Endothelium-dependent flow-mediated vasodilatation, insulin resistance and the metabolic syndrome in 60-year-old men.

OBJECTIVES: To evaluate the endothelium-dependent flow-mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60-year-old clinically healthy men. SUBJECTS: The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO). METHODS: Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin-mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity. RESULTS: The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin-mediated glucose uptake (r = -0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11). CONCLUSION: In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60-year-old men.

Multiple risk intervention trial in high risk hypertensive men: comparison of ultrasound intima-media thickness and clinical outcome during 6 years of follow-up.

OBJECTIVES: The objective was to analyse whether a favourable change in risk factors, caused by a comprehensive risk factor modification programme, affected intima-media thickness (IMT) in the common carotid artery, and whether any such change was associated with a change in cardiovascular events during a 6-year follow-up. DESIGN: Patients were randomized 1 : 1 to special intervention or usual care. SETTING: Hypertension Unit at university hospital. SUBJECTS: A total of 164 patients were randomized. Inclusion criteria were male, aged 50-72 years (at randomization) and one or more of the following: Serum cholesterol level > 6.5 mmol L(-1), smoking or diabetes mellitus. All patients were prescribed antihypertensive treatment since many years. In 142 men good quality ultrasound recording of the common carotid IMT were achieved at baseline, 119 were re-examined after 3.3 years, and 97 patients were available for examination after mean follow-up time of 6.2 years. Cardiovascular events were available for all randomized patients. INTERVENTIONS: The nonpharmacological special intervention programme was based on one information meeting followed by five weekly 2-h sessions with participation of patients and spouses. The diet recommendations were similar to established guidelines. Overweight patients were instructed to lose weight, and diabetic patients were systematically taught self-monitoring of blood glucose. Smokers were invited to a smoking cessation programme with five weekly meetings. Follow-up visits were thereafter scheduled every 6 months. Lipid lowering drugs were recommended in the intervention group if the treatment goals using nonpharmacological measures were not achieved. Patients in the usual care group were told to quit smoking and to lower their consumption of fat and glucose. Antihypertensive treatment (i.e., selection of drugs) was on purpose kept similar in the two groups. MAIN OUTCOME MEASURES: The IMT of the common carotid artery as measured by ultrasound. Cardiovascular events during follow-up. RESULTS: Significant net reductions were seen for serum cholesterol, triglycerides, fasting glucose and smoking. No difference in change in IMT was observed during follow-up between the two randomization groups. The explanation was that patients with positive plaque status at baseline had a much larger increase in IMT over time than patients with negative plaque status, and that patients with positive plaque status more often survived and were available for re-examination after 6 years in the intervention group than in the usual care group. Total mortality was lower in the intervention group, compared with the usual care group, 13 and 29%, respectively (P=0.028). CONCLUSIONS: In high risk populations, long-term studies with surrogate endpoints may be misleading because of missing data in patients where a large increase in IMT would have been observed, had they been re-examined. Another important conclusion from our study was that the gloomy prognosis for this patient category may be improved by a dedicated risk factor intervention programme. The improved prognosis was observed mainly in those patients at highest risk judged from history of cardiovascular disease or positive ultrasound plaque status at baseline.

A multiscale dynamic programming procedure for boundary detection in ultrasonic artery images.

Ultrasonic measurements of human carotid and femoral artery walls are conventionally obtained by manually tracing interfaces between tissue layers. The drawbacks of this method are the interobserver variability and inefficiency. In this paper, we present a new automated method which reduces these problems. By applying a multiscale dynamic programming (DP) algorithm, approximate vessel wall positions are first estimated in a coarse-scale image, which then guide the detection of the boundaries in a fine-scale image. In both cases, DP is used for finding a global optimum for a cost function. The cost function is a weighted sum of terms, in fuzzy expression forms, representing image features and geometrical characteristics of the vessel interfaces. The weights are adjusted by a training procedure using human expert tracings. Operator interventions, if needed, also take effect under the framework of global optimality. This reduces the amount of human intervention and, hence, variability due to subjectiveness. By incorporating human knowledge and experience, the algorithm becomes more robust. A thorough evaluation of the method in the clinical environment shows that interobserver variability is evidently decreased and so is the overall analysis time. We conclude that the automated procedure can replace the manual procedure and leads to an improved performance.

Weight loss and progression of early atherosclerosis in the carotid artery: a four-year controlled study of obese subjects.

OBJECTIVE: To investigate the extent of carotid artery atherosclerosis in obese subjects and to examine the possible effects of weight loss on atherosclerotic development. DESIGN: Controlled 4 y intervention study. SUBJECTS: 20 obese patients treated with weight-reducing gastroplasty, 19 obese patients treated with dietary recommendations and 35 lean subjects. MEASUREMENTS: Body weight, blood pressure, blood lipids, glucose and insulin were measured. A B-mode ultrasound was recorded to determine the intima-media thickness (IMT) and lumen diameter (LD) of the carotid artery. Study groups were investigated at baseline and re-examined after 3 to 4 y of follow-up. RESULTS: At baseline, obese patients had higher blood pressure, serum total cholesterol, triglycerides, glucose and insulin compared with lean subjects; they also had a larger IMT in the carotid artery bulb (P<0.05) and a larger LD in the common carotid artery (P<0.01). After 4 y of follow-up, obese patients treated with surgery displayed a mean weight loss of 22 kg (19%), while the average weight in the obese control group remained unchanged (P<0.001). The weight loss group showed improvements in blood pressure, HDL-cholesterol, triglycerides and insulin compared with the obese control group (P<0.05). The progression rate of carotid bulb IMT in the weight loss group was similar to that observed in the lean control group (0.024 vs 0.025 mm/y, n.s.), whereas the IMT progression rate was almost three times higher in the obese control group (0.068 mm/y, P<0.05 compared with lean controls). CONCLUSION: Obese people have an unfavourable risk factor profile and signs of premature carotid artery atherosclerosis. Weight loss is followed by an improvement in several risk factors and may reduce the progression rate of atherosclerotic changes in the carotid artery bulb.

Adding ischaemic hand exercise during occlusion of the brachial artery increases the flow-mediated vasodilation in ultrasound studies of endothelial function.

A non-invasive method has been introduced to study endothelial function by evaluating flow-mediated, endothelium-dependent vasodilation of the brachial artery. One weakness of this method is that the post-occlusion vasodilation response is very small in subjects above the age of 60 years, which is a problem when quantifying endothelial dysfunction above this age. We have therefore evaluated whether a higher post-occlusion flow stimulus and a larger vasodilation response can be achieved by adding ischaemic hand exercise during the occlusion of the brachial artery. The subject population was men (n = 12), aged 60 years, free from cardiovascular disease. B-mode ultrasound images for the measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery. Blood flow velocity was recorded intermittently using a Doppler technique. Hyperaemia was induced in two different ways: first by occlusion only and then by adding ischaemic hand exercise during the occlusion. The results showed that flow velocity was higher and the duration of flow increase was longer after ischaemic hand exercise compared with occlusion only. Two minutes after cuff pressure release, the increase in blood flow velocity was significantly higher after ischaemic hand work compared with occlusion only (P < 0.01). The corresponding maximal lumen diameters after cuff pressure release were 4.63 +/- 0.35 and 4.45 +/- 0.34 respectively (P < 0.01). The flow-mediated vasodilation increased significantly from 2.24 +/- 2.00% after occlusion only to 7.42 +/- 3.32% after occlusion plus ischaemic hand exercise (P < 0.01). In conclusion, this study showed that a maximal endothelial-dependent vasodilation was not achieved after occlusion only in these 60-year-old men. Adding ischaemic hand exercise may therefore be of value when quantifying endothelial dysfunction in this age group.

How can the variability in ultrasound measurement of intima-media thickness be reduced? Studies of interobserver variability in carotid and femoral arteries.

A critical component in scientific studies of most biological variables is the variation or error in measurements which leads to non-identical results of repeated measurements from the same subject. The aim of this study was to investigate whether the interobserver error (s) in measurement of intima-media thickness (IMT) in carotid and femoral arteries could be decreased if the mean value obtained using two ultrasound images from each of the right and left arteries was used in the analyses instead of the mean value obtained using images from only the right artery. In addition, we wished to evaluate two different reading procedures, one based on manual tracing of echo interfaces and the other on automated edge detection. In a methodological study, 50 subjects were examined with ultrasound twice in the same day by two independent laboratory technologists. The ultrasound images were analysed in two ways: using a computerized manual tracing analysing system and an automated analysing system. When both right and left carotid arteries were examined (manual reading), the interobserver error was smaller than that determined for the examination of only the right artery, for IMTmean in both the common carotid artery (P = 0.06) and the carotid artery bulb (P < 0.05). The interobserver error was also significantly smaller for double-sided vs. one-sided examination with automated reading of IMTmean in the common carotid artery (P < 0.01) and in the carotid artery bulb (P < 0.01). The coefficient of variation (CV) for measurement in the common carotid artery decreased from 8.6% (one-sided, manual reading) to 5.3% (double-sided, automated reading). The interobserver error in measurement of IMT in the common femoral artery did not improve by examination of both right and left arteries. The results from this study show that the interobserver errors in measurement of IMT can be decreased by using ultrasound images from both the right and the left carotid arteries, and that the use of an automated analysing system greatly simplifies the reading of ultrasound images with sustained low variability.

Antibody titers against oxidized LDL are not elevated in patients with familial hypercholesterolemia.

Antibodies against oxidized low density lipoproteins (Ox-LDLs) have been proposed to be independent predictors of atherosclerosis development. The main aims of the current study were to (1) compare antibody titers to Ox-LDL in patients with heterozygous familial hypercholesterolemia (n=51) with those in matched controls (n=45) and (2) analyze whether the antibody titers were related to the extent of atherosclerosis, as assessed cross-sectionally and prospectively by ultrasonography in the 2 study groups. Antibody titers were determined with a solid-phase ELISA, and plates were coated with the antigens Ox-LDL or malondialdehyde-treated LDL (MDA-LDL) as well as with the postcoat only (5% dry milk powder). Antibody titers were expressed as absorbance [(value in patient serum minus that in postcoat) divided by (Internal Standard Serum minus postcoat)]. There were no significant differences in antibody titers against Ox-LDL or MDA-LDL between the group of patients with familial hypercholesterolemia and the controls. In cross-sectional comparisons, no significant associations were observed between the intima-media thickness of the carotid or femoral arteries and antibody titers against Ox-LDL or between plaque occurrence and these titers. Patients with a history of myocardial infarction had significantly lower IgM titers against Ox-LDL compared with patients without a history of myocardial infarction and with controls. In conclusion, mean values for antibody titers against Ox-LDL were not increased in the patient group compared with a healthy control group, and no positive, significant relationship was observed between antibody titers and the extent of atherosclerosis, as measured by ultrasound, in the carotid or femoral arteries. Taken together, these findings indicate that the relationship between the autoimmune response to Ox-LDL and the extent of atherosclerosis is more complex than previously anticipated.

A new automated computerized analyzing system simplifies readings and reduces the variability in ultrasound measurement of intima-media thickness.

BACKGROUND AND PURPOSE: A computerized analyzing system with manual tracing of echo interfaces for measurement of intima-media thickness and lumen diameter in carotid and femoral arteries was previously developed by our research group and has been used for many years in several laboratories. However, manual measurements are not only time consuming, but the results from these readings are also dependent on training and subjective judgement. A further problem is the observed drift in measurements over time. A new computerized technique for automatic detection of echo interfaces was therefore developed. The aim of this study was to evaluate the new automated computerized analyzing system. METHODS: The new system is based on dynamic programming and includes optional interactive modification by the human operator. Local measurements of vessel echo intensity, intensity gradient, and boundary continuity are extracted by image analysis techniques and included as weighed terms in a cost function. The dynamic programming procedure is used for determining the optimal location of the vessel interfaces in a way that the cost function is minimized. RESULTS: With the new automated computerized analyzing system the measurement results were less dependent on the reader's experience, and the variability between readers was less compared with the old manual analyzing system. The measurements were also less time consuming. CONCLUSIONS: The new automated analyzing system will not only greatly increase the speed of measurements but also reduce the variability between readers. It should also reduce the variability between different laboratories if the same analyzing program is used. Furthermore, the new system will probably prevent the problem with drift in measurements over time.

Atherosclerotic changes in the carotid artery bulb as measured by B-mode ultrasound are associated with the extent of coronary atherosclerosis.

BACKGROUND AND PURPOSE: Ultrasound is increasingly used to measure atherosclerotic development in carotid and femoral arteries. The aim of this study was to investigate the relationship between coronary atherosclerosis as measured by quantitative angiography and peripheral atherosclerosis as measured by ultrasound in three different arterial regions. METHODS: Patients (n = 32) with at least two coronary segments with visible signs of atherosclerosis as defined in a computer-assisted analysis of coronary angiograms were also examined with B-mode ultrasound. The extent of coronary atherosclerosis was expressed as the average diameter stenosis of coronary segments, and peripheral atherosclerosis was defined as intima-media thickness (IMT) and plaque occurrence in the common carotid artery, the carotid bulb, and the common femoral artery. RESULTS: The results showed a significant correlation between the ultrasound measurement of IMT of the carotid bulb and diameter stenosis of the included coronary segments (r = .68, P = .01) and of carotid plaques and diameter stenosis (P < .001). The correlation between common carotid IMT and diameter stenosis of included coronary segments was not statistically significant (r = .31, NS). There were no significant relationships between common femoral IMT or femoral plaques and diameter stenosis of included coronary segments. CONCLUSIONS: Although this study is small, it points to a very important aspect of ultrasound measurements of atherosclerosis: measurements performed in the common carotid artery or the femoral artery may not relate to coronary atherosclerosis in the same way as measurements performed in the carotid bulb. The findings underline the importance of measuring IMT not only in the common carotid artery but also in the carotid bulb and present data separately. These results have to be confirmed in a larger-scale study.

Atherosclerotic disease in the femoral artery in hypertensive patients at high cardiovascular risk. The value of ultrasonographic assessment of intima-media thickness and plaque occurrence. Risk Intervention Study (RIS) Group.

The aim of the present investigation was to examine the occurrence of ultrasound-assessed morphological changes in the right common femoral artery and relate these findings to the ankle-arm index and to symptoms of lower-extremity arterial disease in hypertensive men at high cardiovascular risk (n = 143). Comparisons were made with a healthy reference group consisting of age-matched men at low risk (n = 46). The results showed that it was possible to obtain high-quality measurements of intima-media thickness in about 80% of all men and that the intraobserver variability was satisfactory (14%). A normal mean intima-media thickness was defined, using data from the low-risk group. Plaque occurrence and mean intima-media thickness in the right common femoral artery were significantly associated with ankle-arm index both in the right and left leg. There were more and larger plaques, as well as thicker mean and maximum intima-media complexes, in the high-risk group than in the low-risk group. In the high-risk group, 11% suffered from symptoms of right lower-extremity artery disease, 20% had an ankle-arm index < or= 0.9, 62% had moderate or large plaques (compared with 28% in the low-risk group, P < .001), and 77% had an enlarged intima-media complex. The cumulative frequency of signs of atherosclerosis in the right leg was 81% among the 110 patients in whom complete results from all examinations were available. Our conclusion is that ultrasound measurement of the intima-media thickness of the common femoral artery is a valuable method to evaluate morphological changes related to atherosclerotic disease in the lower extremity.

On quantifying plaque size and intima-media thickness in carotid and femoral arteries. Comments on results from a prospective ultrasound study in patients with familial hypercholesterolemia.

The aim of the present analysis in an ongoing observational study was to evaluate the possibility of measuring plaque size in ultrasound images from carotid and femoral arteries and the usefulness of quantitative plaque measurements in such a prospective study. Twenty-five patients with carotid plaques were identified in a group of patients with familial hypercholesterolemia (n = 50) compared with 7 subjects in a low-risk control group (n = 47). Only 20 of the 32 recorded plaques were accessible for quantitative follow-up measurements of area, base length, and thickness, which represents only 21% of all subjects investigated. In contrast, paired observations of intima-media thickness in the common carotid artery were available in 98% and in the carotid bulb in 87% of the subjects investigated. In those with paired observations of plaque area available, the data indicated a close relationship between the 2-year change recorded in plaque area and the 2-year change in intima-media thickness measured in a 10-mm-long predefined section of the carotid bulb (r = .81, P < .001, n = 19). The corresponding relationship between change in plaque area and change in a 10-mm-long section of the common carotid artery was r = .38 and P < .05 (n = 20). Quantitative measurements of plaques in the femoral arteries were also performed, but the results from these measurements were in most cases judged not to be useful. However, measurements of intima-media thickness in a 15-mm-long predefined section of the common femoral artery may be performed in a reproducible way in most patients. We conclude that the usefulness of plaque area measurements in prospective studies of the carotid artery seems limited because plaques available for quantitative measurements are present in only a small proportion of subjects. However, reproducible measurements of intima-media thickness in a predefined section of the carotid bulb are achievable in most subjects, and our data indicate that the changes recorded over time in the carotid bulb closely mirror changes occurring in the size of atherosclerotic plaques within the carotid artery region. In addition, present data indicate that measurements of intima-media thickness in the common carotid artery complement measurements performed in the carotid artery bulb in the study of early atherosclerosis.

Multiple risk intervention in high-risk hypertensive patients. A 3-year ultrasound study of intima-media thickness and plaques in the carotid artery. Risk Intervention Study (RIS) Group.

In spite of optimal blood pressure control, available data indicate that the risk of coronary heart disease remains high in many patients with hypertension. Multifactorial risk intervention programs have therefore been advocated. The aim of the present randomized study was to analyze whether a favorable change in risk factors caused by a comprehensive risk factor modification program (focused mainly on nonpharmacological intervention) might beneficially affect ultrasound-assessed far-wall common carotid intima-media thickness or plaques in the carotid artery in high-risk hypertensive patients (n=81) in comparison with those undergoing usual care (n=83). A further aim was to analyze whether risk factors measured at baseline or follow-up were related to the change recorded in intima-media thickness during follow-up. The results showed in the intervention group a favorable change in LDL cholesterol (-9%), in smoking habits (32% of smokers quit smoking), and in HbA1c (-17% in patients with diabetes mellitus) over the 3.5-year observation period. However, no difference between the two randomization groups could be observed for far-wall common carotid intima-media thickness or plaque status during follow-up. Of all tested potential risk factors, only fasting insulin at baseline (available in nondiabetic patients) was significantly related to the change in mean intima-media thickness during follow-up (r=.25, n=92, P<.01). The relationship (negative) between follow-up serum HDL and change in mean intima-media thickness during the preceding follow-up was of borderline significance. Patients with moderate to large plaques in the carotid artery region at baseline had a significantly larger increase in common carotid artery intima-media thickness during follow-up than patients with no or only small plaques. The results are disappointing and may indicate that either the change in risk factors occurred too late in life or a considerably larger change in concomitant risk factors than we observed is needed to favorably affect intima-media thickness during an observation period of around 3 years in high-risk hypertensive patients.

Femoral artery wall morphology, hemostatic factors and intermittent claudication: ultrasound study in men at high and low risk for atherosclerotic disease.

The aim of this study was to examine whether there was a relationship between ultrasound-assessed morphology of the femoral artery wall and hemostatic factors, and whether these factors were associated with intermittent claudication. One hundred and thirty men at high cardiovascular risk and 51 men at low risk were examined. The subjects (high- and low-risk) with moderate/large plaque (n = 96) had higher fibrinogen, thrombin/antithrombin complex and von Willebrand factor, compared to subjects with small/no plaque. The maximum intima-media thickness of the femoral artery was significantly associated with fibrinogen. These associations were independent of current smoking habits. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex, plasminogen activator inhibitor activity, mean and maximum intima-media thickness and plaque status of the femoral artery. In conclusion, fibrinogen, von Willebrand factor and thrombin/antithrombin complex were related to plaque occurrence in the femoral artery. Clinical atherosclerosis was associated with fibrinogen, von Willebrand factor, thrombin/antithrombin complex and plasminogen activator inhibitor activity.

Intima-media thickness after cholesterol lowering in familial hypercholesterolemia. A three-year ultrasound study of common carotid and femoral arteries.

Patients with familial hypercholesterolemia (FH) (n = 53) were examined with B-mode ultrasound before and after 3 years of cholesterol-lowering therapy with pravastatin, cholestyramine, or a combination. The aim was to measure the progression rate of intima-media thickening during follow-up in the common carotid and common femoral arteries. Since for ethical reasons it was not possible to perform a randomized placebo controlled study in patients with FH, we chose to recruit an untreated control group with lower risk, matched for sex, age, height and weight, and with serum cholesterol below 6.5 mmol/l. At baseline, intima-media thickness was larger in the hypercholesterolemic group than in the control group in both the common carotid and common femoral arteries. The difference between the change over 3 years observed in the control group and the change observed in the hypercholesterolemic group was calculated and defined as 'net difference'. There was a -32% net difference in low density lipoprotein (LDL) in the hypercholesterolemic group during follow-up. The ultrasound investigation showed a concomitant net difference of -0.06 mm in mean carotid intima-media thickness (95% confidence interval, -0.11 to -0.01 mm) and of -0.09 mm in maximum carotid intima-media thickness (P < 0.05, 95% confidence interval, -0.16 to -0.01 mm), with no net change in lumen diameter. No decrease was recorded in common femoral intima-medial thickness. Seventeen of the patients with FH had a positive history of myocardial infarction (MI) and this subgroup had a significantly larger decrease in mean carotid intima-media thickness during follow-up than the subgroup of patients with a negative history of MI (P < 0.01). In conclusion, the results showed a reduction in common carotid intima-media thickness after long-term cholesterol-lowering therapy in patients with FH. This finding may indicate a beneficial effect on atherosclerosis development in these patients.

Carotid artery wall intima-media thickness is associated with insulin-mediated glucose disposal in men at high and low coronary risk.

BACKGROUND AND PURPOSE: The aim of this investigation was to examine the relationship between insulin sensitivity and intima-media thickness in the common carotid artery. METHODS: Ultrasound examinations of the common carotid artery and hyperinsulinemic euglycemic clamp examinations were performed in a group (n = 25) of men aged 57 to 77 years at high risk for atherosclerotic disease (hypertension and at least one of the following factors: hypercholesterolemia and/or smoking) and in an age-matched low-risk group (n = 23) with no cardiovascular risk factors. Subjects with cardiovascular disease or diabetes mellitus were excluded. RESULTS: A significant negative relationship between insulin sensitivity index and common carotid maximum intima-media thickness was observed in both the high-risk group (r = -.45, P < .05) and in the low-risk group (r = -.59, P < .01). CONCLUSIONS: Our results suggest that an increase in intimamedia thickness, as a possible expression of early atherosclerosis, is negatively related to insulin sensitivity.

Ultrasound evaluation of atherosclerotic manifestations in the carotid artery in high-risk hypertensive patients. Risk Intervention Study (RIS) Group.

The aim of this study was to evaluate whether high-risk hypertensive patients (n = 137) had larger far-wall common carotid artery intima-media thickness than a control group (n = 37) and to study whether intima-media thickness was related to other signs of atherosclerotic disease. The results showed that intima-media thickness was significantly larger in the hypertension group than in the control group. Lumen diameter and mean cross-sectional area of the intima-media complex were larger both for hypertensive patients with a positive history of manifest clinical cardiovascular disease and for hypertensive patients with no such history than in the control group. There was a significant relationship between far-wall common carotid artery intima-media thickness and plaque status (visual scoring, no, small, moderate/large) in the carotid artery region. In univariate analyses, low diastolic blood pressure and high pulse pressure were both significantly related to plaque status. In multivariate analyses, pulse pressure was significantly and independently related both to common carotid artery intima-media thickness and to plaque status in the carotid artery region. In multivariate analyses, there was also an independent relationship between age and common carotid artery intima-media thickness, between smoking status and plaque status, and between a positive history of manifest clinical cardiovascular disease and plaque status. In conclusion, common carotid artery intima-media thickness and lumen diameter were increased in elderly high-risk hypertensive patients, in whom more than one third of the patients also had a moderate to large plaque in the carotid artery region.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherosclerotic changes in the femoral and carotid arteries in familial hypercholesterolemia. Ultrasonographic assessment of intima-media thickness and plaque occurrence.

B-mode ultrasound is increasingly used in clinical research to study the atherosclerotic process in the carotid arteries. The present investigation evaluated the feasibility of measuring intima-media thickness in the common femoral artery and assessed whether such measurement might provide further information on the extent of the atherosclerotic process in patients with familial hypercholesterolemia. A further aim was to study the relationship between the intima-media thickness of the common carotid artery and the occurrence of plaque in the carotid and femoral arteries. The results showed an increased intima-media thickness in the far wall of the common femoral artery in patients with familial hypercholesterolemia compared with the control subjects (P < .01). The results also showed a clear relationship between the thickness of the intima-media complex in the common carotid artery and the prevalence of plaque in the carotid and femoral arteries. This may be interpreted as an indication that an increase in intima-media thickness in the common carotid artery at least partly expresses a generalized atherosclerotic process. The atherosclerotic changes appeared to be more advanced in the femoral artery compared with the carotid artery. In future studies, therefore, valuable information on different stages of atherosclerotic changes may be achieved by combining information from B-mode recordings from both the carotid and femoral arteries.

Withdrawal of antihypertensive drug treatment: time-course for redevelopment of hypertension and effects upon left ventricular mass.

OBJECTIVES: To examine: (1) in how many treated hypertensive patients it was possible to discontinue drug treatment; (2) the time-course for redevelopment of hypertension after discontinuation of therapy; and (3) whether drug withdrawal was associated with an increase in left ventricular mass (LVM). DESIGN: Fifty-four men with primary hypertension treated for a mean period of 6 years (primarily beta 1-selective beta-blockade) were evaluated for withdrawal of treatment. Exclusion criteria were signs of organ damage, severe hypertension, other serious disease and unwillingness. Treatment was reinstituted if blood pressure increased above a safety level or if symptoms occurred. Echocardiographic estimations of LVM were obtained before withdrawal and 1, 4 and 8 weeks after withdrawal or before return to treatment. SETTING: Outpatient clinic in a city hospital. PATIENTS: A random sample of 56-year-old hypertensive men. INTERVENTION: Gradual discontinuation of treatment with close follow-up of blood pressure. MAIN OUTCOME MEASURES: Number of patients who could withdraw from treatment and who had to return to pharmacological therapy; time-courses for development of hypertension; absolute changes in LVM. RESULTS: Thirty-two patients withdrew from treatment for 1-1000 days. Therapy was reinstituted in all owing to hypertension or symptoms. Serial echocardiograms were obtained in 22 patients. During the drug-free period, relative wall thickness increased, but LVM did not. Patients with rapid redevelopment of hypertension had larger prewithdrawal LVM than patients whose blood pressure increased more slowly. CONCLUSION: It was possible to withdraw treatment and obtain readable echocardiograms in a minority of the patients. After drug-withdrawal, relative wall thickness increased, but not LVM. We suggest that previously treated patients should be avoided in studies examining reversal of left ventricular hypertrophy.

Arterial wall thickness in familial hypercholesterolemia. Ultrasound measurement of intima-media thickness in the common carotid artery.

B-mode ultrasound was used to noninvasively determine wall thickness and lumen diameter in the common carotid artery in patients with familial hypercholesterolemia (n = 53) and in a control group (n = 53). The controls were matched for sex, age, height, and weight, and all had a serum cholesterol level below 6.5 mmol/l. The study was performed to evaluate whether the patients had a thicker arterial wall compared with that of the control group. Wall thickness was determined as the combined intima-media thickness of the far wall and is presented as the mean and maximum thickness of a 10-mm-long section of the common carotid artery. The difference between the groups was 0.13 mm in mean wall thickness (p less than 0.001; 95% confidence interval, 0.07-0.18 mm) and 0.20 mm in maximum wall thickness (p less than 0.001; 95% confidence interval, 0.09-0.23 mm). Fifty of the subjects were examined twice to estimate the interobserver variability. The coefficients of variation for mean and maximum wall thickness were 10.2% and 8.9%, respectively. The two study groups were well matched and differed only in lipid levels. Thus, there is reason to believe that the difference in wall thickness can be explained by the background of familial hypercholesterolemia and the increased cholesterol levels.