Plasma creatinine levels, estimated glomerular filtration rate and carotid intima media thickness in middle-aged women: a population based cohort study.

BACKGROUND AND AIM: The relationships between high Creatinine (Cr) levels or low estimated Glomerular Filtration Rate (eGFR) and common carotid Intima Media thickness (IMT) have been evaluated in a population-based cohort study in women, aged 30-69 (Progetto ATENA). METHODS AND RESULTS: Serum Cr and eGFR were measured in 310 women, as a part of 5.062. In this group carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. Women were classified by Cr levels >1 mg/dL or eGFR < 56 ml/min. Women with Cr > 1 mg/dL (90th percentile of creatinine distribution) or eGFR less than 56 ml/min (5th percentile of eGFR distribution) had relatively more carotid plaques as compared to the rest of the cohort. Multivariate logistic analysis, after adjustment for age, demonstrated a significant association between Cr (>1 mg/dL) and IMT (≥1.2 mm): OR 4.12 (C.I 1.22-13.86), p = 0.022; or eGFR (<56 ml/min) and IMT (≥1.2 mm): OR 4.31 (C.I 1.27-14.66), p = 0.019. CONCLUSIONS: These findings on an independent relationship between Cr and common carotid plaques in this population of middle aged women, independently of age, suggest the value of screening for early carotid disease in asymptomatic middle aged-women with mild renal insufficiency, in order to predict those at relatively higher risk for future cardiovascular events.

Association between atherogenic index of plasma and carotid intima-media thickness in a cohort of Mediterranean women.

The association between early atherosclerosis (IMT) and Atherogenic index of plasma (AIP), a marker of atherogenicity (log triglycerides/HDL Cholesterol) was evaluated in a population-based cohort study in women, aged 30-69, living in the metropolitan area of Naples, Southern Italy (Progetto ATENA). Serum cholesterol, HDL-cholesterol, LDL-cholesterol, Triglyceride, Insulin, HOMA, Apo B, hs-CPR were measured in 390 menopausal women, as a part of 5.062 participants of the cohort. Women in the second and third tertile of AIP showed an increased common carotid intima-media thickness compared with those in the first tertile: II vs I tertile (O.R. = 2.24, p = 0.007), III vs I tertile (O.R. = 2.29, p = 0.005), adjusted for age and Systolic pressure or II vs I tertile (O.R. = 2.19, p = 0.014), III vs I tertile (O.R. = 2.13, p = 0.026), adjusted for age, Systolic pressure, Body mass index and Apo B. Women in the second and third tertile of AIP compared to those in the first tertile, showed an OR of 2.14 (p = 0.016) and 1.99 (p = 0.033) respectively, of having elevates level of IMT, adjusted for traditional cardiovascular risk factor (age, Systolic Pressure, BMI, LDL Cholesterol, Diabetes diagnosis). This finding shows that in this group of menopausal women increased IMT is associated with elevated AIP independently of age and different cardiovascular risk factors. These results are in line with the hypothesis that AIP may be an useful clinical tools to give additional information in the risk assessment for atherosclerotic disease, in particular in postmenopausal women.

Carotid artery wall hypertrophy in children with metabolic syndrome.

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6+/-2.6 years; range 6-14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl(-1), fasting triglyceride concentration >100 mg dl(-1), fasting high-density lipoprotein cholesterol concentration <50 mg dl(-1) for females or <45 mg dl(-1) for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima-media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima-media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83+/-1.86 mm(2) [mean+/-s.d.] compared with the control group: 7.77+/-1.72 mm(2), P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.

Menstrual cycle length, serum lipids and lipoproteins in a cohort of Italian Mediterranean women: findings from Progetto ATENA.

BACKGROUND AND AIMS: Clinical studies suggest that menstrual irregularities are associated with metabolic and hormonal abnormalities, insulin resistance and a hyperestrogenic/hyperandrogenic imbalance, that may influence the risk of cardiovascular disease. METHODS AND RESULTS: The association of these abnormalities with the metabolic syndrome suggests that information on lipid patterns at different menstrual cycle length may be of interest in identifying women at higher cardiovascular risk. The association of lipid patterns with menstrual cycle length was evaluated in a cohort of 5062 women participating in the Progetto ATENA Study. Questions were administered to the participants about their cycle lengths at different periods of time over their reproductive life. The period between 20 and 50 years was investigated: normal cycle length was defined as short (30 days). Perimenopausal women were excluded and variables adjusted for age, BMI and menopausal status. In 4434 participants serum triglycerides were found to increase with an increased number of days in the menstrual cycle: 106 mg/dl in the short cycle pattern (21-26 days); 113 mg/dl in the medium cycle pattern (27-29 days); and 116 mg/dl in the long cycle pattern (30-31 days), whereas total and LDL cholesterol were found to be higher and HDL was lower in women with longer cycles, but the difference was not statistically significant. The results were very similar when the same adjusted analysis was restricted to a subgroup of 3823 women with a stable cycle length over the fourth and the fifth decade of life. CONCLUSIONS: These results suggest that cycle length may be a marker of higher cardiovascular risk due to associated metabolic and hormonal patterns.

Peripheral arterial circulation in individuals with impaired glucose tolerance.

Employees of a telephone company in Naples (N = 1376) were screened by oral glucose tolerance test (OGTT, 75 g). All those with impaired glucose tolerance (IGT) (N = 69) plus 138 normoglycemic controls, matched by sex, age, and body mass index (BMI, kg/m2), were selected to participate in this study. All participants were retested by OGTT under the same conditions as the first test. The prevalence of signs of impaired peripheral arterial circulation (IPAC) were investigated by different methods: Rose questionnaire on intermittent claudication, digital pulse plethysmography (inclination time), and ankle blood pressure measurement (ankle/arm systolic blood pressure). Very few persons had symptoms of IPAC: 2 (3.1%) and 3 (2.4%), respectively, in IGT subjects and controls. No difference in the prevalence of abnormal vascular parameters was detected between IGT and normoglycemic individuals according to either digital pulse plethysmography (6.1% versus 8.8%, P = 0.36) or ankle blood pressure measurement (10.8% versus 9.6%, chi 2 = 0.06, NS); similar results were obtained when the prevalence of abnormalities was evaluated according to both methods combined (16.9% versus 16.8%). The finding remained very much the same after controlling for the effect of smoking. Individuals with IGT at both OGTTs were compared with individuals with normoglycemia at both tests: once again no significant difference was detected between the two groups in the prevalence of abnormal vascular findings (22.6% versus 16.7%, chi 2 = 0.66, NS). This suggests that IGT is not associated with increased prevalence of atherosclerotic peripheral arterial disease.

LDL receptor cDNA sequence analysis in familial hypercholesterolemia patients: 5 novel mutations with high prevalence in families originating from southern Italy.

We screened a group of patients from southern Italy with clinically diagnosed familial hypercholesterolemia (FH) for mutations of the LDL receptor (LDLR) gene. RNA from each proband was analysed by RT-PCR followed by complete cDNA sequencing. Among 51 unrelated FH families we detected 17 mutations affecting the coding region of the LDLR gene. Five of these mutations, designated R395P, L783fsinsG, IVS15-3C>A, IVS3+5G>A, and 1698-1704delCACCCTAinsGCCCAAT (ITL545MPN), have not yet been reported in the literature. Interestingly, the novel IVS15-3C>A splicing mutation was detected in 20% of our unrelated FH families, suggesting an unusually high prevalence in our local population. Hum Mutat 17:433, 2001.

Site-specific atherosclerotic plaques in the carotid arteries of middle-aged women from southern Italy: associations with traditional risk factors and oxidation markers.

BACKGROUND AND PURPOSE: Studies on cardiovascular disease have preferentially involved men because of the lower frequency of the disease in preelderly women. The aim of this analysis was to examine, with the use of a standardized ultrasound protocol, a cohort of women to differentiate early atherosclerotic lesions in different carotid segments in relation to traditional (lipoprotein abnormalities, high blood pressure, cigarette smoking) and nontraditional (oxidation markers) cardiovascular risk factors. METHODS: More than 5000 clinically healthy, middle-aged women (n=5062; age range, 30 to 69 years) living in the area of Naples in southern Italy participated in the Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in the female population. A subsample of 310 participants underwent high-resolution B-mode ultrasound to assess intima-media thickness of common carotid artery and carotid bifurcation. RESULTS: Early atherosclerotic plaques (intima-media thickness >1.2 mm) were detected within the common carotid arteries in 37 women, in the carotid bifurcations in 77 women, and in both sites in 91 women. After age adjustment, common carotid plaques were found to be associated with higher systolic blood pressure (143 versus 138 mm Hg; P<0.05) and higher body mass index (29 versus 27 kg/m(2); P<0.01), while lesions at the carotid bifurcations were associated with higher LDL cholesterol (4.3 versus 3.8 mmol/L; P<0.01) and with smoking habit. Multivariate odds ratios for the presence of common carotid plaques were related to antibodies against oxidized LDL (odds ratio, 2.72; 95% CI, 1.46 to 5.07), and those for plaques at the bifurcation were related to lipid peroxides (odds ratio, 1.90; 95% CI, 1.04 to 3.47), and both relationships were independent of age, LDL cholesterol concentrations, body mass index, smoking habit, and systolic blood pressure. CONCLUSIONS: In a cohort of clinically healthy, middle-aged women, we found a site-specific association of traditional risk factors and oxidation markers with early atherosclerotic lesions in arterial segments differing in geometry, shear stress, extracellular matrix composition, and cell type populations.

Fractional fatty acid incorporation into human adipose tissue (FIAT) in hypertriglyceridemia.

Two processes regulate the removal of lipoprotein triglycerides from plasma: (1) hydrolysis of triglycerides by lipoprotein lipase to fatty acids in the capillaries; (2) local uptake and esterification of fatty acids by adipose tissue, muscle and other tissues. This second process has been studied on needle biopsy specimens of adipose tissue from normotriglyceridemic and hypertriglyceridemic subjects. Hypertriglyceridemie was found to be associated to low fatty acid incorporation into adipose tissue.

Prevalence of plaques and stenoses detectable by echo-Doppler examination in the femoral arteries of an elderly population.

Using echo-Doppler evaluation, we assessed the prevalence of possible atherosclerotic lesions in the common femoral arteries (n = 478) and superficial femoral arteries (n = 478) in 239 subjects (age range 65-94 years) living in retirement houses in Seattle. Ankle pressure was measured with a pneumatic cuff and a continuous wave Doppler. There were 68 individuals with an ankle arm index less than 0.97 and 39 of these with a index below 0.90. An echo-Doppler examination was performed with an Advanced Technologies Laboratories Mark 600 Duplex Scanner. We found 167 (34.9%) common femoral arteries affected by non-stenosing plaque while 19 arteries (4%) had stenosis or occlusion. In addition, 178 (37.2%) superficial femoral arteries showed non-stenosing plaques. The subjects with common femoral disease were 27 (11.3%), those with evidence of superficial femoral artery disease were 48 (20.1%), and those affected by disease in both sites were 84 (35.1%). There were 80 people (33.5%) with no ultrasound evidence of femoral artery disease. We found that the presence and severity of disease increased progressively in the decades 65-74, 75-84 and 85-94. We also demonstrated a positive association between major cardiovascular risk factors and ultrasound evidence of peripheral disease. The prevalence of femoral artery disease in an apparently healthy population was relatively high, although stenoses in most instances were not severe.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatty acid and glucose incorporation into human adipose tissue in non-insulin-dependent diabetes and in insulinoma. Inverse relations with plasma triglyceride and glucose concentrations.

Decreased fatty acid and glucose incorporation into human adipose tissue (FIAT and GLIAT) are frequently found in primary hypertriglyceridemia (HTG) and might also contribute to the defective removal of lipoprotein triglyceride (TG) in non-insulin-dependent diabetes mellitus (NIDDM). To study this possible mechanism, FIAT and GLIAT were determined in needle biopsy specimens from 14 patients with newly diagnosed NIDDM and in 14 age- and weight-matched controls. A patient with insulinoma and hyperinsulinism was also studied. FIAT and GLIAT processes were markedly reduced in patients with NIDDM that developed at the onset of maturity. Insulinoma patients, with normal plasma TG, showed FIAT-GLIAT values in the high to normal range before operation. A direct, highly significant correlation (P less than 0.001) was demonstrated between FIAT and GLIAT in diabetics, insulinoma and controls when considered together. Plasma TG and glucose concentrations were inversely related to FIAT and GLIAT. These relationships were independent of the degree of obesity. It is suggested that impaired FIAT and GLIAT might contribute to defective TG removal and HTG which are often demonstrated in NIDDM.

Increased blood flow to lower limbs after plasma exchange in two patients with familial hypercholesterolemia.

Leg blood flow was measured before and 1 and 7 days after plasma exchange by venous occlusion plethysmography in a 9-year-old girl with homozygous familial hypercholesterolemia and in a 41-year-old man with heterozygous familial hypercholesterolemia. In the first patient the plasma cholesterol level was reduced from 890 mg/dl to 532 mg/dl and 666 mg/dl 1 and 7 days after plasma exchange. In the second patient plasma cholesterol decreased from 596 mg/dl to 342 mg/dl and 480 mg/dl, respectively. Leg arterial flow increased from 8.5 ml/min/l of leg volume to 19.1 and 19.5 ml/min/l in the first patient and from 6.6 ml/min/l to 18.0 and 21.8 ml/min/l in the second. No change was observed in haematocrit and total globulin concentration, which are known to play an important role in blood viscosity and flow. It is concluded that plasma exchange, possibly by decreasing plasma cholesterol concentration in patients with familial hypercholesterolemia, is associated with improved arterial flow to lower limbs and it is suggested therefore that some beneficial effect might be found also in other vascular beds.

Improved reactive hyperemia test after plasma exchange in familial hypercholesterolemia.

By using a non-invasive methodology of vascular diagnosis, ECG-triggered strain-gauge plethysmography, 5 patients with familial hypercholesterolemia (FH) (3 homozygous, 2 heterozygous) were evaluated before and during the 1st and 2nd week after plasma exchange (PE). In order to obtain data on the responsiveness to vasodilating stimuli in FH patients undergoing PE, reactive hyperemia test and peak flow determination were also performed. Resting arterial flow over the calf was found to be significantly enhanced after PE. Reactive hyperemia test demonstrated persistent improvement of peak flow following exchange. This study demonstrates useful hemodynamic effects of PE in patients with FH.

Extracoronary atherosclerosis in familial hypercholesterolemia.

Sixty-two patients (31 males, 31 females) with familial hypercholesterolemia (FH) underwent a vascular examination by Doppler ultrasound. The ankle/arm systolic pressure index was determined, and serum lipoproteins were analyzed. Eight of 124 legs examined (6.5%) showed an ankle/arm pressure index less than 0.95, suggesting flow reducing stenosis. Common carotid, internal carotid, and iliac arteries were evaluated by echo Doppler examination with spectral analysis. Forty-five of the 372 arteries examined (12.1%) had detectable abnormalities at echo Doppler examination. Iliac and internal carotid artery lesions were significantly (P less than 0.01) more frequent among FH patients than in a control group (30 men, 20 women) comparable for sex and age. The mean age of the patients with heterozygous FH and detectable arterial lesions was 45.3 years and that of those without lesions 30.7 years (P less than 0.05). When 14 patients with heterozygous FH and arterial lesions were compared to another 14 without lesions and matched for age and gender, it was found that patients with lesions had on average lower concentrations of HDL-cholesterol, and that 10 of 14 cases were actual smokers.

Plasma vitamin E, apolipoprotein B and HDL-cholesterol in middle-aged men from southern Italy.

Plasma vitamin E, HDL-cholesterol, apolipoprotein B and triglycerides were measured in an apparently healthy, male, random population sample (n = 74) from Southern Italy. Plasma vitamin E concentration was positively correlated to that of serum cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B (all P less than 0.001). The results of partial correlation analysis showed that apo B, the apolipoprotein constituent of LDL, was related to vitamin E independently of serum triglycerides, a fairly accurate marker of VLDL. On the other hand, triglycerides were related to vitamin E independently of apo B. Both correlations were much weaker if an adjustment was performed for non-HDL-cholesterol. No independent relationship was demonstrated between plasma vitamin E and HDL-cholesterol.

Changes of systolic time intervals in asymptomatic patients with primary hyperlipoproteinemia.

Previous studies have focused on the usefulness of systolic time intervals to assess changes of myocardial function. In a recent report, hyperlipoproteinemia (HLP) was shown to induce early signs of vascular disease in asymptomatic subjects. By means systolic time intervals (STI) we studied left ventricular functions in normal subjects and asymptomatic patients with HLP, who showed normal response to exercise on a bicycle ergometer. The results showed mean values of STI for the population in the normal range, according to standards accepted in North American reports. Different values of STI were found when we compared the data of controls with the STI of HLP patients with higher values of PEPI and PEP/LVET and lower values of LVETI in HLP patients. These results suggest that hyperlipoproteinemia affects STI in asymptomatic patients, probably as a sign of early impairment of left myocardial function.

Abnormalities in serum lipoprotein composition in patients with premature coronary heart disease compared to serum lipid matched controls.

Serum lipoprotein composition was examined in 18 male patients (mean age 44 +/- 0.9 years) who had undergone coronary artery by-pass surgery because of premature coronary heart disease (PCHD) and in 18 control subjects, matched with patients for sex, age, body mass index and serum cholesterol and triglyceride. Cholesterol, triglyceride and apolipoprotein B (apo B) concentrations in very low density lipoprotein (VLDL) and in low density lipoprotein (LDL) did not differ in the two groups, but high density lipoprotein (HDL)-cholesterol was significantly lower in PCHD patients (P less than 0.02). Cholesterol/apo B, triglyceride/apo B and phospholipid/apo B ratios in VLDL were significantly higher in patients than in controls (P less than 0.05, P less than 0.01 and P less than 0.001, respectively). The relative VLDL enrichment in cholesterol was mainly due to the non-esterified moiety (P less than 0.01). These VLDL abnormalities as well as the low HDL-cholesterol suggest an impairment of VLDL catabolism in PCHD patients.

Relative protection from cerebral atherosclerosis of young patients with homozygous familial hypercholesterolemia.

It is well known that hypercholesterolemia is correlated with coronary atherosclerosis, but no definite information is available on its association with cerebrovascular atherosclerosis. We studied 10 young patients (age 3-32 years) with homozygous familial hypercholesterolemia (FH), together with 3 normal relatives as healthy controls. Extra- and intracranial Doppler examination, MRI and cerebral blood flow by SPECT and 99mTc-HM-PAO were performed on all. Six out of 10 patients already had signs and symptoms of coronary heart disease, but all patients were free from ischemic brain lesions, as small as detectable at MRI, and had normal cerebral blood flow. Two patients presented significant stenosis of the carotid arteries at Doppler examination. Young patients with homozygous FH have early and clinically evident coronary atherosclerosis, while overt disease in the cerebral district is delayed despite the extremely elevated plasma cholesterol concentration. This was also confirmed by the autopsy of two patients, who died after the study and whose cerebral arteries were totally free from atherosclerotic lesions. The age, at which flow-reducing atherosclerotic lesions develop in hypercholesterolemic patients, differs with regard to the arterial district involved.

Effects of alpha-adrenergic and beta-adrenergic receptor blockade on lipid metabolism.

The role of lipoprotein lipase in the pathophysiology of lipid changes during alpha-receptor or beta-receptor blockade was evaluated in this clinical trial. Thirty hypertensive patients were given 2 mg of prazosin twice daily or 100 mg of metoprolol twice daily for 10 weeks, according to an open, randomized protocol. Both drugs were effective in reducing arterial blood pressure (from 153 +/- 16/102 +/- 6 mm Hg to 146 +/- 12/92 +/- 8 mm Hg with prazosin and from 158 +/- 17/103 +/- 8 to 144 +/- 14/94 +/- 10 mm Hg with metoprolol). Prazosin significantly reduced total plasma cholesterol from 202 +/- 39 to 188 +/- 36 mg/dl and increased high-density lipoprotein cholesterol from 36 +/- 8 to 40.5 +/- 11 mg/dl. Prazosin did not affect plasma triglycerides levels, whereas patients taking metoprolol had a slight rise in these levels, from 122 +/- 42 to 142 +/- 57 mg/dl, along with a decrease in high-density lipoprotein cholesterol from 37 +/- 10 to 31 +/- 8 mg/dl. The concentration of apoprotein B did not change significantly with either treatment. Lipoprotein lipase activity increased in the prazosin group from 28.4 +/- 16 to 37.7 +/- 14 mumol/liter per minute (p less than 0.01), but did not change significantly (29.9 +/- 12 versus 32.8 +/- 8 mumol/liter per minute) in patients treated with the beta blocker. These data, which confirm previous reports of serum lipid changes during antihypertensive therapy, suggest that alpha1 blockers may interfere with lipoprotein lipase, possibly by reducing its catecholamine-mediated inactivation.

Pravastatin reduces carotid intima-media thickness progression in an asymptomatic hypercholesterolemic mediterranean population: the Carotid Atherosclerosis Italian Ultrasound Study.

PURPOSE: The Carotid Atherosclerosis Italian Ultrasound Study (CAIUS) was performed to test the effects of lipid lowering on the progression of carotid intima-media thickness (IMT) in 305 asymptomatic patients from a Mediterranean country. PATIENTS AND METHODS: Eligibility included hypercholesterolemia (baseline means: low-density lipoprotein [LDL] = 4.68 mmol/L, high-density lipoprotein [HDL] = 1.37 mmol/L), and at least one 1.3 < IMT < 3.5 mm in the carotid arteries. Patients (mean age 55 years, 53% male) were assigned to pravastatin (40 mg/day, n = 151) or placebo (n not equal to 154). Ultrasound imaging was used to quantify IMT at baseline, and semiannually thereafter for up to 3 years. The mean of the 12 maximum IMTs (MMaxIMT), was calculated for each patient visit, and used to determine each patient's longitudinal progression slope. The intention-to-treat group difference in the MMaxIMT progression was chosen a priori as the primary end point. RESULTS: Five serious cardiovascular events (1 fatal myocardial infarction), and 7 drop-outs for cancer were registered. In the pravastatin group, LDL decreased -0.22 after 3 months versus -0.01 in the placebo group, and remained substantially unchanged afterward (-0.23 versus +0.01 at 36 months, respectively). Progression of the MMaxIMT was 0.009 +/- 0.0027 versus -0.0043 +/- 0.0028 mm/year (mean +/- SE, P < 0.0007) in the placebo and pravastatin groups, respectively. IMT progression slopes diverged after 6 months of treatment. CONCLUSIONS: Pravastatin stops the progression of carotid IMT in asymptomatic, moderately hypercholesterolemic men and women. This finding extends the beneficial effects of cholesterol lowering to the primary prevention of atherosclerosis in a population with relatively low cardiovascular event rates, and suggests that this benefit is mediated by specific morphological effects on early stages of plaque development.

Baseline reproducibility of B-mode ultrasonic measurement of carotid artery intima-media thickness: the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND AND OBJECTIVE: The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline. METHOD: To evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers. RESULTS: The overall coefficient of reliability (R) was 0.859 for CBM(max), 0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866. CONCLUSION: The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.