 1,920 subjects received health examinations in 1999, and were followed up in 2007. Changes in IMT (follow-up IMT/baseline IMT × 100) were measured by ultrasonography. Our results showed that changes in IMT after eight years were significantly related to HDL-C (inversely, P < 0.05) and to LDL-C/HDL-C ratio (P < 0.05). When the LDL-C/HDL-C ratios were divided into quartiles, analysis of covariance showed that increases in the ratio were related to IMT progression (P < 0.05). This prospective study demonstrated the LDL-C/HDL-C ratio is a better predictor of IMT progression than HDL-C or LDL-C alone.
Endothelial function and carotid intima media thickness (cIMT) were investigated in a cohort of 54 healthy adults without known cardiovascular disease.
Pulse wave amplitude was determined with peripheral arterial tonometry (PAT) to obtain the reactive hyperemia (RH)-PAT ratio. Ultrasound was used to determine cIMT.
cIMT and RH-PAT were significantly associated (rho = −0.35, P = 0.02) in univariate analysis. RH-PAT was significantly associated with age, triglycerides, fasting glucose, HDL, WHR, waist circumference and VAT. cIMT was associated with age, smoking history, fasting glucose, systolic blood pressure, diastolic blood pressure and LDL. In multivariate regression analyses, triglyceride level (P = 0.04) remained a significant determinant of RH-PAT whereas systolic blood pressure (P = 0.02) and smoking pack-year history (P = 0.046) were significant determinants of cIMT.
Determinants of cIMT and RH-PAT were different, dominated by triglyceride and abdominal adiposity measures for RH-PAT but traditional risk factors including blood pressure, glucose, smoking and LDL for cIMT.
Endothelial function; carotid intima media thickness; atherosclerosis
The amount of cholesterol per LDL particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.
LDL-P measured by nuclear magnetic resonance (NMR) spectroscopy, calculated LDL-C, and carotid intima-media thickness (IMT) were assessed at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based cohort of 6814 persons free of clinical CVD at entry and followed for CVD events (n=319 during 5.5-year follow-up). Discordance, defined as values of LDL-P and LDL-C differing by ≥ 12 percentile units to give equal-sized concordant and discordant subgroups, was related to CVD events and to carotid IMT in models predicting outcomes for a 1 SD difference in LDL-C or LDL-P, adjusted for age, sex and race.
LDL-C and LDL-P were associated with incident CVD overall: hazard ratios (HR [95% CI]) 1.20 [1.08, 1.34] and 1.32 [1.19, 1.47], respectively, but for those with discordant levels, only LDL-P was associated with incident CVD (HR: 1.45 [1.19, 1.78]) (LDL-C HR: 1.07 [0.88, 1.30])). IMT also tracked with LDL-P rather than LDL-C, i.e., adjusted mean IMT of 958, 932, and 917 μm in the LDL-P > LDL-C discordant, concordant, and LDL-P < LDL-C discordant subgroups, respectively, with the difference persisting after adjustment for LDL-C (p=0.002) but not LDL-P (p=0.60).
For individuals with discordant LDL-C and LDL-P levels, the LDL-attributable atherosclerotic risk is better indicated by LDL-P.
LDL particle number; LDL cholesterol; cardiovascular disease risk; NMR; lipoproteins
Objective: To quantify the changes in blood glucose, blood lipids, blood pressure, and the intima-media thickness (IMT) of large arteries in patients with new-onset type 2 diabetes mellitus who received either intensive multifactorial treatment or conventional treatment. Methods: Two-hundred and ten patients with new-onset type 2 diabetes mellitus were randomly assigned to two groups: an intensive treatment group (n=110) and a conventional treatment group (n=100). Fasting blood glucose (FBG), glycosylated hemoglobin A1c (HbA1c), blood pressure, blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C)], and IMTs of large arteries (carotid, iliac, and femoral arteries) were determined before and at one and two years after starting treatment. The patients in the conventional treatment group received routine diabetes management in our outpatient department. Targets were established for patients in the intensive treatment group. Their blood glucose, blood lipids, and blood pressure levels were regularly monitored and therapeutic regimens were adjusted for those whose measurements did not meet the target values until all the parameters met the established targets. Within-group and between-group differences were evaluated. Results: A significantly greater percentage of patients in the intensive treatment group had LDL-C levels that reached the target value one year after starting treatment than those in the conventional treatment group (52.04% vs. 33.33%, P<0.05). No significant differences were found between groups for FBG, HbA1c, blood pressure, TG, TC, or HDL-C. The percentages of patients with TG (51.02% vs. 34.48%), TC (52.04% vs. 33.33%), and LDL-C (61.22% vs. 43.67%) who met the respective target values in the intensive treatment group were all significantly higher than the corresponding percentages in the conventional treatment group two years after starting treatment (P<0.05). There were no significant differences in the percentages of patients with FBG, HbA1c, and blood pressure values meeting the respective targets between the groups at the two-year follow-up. One year after starting treatment, the LDL-C level, diastolic blood pressure (DBP), and the IMTs of the femoral and iliac arteries of the intensive treatment group were significantly lower compared to those of the conventional treatment group (P<0.05), although there was no significant difference in other metabolic parameters. Two years after starting treatment, the TC, LDL-C, blood pressure [systolic blood pressure (SBP) and DBP], and the IMTs of the carotid and femoral arteries of the intensive treatment group were significantly lower than those of the conventional treatment group (P<0.05). No significant differences in other metabolic parameters existed between the two groups two years after starting treatment. Conclusions: Early comprehensive and intensive treatment of type 2 diabetes mellitus can delay or even reverse the increase in IMT of large arteries. Lowering blood pressure and blood lipid regulation in patients with type 2 diabetes mellitus have great significance in decreasing the risk of diabetes-related macrovascular lesions.
Type 2 diabetes mellitus; Intensive treatment; Intima-media thickness (IMT); Large arteries
Common carotid artery intima-media thickness (IMT), a measure of subclinical cardiovascular disease, changes during the cardiac cycle. The magnitude of this effect and its implications have not been well studied.
Methods and Results
Far-wall IMT measurements of the right common carotid artery were measured at end diastole and peak systole in 5633 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA). Multivariable regression models were generated with end-diastolic IMT, peak-systolic IMT, and change in IMT during the cardiac cycle as dependent variables and traditional cardiovascular risk factors as independent variables. The average age of our population was 61.9 (45 to 84) years. Average change in carotid IMT during the cardiac cycle was 0.041 mm (95% confidence interval: 0.039 to 0.042 mm), with a mean IMT of 0.68 mm. End-diastolic IMT and peak-systolic IMT were similarly associated with risk factors. In a fully adjusted model, change in carotid IMT during the cardiac cycle was associated with ethnicity and pulse pressure (P=0.001) and not age, sex, or other risk factors. Chinese and Hispanics had less of a change in IMT than did non-Hispanic whites. With peak-systolic IMT reference values used as normative data, 31.3% more individuals were classified as being in the upper quartile of IMT and at high risk for cardiovascular disease than would be expected when IMT is measured at end diastole.
Measurable differences in IMT are seen during the cardiac cycle. This affects the interpretation of IMT measurements used for cardiovascular risk assessment, given published normative data with IMT measured at peak systole.
Clinical Trial Registration
URL: www.ClinicalTrials.gov. Unique identifier: NCT00063440. (J Am Heart Assoc. 2012;1:e001420 doi: 10.1161/JAHA.112.001420.)
atherosclerosis; blood pressure; carotid arteries; diastole; epidemiology; risk factors; systole; ultrasonics
High cholesterol levels in circulating immune complexes (IC), surrogate markers of modified LDL, are associated with increased carotid intima-media thickness (IMT) and cardiovascular events in type 1 diabetes. Different modifications of LDL are involved in IC formation, but which of these are predictive of vascular events is not known. Therefore, we measured oxidized LDL (oxLDL), advanced glycation end products–modified LDL (AGE-LDL), and malondialdehyde-modified LDL (MDA-LDL) in IC and determined their relationship with increased carotid IMT and compared the strength of the association with that observed with conventional risk factors.
RESEARCH DESIGN AND METHODS
Levels of oxLDL, AGE-LDL, and MDA-LDL were measured in circulating IC isolated from sera of 479 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, collected at baseline. Internal and common carotid IMT were measured 8 and 14 years later by DCCT/EDIC.
OxLDL, AGE-LDL, and MDA-LDL levels in circulating IC were significantly correlated with diabetes duration, BMI, and lipid and blood pressure, but not with age. Multivariate logistic regression models indicated that individuals in the highest versus lowest quartile of oxLDL and AGE-LDL in IC had a 6.11-fold [confidence interval (CI) 2.51–14.8] and a 6.4-fold (CI 2.53–16.2) increase in the odds of having high carotid IMT, respectively, after adjusting for conventional risk factors. Parallel analyses resulted in odds ratios of 2.62 (CI 1.24, 5.55) for LDL-C, 1.45 (CI 0.69, 3.03) for diastolic blood pressure, and 2.33 (CI 1.09, 4.99) for A1C.
OxLDL and AGE-LDL in circulating IC were significantly associated with progression and increased levels of carotid IMT in type 1 diabetes.
Rosuvastatin (Crestor®; Astra Zeneca).
Rosuvastatin (5 mg).
Prevention of Atherosclerosis in Patients Living with HIV.
Phase of study:
To assess whether rosuvastatin therapy could slow the progression of the carotid intima-media thickness (C-IMT; as measured by the change in the mean IMT of the near and far walls of the distal common carotid arteries) over 2 years in HIV-infected patients (HIV-IP).
To assess whether rosuvastatin therapy could reduce highly sensitive C reactive protein (hs-CRP) inflammatory marker that is increased in HIV-IP.To assess the effect of rosuvastatin therapy on serum lipid levels (total cholesterol [TC], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and apolipoproteins (APO A1, APO B and APO B/A1).To assess the safety of rosuvastatin in HIV-IP through the evaluation of clinical laboratory analyses (liver function tests and creatine kinase) and adverse events (AEs).
Two-year randomized, double-blind, placebo-controlled, parallel group study.
Planned sample size:
Summary of eligibility criteria:
HIV-IP who are aged between 30 and 60 years, with a CD4 count. greater than 200 cells/mm3. Patients must be stable on combination antiretroviral therapy (cART) for at least 12 months and have a 10-year CVD risk of less than 20% (using the Framingham risk score).
Number of study centers:
Duration of treatment:
Two years (5 mg rosuvastatin or placebo once daily).
Dose and route of administration:
Oral rosuvastatin (5 mg) once daily.
The incidence of cardiovascular disease (CVD) in HIV-IP is at least three times higher than in the general population and further increases each year with combination anti-retroviral therapy (cART). The carotid atherosclerosis progression rate is 10 times higher in HIV-IP than in uninfected individuals. The aim of this study is to assess whether therapy with 5 mg rosuvastatin could:
1) Slow the progression in the mean IMT of the distal common carotid arteries over two years in HIV-IP.2) Change the concentration in the inflammatory marker – hs-CRP, which is increased in HIV-IP.3) Change the concentrations of TC, LDL cholesterol, HDL cholesterol, TG, apolipoproteins (APO) B, APO A1 and APO B/A1.4) Be administered safely in the study population.
Pharmacological intervention with rosuvastatin will be evaluated in a double-blind, placebo-controlled, randomized clinical trial in HIV-IP treated with cART not matching the published selection criteria for lipid-lowering therapy. For the first time, this study will investigate anti-inflammatory and anti-atherogenic effects of a pharmacological lipid-lowering agent in HIV-IP that may lead to the reduction of CVD.
rosuvastatin; atherosclerosis; cardiovascular disease; HIV; clinical trial protocol
Impact of multiple cardiovascular (CV) risk factors on the intima-media thickness (IMT) of femoral and carotid artery segments measured simultaneously has not been studied in asymptomatic adults. This study examined the impact of multiple CV risk factors on the IMT in asymptomatic adults.
Femoral and carotid IMT were measured by B-mode ultrasonography in 1080 asymptomatic subjects (aged 24–43 years) of the Bogalusa Heart Study.
In multivariate analyses, systolic blood pressure, age, male, total cholesterol/HDL cholesterol ratio and smoking were common independent predictor variables for the femoral and carotid IMT. Systolic blood pressure followed by age were the major determinant risk factors for the IMT of all arterial segments except carotid bulb for which age was the major predictor. The independent variables listed explained 11% of the variability in femoral IMT, 28% in common carotid, 18% in carotid bulb, 10% in internal carotid and 27% in composite carotid segments. Mean IMT increased with increasing number of risk factors in all arterial segments; p for trend = 0.003 for femoral and 0.001 for all carotid segments.
The observed deleterious trend of increasing IMT of the femoral and different segments of the carotid artery with increasing number of CV risk factors provide evidence of silent systemic atherosclerosis in asymptomatic young adults. These findings underscore the importance of multiple for risk factors profiling in early life. Studies of the femoral and carotid IMT may be helpful along with measurements of risk factors for evaluation of asymptomatic atherosclerotic disease.
femoral and carotid artery; intima-media thickness; risk factors; ultrasonography; arterial disease
Gender divergence on the impact of multiple cardiovascular (CV) risk factors on the femoral artery intima-media thickness (IMT) has not studied in a biracial (black-white) community based asymptomatic young adults.
Femoral IMT was measured by B-mode ultrasonography in 1080 individuals (aged 24- 43 years; 71%white, 43% male) enrolled in the Bogalusa Heart Study.
Femoral IMT showed a gender difference (males > females, p= 0.001), but no racial difference. In a multivariate model, age, cigarette smoking, systolic blood pressure and total to HDL cholesterol ratio related independently, in that order, to IMT in females; age and LDL cholesterol in males. In females, 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 to HDL 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, 1-2, 3 and 4-5 risk factors. There was no such significant trend in males.
Although males vs females had thicker IMT, the observed increasing trend of femoral IMT with increasing number of risk factors in asymptomatic young females suggests that females may be relatively more susceptible to the burden of multiple risk factors.
Femoral artery; intima-media thickness; risk factors; gender difference; ultrasonography
Increased dietary sodium has been reported to increase cardiovascular disease (CVD) risk, perhaps through blood pressure (BP) independent vascular remodeling. Carotid intima-media thickness (IMT) is an accepted measure of structural vascular remodeling and a strong predictor of CVD. This study aimed to determine whether urinary sodium is positively associated with carotid IMT in normotensive overweight and obese adults.
We evaluated baseline data from 258 participants in the Slow Adverse Vascular Effects (SAVE) Clinical Trial. Urinary sodium was measured from one 24-hour urine collection from each individual. Carotid IMT was measured using high resolution B-mode ultrasonography. Participants were categorized into quartiles of urinary sodium.
There was a significant positive trend with greater IMT associated with increasing urinary sodium quartile in univariate linear regression (P=0.047). This trend was significant when adjusting for age, sex, race, and systolic BP (SBP) (P=0.03) as well as in a fully adjusted model (P=0.04). In pairwise comparisons, the highest urinary sodium quartile had a significantly greater mean IMT (0.62 mm) than the lowest urinary sodium quartile (0.59 mm) after adjustment for age, sex, race, and SBP (P=0.04). This comparison lost significance after the addition of BMI.
In our community-based sample of normotensive overweight and obese adults, we observed a significant positive trend in carotid IMT with increasing quartile of urinary sodium. If the ongoing clinical trial confirms this relationship between sodium and carotid IMT, it would lend support to efforts to decrease sodium intake in overweight and obese individuals.
sodium; obesity; vascular remodeling; carotid IMT
Ezetimibe is a selective cholesterol absorption inhibitor with an excellent side-effect profile, able to reduce low-density lipoprotein (LDL) cholesterol by 15-25% from baseline in monotherapy and on top of statins and fibrates. Yet, it seems that ezetimibe produces quantitative rather than qualitative changes in LDL, with small net effects on atherogenic dyslipidaemia. This is supported by findings from the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression (ENHANCE) study on atherosclerosis progression, where the addition of ezetimibe to simvastatin in patients with heterozygous familial hypercholesterolaemia did not affect the mean change in carotid intima-media thickness, although a significant reduction in LDL cholesterol levels was observed. The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study has further shown that combination treatment with simvastatin significantly reduced LDL cholesterol levels in patients with aortic stenosis, but did not affect the primary end point of aortic valve and cardiovascular events, although a significant reduction in the risk of ischaemic events was reported. Formal cardiovascular outcome trials are underway and these will provide additional insights into the long-term effects of ezetimibe on clinical events as well as on atherogenic dyslipidaemia, beyond LDL cholesterol levels.
ezetimibe; cardiovascular risk; atherosclerosis; dyslipidaemia
BACKGROUND: Isolated office hypertension (IOH) has been accepted as a benign condition by some researchers, whereas others believe that it is associated with cardiovascular abnormalities and increased cardiovascular risk. The aim of this present study was to evaluate the effects of IOH on target organ damage and cardiovascular risk indices. METHODS: Arterial blood pressure (BP) measured in the office and by 24-hour ambulatory blood pressure measurement (ABMP), carotid intima-media thickness (CIMT), left ventricular mass index (LVMI), cardiothoracic index (CTI), duration of QTc, 24-hour microalbuminuria, fibrinogen, C-reactive protein (CRP), total cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol and triglyceride levels were evaluated. Thirty-three subjects with IOH (office BP > or = 140/90 mmHg and daytime ambulatory BP <135/85 mmHg), 17 patients with sustained hypertension (office BP > or = 140/90 mmHg and daytime ambulatory BP > or = 135/85 mmHg), and 17 normotensive control subjects were recruited in the study. The three groups were matched for age, sex and body mass index. RESULTS: CIMT was greater in patients with IOH than in normotensive subjects, and it was significantly lower than that of sustained hypertension patients. Significantly higher LVMI was determined in subjects with IOH compared to normotensive subjects. CTI, QTc, microalbuminuria, fibrinogen, CRP, total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels did not differ significantly among the three groups. CONCLUSIONS: IOH causes significant target organ damage and should not be regarded as a benign condition.
Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases. The Framingham risk score (FRS) is widely being used in the early prediction of coronary artery disease (CAD). However, the association between FRS and femoral artery IMT has not been studied in asymptomatic younger black and white adult population. Our objective was to examine the association between FRS and femoral artery IMT in asymptomatic younger adults.
Subjects (n = 1080; 71% white, 43% male) aged 24–43 years enrolled in the Bogalusa Heart Study. Femoral IMT was measured by B-mode ultrasonography. Age, gender, systolic blood pressure, diastolic blood pressure, Low density lipoprotein cholesterol, high density lipoprotein cholesterol, cigarette smoking and type2 diabetes were used to calculate individual FRS.
FRS was lower in females (p = 0.001) than males. Age-adjusted femoral IMT showed gender differences (males > females, p = 0.001) among whites only; and no race difference in both genders. A significant positive linear relationship between tertiles of FRS and IMT of femoral artery was noted in whites and blacks alike (p for trend < 0.0001). In a multivariate analysis that included FRS, race, body mass index (BMI), log insulin, log triglycerides, exercise and alcohol intake; FRS, insulin and BMI were significantly and independently associated in that order with femoral IMT.
The findings support the use of FRS in both white and black younger adults and underscore the importance of prevention and control of FRS variables in youth.
Femoral artery; intima-media thickness; Framingham risk score; ultrasonography; vascular disease
It has been previously documented that carotid intima-media thickness (cIMT) is a predictor of cardiovascular disease. The aim of this study was to identify clinical parameters associated with an increased cIMT treated hypertensive women. Female patients (n = 116) with essential hypertension, aged 40–65 years, were included in this study. Vascular ultrasound was performed and the patients were divided into two groups according to the values of cIMT (< or ≥0.9 mm). Patients with greater cIMT presented significantly higher systolic blood pressure and pulse pressure. Serum HDL-cholesterol was significantly lower and CRP was significantly higher in the same group. There was a significant correlation between cIMT and age (r = 0.25, P = 0.007), systolic blood pressure (r = 0.19, P = 0.009), pulse pressure (r = 0.30, P = 0.001), and LDL-cholesterol (r = 0.19, P = 0.043). cIMT was correlated to CRP (r = 0.31, P = 0.007) and negatively correlated to HDL-cholesterol (r = 0.33, P = 0.001). In logistic regression, only HDL-cholesterol, CRP, and pulse pressure were shown to be independent variables associated to increased cIMT. In conclusion, pulse pressure, HDL-cholesterol, and CRP are variables correlated with cIMT in treated hypertensive women.
Adiponectin and leptin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. Adiponectin inhibition could be expected to enhance cardiovascular metabolic risk. However, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk. We determined whether RA impacts on the independent relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and carotid intima-media thickness (cIMT) in 277 black African subjects from a developing population; 119 had RA. RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P < 0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (P = 0.0005), non-HDL cholesterol (P = 0.007), and triglyceride (P = 0.005) concentrations, total cholesterol-HDL cholesterol (P = 0.0002) and triglycerides-HDL cholesterol (P = 0.0003) ratios, and higher systolic (P = 0.0006), diastolic (P = 0.0004), and mean blood pressure (P = 0.0007) in RA but not non-RA subjects. Leptin was not associated with metabolic risk after adjustment for adiposity. The cIMT did not differ by RA status, and adipokine concentrations were unrelated to atherosclerosis. This study suggests that leptin and adiponectin inhibition may not alter overall cardiovascular risk and disease in RA.
To evaluate independent associations of high density lipoprotein cholesterol (HDL-C) and particle (HDL-P) concentrations with carotid intima-media thickness (cIMT) and incident coronary heart disease (CHD).
HDL-C is inversely related to CHD, but also to triglycerides, LDL particles (LDL-P), and related metabolic risk. HDL-P associations with CHD may be partially independent of these factors.
In a multi-ethnic study of 5598 men and women ages 45-84, without baseline CHD, excluding subjects on lipid-lowering medications, triglycerides >400 mg/dl or missing values, we evaluated associations of HDL-C and NMR-spectroscopy-measured HDL-P with cIMT and incident CHD (myocardial infarction, CHD death, angina, n=227 events, 6.0 years mean follow-up). All models were adjusted for age, sex, ethnicity, hypertension and smoking.
HDL-C and HDL-P correlated with each other (π=0.69) and LDL-P (π = −0.38, −0.25, respectively), p<0.05 for all. For (1-SD) higher HDL-C (15 mg/dl) or HDL-P (6.64 μmol/l), cIMT differences (95%CI) were −26.1(−34.7,−17.4) and −30.1 (−38.8,−21.4) μm, and CHD hazard ratios (HR (95%CI)) were 0.74 (0.63, 0.88) and 0.70 (0.59, 0.82), respectively. Adjusted for each other and LDL-P, HDL-C was no longer associated with cIMT (2.3 (−9.5, 14.2) μm) or CHD (0.97(0.77, 1.22)), but HDL-P remained independently associated with cIMT (−22.2(−33.8,−10.6) μm) and CHD (0.75 (0.61, 0.93)). Interactions by sex, ethnicity, diabetes and high-sensitivity C-reactive protein were not significant.
Adjusting for each other and LDL-P substantially attenuated associations of HDL-C, but not HDL-P, with cIMT and CHD. Potential confounding by related lipids or lipoproteins should be carefully considered when evaluating HDL-related risk.
Lipids; lipoproteins; high-density lipoprotein cholesterol; high-density lipoprotein particles; cardiovascular disease
This secondary analysis from the Stop Atherosclerosis in Native Diabetics Study examines the effects of lowering low-density lipoprotein cholesterol (LDL-C) with statins alone versus statins plus ezetimibe (E) on common carotid artery intimal medial thickness (CIMT) in patients with type 2 diabetes and no prior cardiovascular event.
It is unknown whether the addition of E to statin therapy affects subclinical atherosclerosis.
Within an aggressive group (target LDL-C ≤70mg/dL; non-high-density lipoprotein [non-HDL]-C ≤<100 mg/dL; systolic blood pressure [SBP] ≤115mmHg), change in CIMT over 36mos was compared in diabetic individuals >40 yrs receiving statins plus E versus statins alone. CIMT changes in both aggressive subgroups were compared with changes in the standard subgroups (target LDL-C ≤<100mg/dL; non-HDL-C ≤ 130 mg/dL; SBP ≤130mmHg).
Mean (95%CI) LDL-C was reduced by 31 (23, 37)mg/dL and 32 (27, 38)mg/dL in the aggressive group receiving statins plus E and statins alone, respectively, compared with changes of 1 (−3, 6) mg/dL in the standard group (p<0.0001 vs both aggressive subgroups. Within the aggressive group, mean IMT at 36mos regressed from baseline similarly in the E (−.025 [−05,.003] mm) and non-E subgroups (−.012 [−.03,.008] mm) but progressed in the standard treatment arm (0.039 [0.02, 0.06] mm), intergroup p<0.0001.
Reducing LDL-C to aggressive targets resulted in similar regression of CIMT in patients who attained equivalent LDL-C reductions from a statin alone or statin plus E. CIMT increased in those achieving standard targets.
ezetimibe; CIMT; atherosclerosis
Many studies showed a moderate cholesterol-lowering effect of plant sterols (PS), but increased circulating PS might be atherogenic. We evaluated the associations between natural dietary intake of PS and carotid intima–media thickness (IMT) and serum lipids.
This community-based cross-sectional study included 1160 men and 2780 women aged 31–75 years. Dietary intakes were assessed using a food-frequency questionnaire. The IMTs at the common, bifurcation and internal carotid artery segments, and fasting serum total (TC), LDL (LDLc) and HDL (HDLc) cholesterol, and triglycerides (TG) were determined. After adjusting for potential covariates, multivariate analysis showed a dose-dependent inverse association of total PS intake with serum TC, LDLc, non-HDLc in women (P<0.001) and in men (P<0.05). As compared to the lowest quartile of PS intake (<206 mg/d), the multivariate-adjusted means of TC, LDLc and non-HDLc in the highest quartile of PS intake (447 mg/d) decreased by 5.0%, 6.2% and 6.5% in women (P<0.005), and by 6.4%, 7.1% and 6.7% (P>0.05) in men. Although the IMTs tended to be lower with greater intake of dietary PS, only small differences in the left internal IMT between the highest and lowest groups were observed among men (−7.6%) and women (−5.1%) (P<0.05). The multivariate analysis showed no significant mean differences among the PS groups in HDLc, TG and IMTs at other studied sites among men and women (all P>0.05).
Greater PS consumption from natural diets is associated with lower serum total, LDL, non-HDL cholesterol and with thinner left internal IMT in women and men.
– To determine which of the National Cholesterol Education Program (NCEP) or National Health and Nutrition Examination Survey (NHANES) LDL-cholesterol and HDL-cholesterol classifications of dyslipidemia status in adolescents is most effective at predicting high common carotid artery intima-media thickness (IMT) in adulthood.
– Two classifications of pediatric dyslipidemia status have been proposed. No study has assessed which of these is most effective for predicting adolescents who will develop preclinical atherosclerosis in adulthood.
– Three population-based, prospective cohort studies that collected lipoprotein measurements on 1711 adolescents aged 12–18 years who were re-measured as young adults aged 29–39 years. Lipoproteins in adolescence were classified according to NCEP and NHANES cut-points, while high IMT in adulthood was defined as those at or above the age, sex, race, and cohort specific 90th percentile of IMT.
– Independent of the classification employed, adolescents with dyslipidemia were at significantly increased risk of having high IMT in adulthood (relative risks from 1.6 to 2.5). Differences in predictive capacity between both classifications were minimal. Overweight or obese adolescents with dyslipidemia had increased carotid IMT (males, 0.11mm; females, 0.08mm) in adulthood compared with those who did not have both risk factors. Adolescent dyslipidemia status was more strongly associated with high IMT in adulthood than change in dyslipidemia status.
– Pediatric dyslipidemia classifications perform equally in the prediction of adolescents who are at increased risk of high IMT in young adulthood. Our data suggest that dyslipidemia screening could be limited to overweight or obese adolescents.
pediatrics; dyslipidemia; carotid atherosclerosis; epidemiology; screening
Evidence of premature atherosclerosis and systemic arterial stiffening in patients after Kawasaki disease is accumulating.
To test the hypothesis that carotid intima‐media thickness (IMT), a surrogate marker of atherosclerosis, is associated with systemic arterial stiffness in children after Kawasaki disease.
A cohort of 72 patients was studied, comprising 26 patients with Kawasaki disease and coronary aneurysms (group I), 24 patients with Kawasaki disease and normal coronary arteries (group II) and 22 healthy age‐matched children (group III). The carotid IMT, carotid artery stiffness index, brachioradial pulse wave velocity (PWV), fasting total cholesterol, high‐density lipoprotein (HDL) cholesterol and low‐density lipoprotein (LDL) cholesterol were determined and compared among the three groups.
The carotid IMT was related to indices of arterial stiffness, and significant determinants of carotid IMT were identified by multivariate analysis. The mean (standard deviation (SD)) carotid IMT of both group I (0.41 (0.04) mm) and group II (0.39 (0.04) mm) was significantly greater than that of group III (0.36 (0.04) mm; p<0.001 and p = 0.008, respectively). For the entire cohort, carotid IMT correlated positively with LDL cholesterol (r = 0.31, p = 0.009), carotid artery stiffness index (r = 0.40, p = 0.001) and brachioradial PWV (r = 0.28, p = 0.016), but not with age, body mass index, systemic blood pressure, and HDL and total cholesterol. Multiple linear regression analysis identified carotid artery stiffness index (β = 0.25, p = 0.028) and subject grouping (β = −0.39, p = 0.001; model R2 = 0.29) as significant correlates of carotid IMT.
The increased carotid IMT in children after Kawasaki disease is associated with systemic arterial stiffening.
Many studies have shown that vegetarian diet has beneficial effects on the prevention of cardiovascular diseases. However, the effect of vegetarian diet on carotid intima-media thickness (IMT), as well as the association between IMT and duration of vegetarian diet, are still unclear. The present study aims to investigate the influence of duration of vegetarian diet on cardiovascular risk factors, and more importantly on IMT among Chinese vegetarians.
One hundred and seventy-one Chinese male vegetarians were screened for metabolic profile, cardiovascular risk and carotid IMT. They were compared with 129 age-matched omnivores recruited from a community-based health project. The effects of confounding factors were adjusted by stepwise logistic regression analysis.
Compared to the omnivores, the vegetarians had lower BMI, weight, systolic blood pressure and diastolic blood pressure. Also, the levels of triglyceride, total cholesterol, HDL-Cholesterol, LDL-Cholesterol, ApoA1, ApoB, uric acid, albumin and γ-glutamyltransferase were significantly reduced in vegetarians. Omnivores had significantly higher fasting blood glucose than that of vegetarians. However, there were no differences in fasting insulin, C-reactive protein and HOMA-IR between the two groups. IMT was thinner in the vegetarian group than in the omnivore group (0.59 ± 0.16 vs. 0.63 ± 0.10 cm, P < 0.05). The vegetarians were divided according to duration of vegetarian diet (< 6 years, 6 to ≤ 11 years, > 11 years), those in tertile 1 (< 6 years) and tertile 2 (6 to ≤ 11 years) had shown thinner IMT as compared to the omnivores, and tertile 3 had shown no reduction.
A decrease in multiple cardiovascular risk factors such as BMI, blood pressure and lipid profile was associated with vegetarian diet. Moreover, taking a low-calorie, low-protein, or vegetarian diet might have great beneficial effects on IMT through improved lipid profile, and the beneficial effects appeared to be correlated with the duration of vegetarian diet.
vegetarian diet; IMT; duration of vegetarian diet
Coronary heart disease (CHD) incidence and mortality remain very low in Japan despite major dietary changes and increases in CHD risk factors that should have resulted in substantial increase in CHD rates (Japanese paradox). Primary genetic effects are unlikely, given the substantial increase in CHD in migrant Japanese to the U.S. For men aged 40–49, levels of total cholesterol and blood pressure have been similar in Japan and the U.S. throughout their lifetime. The authors tested the hypothesis that levels of subclinical atherosclerosis, coronary artery calcification and intima-media thickness of the carotid artery (IMT), in men aged 40–49 are similar in Japan and the U.S. The authors conducted a population-based study of 493 randomly-selected men: 250 men in Kusatsu, Shiga, Japan, and 243 white men in Allegheny County, Pennsylvania, U.S. in 2002–2005. The Japanese had a less favorable profile of many risk factors than the whites. Prevalence ratio for the presence of coronary calcium score ≥10 in the Japanese compared to the whites was 0.52 (95% CI, 0.35, 0.76). Mean (SE) IMT was significantly lower in the Japanese (0.616 (0.005) versus 0.672 (0.005) mm, p<0.01). Both associations remained significant after adjusting for risk factors. The findings warrant further investigations.
Atherosclerosis; epidemiology; men; risk factors
Common carotid artery intima media thickness (IMT) is a measure of generalized atherosclerosis and has been shown to be associated with cognitive function. We examine two questions: does socioeconomic status (SES) moderate this association and is IMT more strongly associated with specific aspects of cognitive function?
Data are drawn from the Phase 7 (2003–2004) of the Whitehall II study (N=3896). In cross-sectional analyses the association between IMT and six measures of cognition (short term verbal memory, inductive reasoning, vocabulary, semantic and phonemic fluency and a measure of global cognitive status) was examined in analyses adjusted for previous history of coronary heart disease, health behaviours and other vascular risk measures such as blood pressure, cholesterol and body mass index.
The overall association between IMT and the 6 measures of cognition was restricted to the low SES group (p=0.02). Within this group, IMT was significantly associated with inductive reasoning (p=0.001), vocabulary (p=0.002), phonemic (p=0.006) and semantic fluency (p=0.02). The covariates examined explained about a quarter of the association between IMT and cognition in the low SES group. The associations with the measure of inductive reasoning (p=0.02), vocabulary (p=0.02) and phonemic fluency (p=0.04) remained after adjustment for all covariates.
SES is an important modifier of the association between IMT and cognition, an inverse association between the two was observed only in the low SES group. It is possible that high cognitive reserve among the high SES individuals prevents the functional manifestations of atherosclerosis. Verbal memory was not one of the cognitive domains associated with IMT.
cerebrovascular diseases; cognitive aging; carotid intima-media thickness
Mitral annular calcification (MAC) and aortic annular calcification (AVC) may represent a manifestation of generalized atherosclerosis in the elederly. Alterations in vascular structure, as indexed by the intima media thickness (IMT), are also recognized as independent predictors of adverse cardiovascular outcomes.
To examine the relationship between the degree of calcification at mitral and/or aortic valve annulus and large artery structure (thickness).
We evaluated 102 consecutive patients who underwent transthoracic echocardiography and carotid artery echoDoppler for various indications; variables measured were: systemic blood pressure (BP), pulse pressure (PP=SBP-DBP), body mass index (BMI), fasting glucose, total, HDL, LDL chlolesterol, triglycerides, cIMT. The patients were divided according to a grading of valvular/annular lesions independent scores based on acoustic densitometry: 1 = annular/valvular sclerosis/calcification absence; 2 = annular/valvular sclerosis; 3 = annular calcification; 4 = annular-valvular calcification; 5 = valvular calcification with no recognition of the leaflets.
Patient score was the highest observed for either valvular/annulus. Mean cIMT increased linearly with increasing valvular calcification score, ranging from 3.9 ± 0.48 mm in controls to 12.9 ± 1.8 mm in those subjects scored 5 (p < 0.0001). In the first to fourth quartile of cIMT values the respective maximal percentual of score were: score 1: 76.1%, score 2: 70.1%, score 4: 54.3% and score 5: 69.5% (p > 0.0001).
MAC and AVC score can identify subgroups of patients with different cIMT values which indicate different incidence and prevalence of systemic artery diseases. This data may confirm MAC-AVC as a useful important diagnostic parameter of systemic atherosclerotic disease.
carotid artery disease; heart disease; atherosclerosis; imaging
The aim of this study was to evaluate the association between resting baroreflex sensitivity (BRS) and carotid intima–media thickness (IMT), a putative marker of sub-clinical atherosclerosis. Participants were 64 men and 18 women (median age, 57 years; range, 40 to 70 years), who did not have a previous history of coronary artery disease or treatment for hypertension. Resting BRS was measured during a 9-min baseline period using the noninvasive sequence technique; carotid IMT was subsequently determined using ultrasonography. Hierarchical multiple regression analyses showed that greater IMT in the carotid bulb (an area with a high density of baroreceptors) was associated with reduced BRS. These findings remained after adjusting BRS for resting mean arterial pressure, age, body mass index, gender, and smoking history, R2 = 0.06, P = .03. In contrast, IMT in the common and internal carotid regions (areas with presumably lower baroreceptor densities) did not account for a significant proportion of the variance in BRS. These results suggest that subclinical atherosclerosis, specifically in a region with high baroreceptor density, is associated with a reduced sensitivity of the baroreflex.
Atherosclerosis; baroreflex sensitivity; blood pressure; carotid arteries; intima–media thickness