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(Hypertension. 1996;27:1046-1052.)
© 1996 American Heart Association, Inc.

Articles

Cardiac and Vascular Structural Changes

Prevalence and Relation to Ambulatory Blood Pressure in a Middle-aged General Population in Northern Italy: The Vobarno Study

Maria Lorenza Muiesan; GianFranco Pasini; Massimo Salvetti; Silvia Calebich; Roberto Zulli; Maurizio Castellano; Damiano Rizzoni; Giorgio Bettoni; Angelo Cinelli; Enzo Porteri; Vittorio Corsetti; Enrico Agabiti-Rosei

From Cattedra di Semeiotica e Metodologia Medica, UOP Scienze Mediche, Università di Brescia (M.L.M., M.S., S.C., R.Z., M.C., D.R., G.B., A.C., E.P., E.A.-R.), and the Department of Medicine, Gavardo Hospital (G.P., V.C.), Brescia, Italy.

Correspondence to Prof Enrico Agabiti-Rosei, Cattedra Semeiotica e Metodologia Medica, UOP Scienze Mediche, Università di Brescia, c/o Spedali Civili, 1a Medicina, Brescia 25100, Italy.

	Abstract

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Abstract The aims of this study were to determine the prevalence of structural changes in the carotid arteries and heart and the correlation between these changes and the commonly recognized cardiovascular risk factors in the general population. Structural changes in the carotid arteries were defined as the intima-media thickness of the artery measured by B-mode ultrasound. Changes in the heart were defined as left ventricular mass index (LVMI) measured by echocardiography. LVMI values greater than 134 g/m² in men and greater than 110 g/m² in women were considered abnormal, indicating the presence of left ventricular hypertrophy. Blood pressure (BP) was measured in the clinic setting with a mercury sphygmomanometer and by 24-hour noninvasive ambulatory monitoring. Hypertension was defined as a sustained systolic BP greater than or equal to 160 mm Hg and/or diastolic BP increase greater than or equal to 95 mm Hg. The study population consisted of 225 subjects (107 women and 118 men) 48 to 64 years old. Prevalence of intima-media thickening (intima-media thickness >1 mm) was 11% in normotensive subjects and 44% in hypertensive subjects. The presence of plaque (wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall, usually >2 mm) was observed in 35% of normotensive subjects and 44% of hypertensive subjects. The prevalence of left ventricular hypertrophy was 13% in normotensive subjects and 19% in hypertensive subjects. Intima-media thickness in the common and bifurcation segments of carotid arteries correlated well with LVMI (r=.20 and r=.19, respectively; P<.01). Intima-media thickness and LVMI were both positively related to 24-hour monitored BP (P<.01). However, in the multivariate analysis, body mass index (P=.027), sex (P<.001), and 24-hour mean BP (P=.025) were the most significant determinants of LVMI, whereas carotid artery intima-media thickness was found to be associated best with age (P<.001), cigarette smoking (P=.009), serum cholesterol (P=.025), serum glucose (P=.038), and nighttime systolic BP (P=.006). Logistic regression analysis confirmed the association between the presence of plaque and age (P<.001), nighttime systolic BP (P<.05), and cigarette smoking (P<.05); a negative association between plaque and the decrease in mean systolic BP from daytime to nighttime was also observed (P<.001). In conclusion, in a general population of unselected middle-aged subjects, carotid wall thickness and LVMI were associated with each other and related to 24-hour BP levels although the major determinants of carotid wall and cardiac structure were different.

Key Words: carotid arteries • heart • blood pressure monitoring, ambulatory

	Introduction

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Recent epidemiological studies with noninvasive ultrasound techniques^{1 2 3 4 5 6 7 8 9 10 11 12 13} have reported an association between carotid artery wall thickness (presented as intima-media thickness) and cardiovascular disease risk factors, such as hypercholesterolemia,⁵ age,⁴ diabetes,⁶ and BP.^{7 8 9 10 11 12 13} Indeed, SBP level is considered an important determinant of carotid artery intima-media thickness, at least in the common carotid segment,¹⁴ although the association between carotid atherosclerosis and BP was not confirmed in a population-based study by Salonen and Salonen.¹⁴ Furthermore, LV hypertrophy, even of a mild degree, represents a potent independent risk factor for cardiovascular morbidity and mortality¹⁵ among hypertensive patients and in the general population. The presence of LV hypertrophy seems to parallel the extent of structural changes in the common carotid artery in selected hypertensive and normotensive subjects.^{16 17 18 19}

Despite the abundance of data in the literature on the association between BP level and carotid wall thickness, the "true" effect of daily fluctuations of BP, measured noninvasively by 24-hour monitoring, does not seem to be adequately reported. Also, information on the association between LV hypertrophy and carotid artery intima-media thickness at different BP levels monitored over a 24-hour period seems to be scant.

Thus, we designed a population study to determine the prevalence of carotid artery intima-media thickness and its relationship with LVMI and BP level monitored over a 24-hour period with a noninvasive BP monitoring system. This study was conducted among the general population of a small town (Vobarno) in the Sabbia Valley in Northern Italy. This article reports on the results of this cross-sectional, observational study.

	Methods

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Study Population
A random sample of 369 men and women aged 48 to 65 years (66% of the entire population of that age) was selected from the electoral rolls of Vobarno, Italy, and asked to participate. Between January 1992 and June 1994, 284 subjects gave informed consent to the study and underwent all the laboratory investigations, with a participation rate of 78%. The study protocol was approved by the institutional committee on human research. The current number of cigarettes smoked and duration of smoking; history of myocardial infarction, angina pectoris, and other ischemic heart disease documented by medical records; and history of hypertension and the use of antihypertensive treatment were recorded by means of a self-administered questionnaire that was checked by an interviewer. Fifty-nine subjects were taking drugs (mainly antihypertensive and/or antianginal) and were excluded from subsequent analysis to avoid the effect of treatment.

Obesity was defined according to the National Institutes of Health Consensus Development Panel criteria²⁰ as body mass index greater than 27.8 kg/m² in men and 27.3 kg/m² in women. Blood was drawn on the same day as the 24-hour BP monitoring was performed after subjects had fasted and abstained from smoking for 12 hours. Total serum cholesterol, triglyceride, glucose, and uric acid levels were determined.

Echocardiography
All subjects underwent standard echocardiographic evaluation. In 282 subjects it was possible to record an echocardiogram of good quality with a Sonos 1000 echocardiographic unit (Hewlett-Packard) fitted with a 2.5-MHz transducer. Echocardiographic studies were performed in the morning with the subject in the supine left lateral decubitus position after 30 minutes of rest. Only two physicians were responsible for recording the echocardiograms. Echocardiographic tracings were of good technical quality and were recorded on light-sensitive paper at a paper speed of 50 mm/s. Two-dimensional imaging of the longitudinal parasternal view was checked to avoid angulation of the ultrasonic beam and consequent changes in LV shape. LV internal dimensions and LV posterior wall and interventricular septal thicknesses were measured according to the recommendations of the American Society of Echocardiography.²¹ LV volumes were calculated with the cube formula. LV mass was calculated according to the Penn Convention²² and indexed to body surface area, calculated by the formula of Dubois and Dubois.²³ LV hypertrophy was considered present if the LVMI exceeded 110 g/m² in women and 134 g/m² in men.²⁴ Echocardiographic tracings were calculated blindly by two expert independent readers, and the average measurements were considered. Intraobserver and interobserver coefficients of variation of LVMI measurements in both normotensive and hypertensive subjects were 8.2% and 9.2%, respectively.

Carotid Ultrasound
B-mode imaging of carotid arteries was performed with a Hewlett-Packard Sonos 1000 echocardiographic unit equipped with a 7.5-MHz imaging transducer. Subjects were investigated lying in the supine position with slight hyperextension of the neck, and the common carotid artery, carotid bifurcation, and extracranial portions of the internal and external carotid arteries were identified. The average duration of scanning was 30 minutes. The entire scanning procedure was recorded on half-inch superVHS videotape. All carotid measurements were subsequently performed by two independent readers who were unaware of the subject's identity, echocardiographic measurements, and risk factors, and average values were considered. VCR recordings of the entire scanning were analyzed with the measure morphometry software of the echo unit.

Measurements included end-diastolic (minimum diameter) intima-media thickness of the far walls (the distance from the leading edge of the first echogenic line to the leading edge of the second echogenic line) as described previously by Pignoli et al.¹ Several measures were obtained in each arterial segment (6 to 12) according to previously described protocols,^{25 26 27} and the mean value of all measurements on the far wall for each segment was calculated. Wall thickness was never measured at the site of a discrete plaque. The average intima-media thickness was defined as the average of mean intima-media thicknesses in the six carotid segments examined. Repeated scans were recorded randomly and measured on two different occasions in a group of 20 subjects. Interobserver and intraobserver coefficients of variation for measurements of intima-media thickness were 7.6% and 6.9%, respectively, comparable with those reported by Salonen et al.²⁸

Definitions of early atherosclerotic lesions for studies that use B-mode for imaging of artery walls are variable, and several criteria for defining normal walls, intima-media thickening, and plaque have been proposed.^{3 4 5 9 25 26 27} In the present study, the criteria of Salonen and Salonen³ were applied: a normal wall was considered when intima-media thickness was less than 1 mm; carotid wall thickening was considered when intima-media thickness was greater than 1 mm; and a plaque was considered in the presence of wall thickening with either mineralization or focal protrusion in the lumen at least 50% greater than the surrounding wall (usually >2 mm).

BP Measurements
BP was always measured by the same physician with a mercury sphygmomanometer in the clinic setting. Three measurements were taken with subjects in a sitting position after 10 minutes of rest. The diagnosis of essential hypertension was determined by a sustained increase in SBP greater than or equal to 160 mm Hg and/or DBP greater than or equal to 95 mm Hg according to World Health Organization/International Society of Hypertension guidelines²⁹ and the absence of laboratory and/or clinical findings suggesting secondary forms of hypertension.

Twenty-four-hour BP and heart rate were evaluated by noninvasive automatic monitoring (SpaceLabs model 90207). The interval between two subsequent measurements was 20 minutes from 7 AM to 11 PM and 30 minutes from 11 PM to 7 AM, with a total number of about 64 measurements per day. Subjects were fitted with the recorder at 9 AM; it was removed at 10 AM the following day (25 hours of monitoring). Subjects were allowed to follow their normal daily routine after they left the laboratory and were asked to refrain from heavy physical exercise and to keep a diary indicating their location and the activities of the day. Recordings were not made during weekends or holidays, and shift workers did not undergo ambulatory recording while working at night. Each time a reading was taken, subjects were instructed to remain motionless and record their activity on a diary sheet. Most of the readings were taken as subjects sat. The recorder automatically discarded false readings (eg, arm in motion or sound interference during recording). Furthermore, additional readings were rejected during computer analysis if differential BP was less than 20 mm Hg, DBP was less than 50 mm Hg, or SBP was more than 260 mm Hg in isolated readings. Less than 15% of the total readings were rejected as artifacts. Recordings were included in the study only if at least 85% of the maximal number of 64 readings during the 24-hour period passed the deletion criteria. The following values from the 24-hour BP profiles were calculated: mean 24-hour, daytime, and nighttime SBP and DBP; mean 24-hour pulse pressure; and the absolute difference between mean daytime and nighttime SBP and DBP. Mean BP (DBP plus one third pulse pressure) was calculated by the computer.

Statistical Analysis
Data were stored and analyzed with BMDP statistical software programs 7D, 8D, LR 2R, and 9R (BMDP Statistical Software Inc). All data are expressed as mean±SD. Differences between groups (according to the presence or absence of intima-media thickening and plaque) were analyzed by ANOVA, and significance was calculated with the Tukey test for multiple comparison. The relation between continuous variables was evaluated by linear regression. Stepwise multiple regression analysis was used to select the variables providing the best fitting equation to elucidate the relative importance of the different variables as predictors and potentially as determinants of cardiac and carotid vascular structure; entry into the equations was restricted to variables whose partial F test was significant at a value of P<.05. In addition, the association of intima-media thickening or plaque and of LVMI with BP was investigated by means of logistic regression analysis, taking into account the possible confounding effect of variables such as age, sex, body mass index, cigarette smoking, and serum glucose, cholesterol, triglyceride, and uric acid levels.

	Results

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Study Population
The demographic characteristics of the 225 untreated subjects are shown in Table 1. Twenty-nine men and 25 women were obese; 51 subjects (23%) were current smokers and 17 (8%) were former smokers. Fasting glycemia ranged from 6.1 to 7.8 mmol/L in 17 subjects (7.6%), and none of the subjects was diabetic. Total cholesterol ranged from 5.2 to 6.47 mmol/L in 103 subjects and exceeded 6.47 mmol/L in 63 subjects.

View this table: [in this window] [in a new window]   Table 1. Demographic, Hemodynamic, and Humoral Data on 225 Untreated Subjects in the Vobarno Study Population

In 59 subjects, the diagnosis of hypertension, established in the clinic setting (clinic SBP/DBP: 155±10/96±3 mm Hg in hypertensive subjects and 135±11/83±6 mm Hg in normotensive subjects, P<.0001), was confirmed by 24-hour monitoring (24-hour SBP/DBP: 137±9/87±8 mm Hg in hypertensive subjects and 120±9/75±7 mm Hg in normotensive subjects, P<.0001 for both comparisons). When the presence of white coat hypertension was evaluated according to Pickering et al,³⁰ 9 additional subjects had elevated clinic BP values (SBP/DBP: 152±12/95±5 mm Hg) and "normal" ambulatory values (ie, awake BP <134/90 mm Hg). As previously reported in a larger sample of a general population,³¹ mean 24-hour SBP and DBP values were several millimeters of mercury lower than clinic BP values.

Carotid Artery Structure (Intima-Media Thickness) and Atherosclerosis
The results of the carotid B-mode ultrasound examination are shown in Table 2. Carotid wall thickness was significantly greater in men than in women in all segments explored (common carotid, 0.78±0.25 and 0.68±0.20 mm, P=.002; carotid bifurcation, 1.12±0.49 and 0.95±0.35, P=.003; internal carotid, 0.70±0.49 and 0.59±0.34 mm, P=.048, in men and women, respectively).

View this table: [in this window] [in a new window]   Table 2. Distribution of Intima-Media Thickness in the Common, Bifurcation, and Internal Carotid Artery Segments in the Study Population

Carotid artery wall thickness (measured as both the average intima-media thickness of all sites and the intima-media thickness of the common carotid artery) was less among nonsmokers compared with smokers (0.70±0.21 versus 0.79±0.25 mm and 0.80±0.26 versus 0.93±0.33 mm, respectively; P<.001). The difference in intima-media thickness between smokers and nonsmokers was statistically significant in both men and women.

Carotid artery walls were significantly thicker in hypertensive than in normotensive subjects. This was the case when the thickness of the common carotid segment alone and the average intima-media thickness of all sites were considered (0.79±0.25 versus 0.72±0.25 mm for common carotid artery and 0.93±0.31 versus 0.81±0.29 mm for the average intima-media thickness for all sites measured, P<.01 for both cases).

Intima-media thickness of the common carotid artery and the average intima-media thickness of all sites were related to age (r=.31 and r=.38, respectively; P<.001), 24-hour SBP (r=.18 and r=.19, respectively; P<.01 for both comparisons), nighttime SBP (r=.24 and r=.26, respectively; P<.001 for both comparisons), 24-hour pulse pressure (r=.25 and r=.27, respectively; P<.01 for both comparisons), LVMI (r=.20 and r=.23, respectively; P<.01 for both comparisons), and glycemia (r=.20, P<.01 and r=.15, P=NS, respectively). Common carotid and average intima-media thicknesses were inversely related to the absolute difference between daytime and nighttime SBP means (r=-.22 and r=-.24, respectively; P<.001 for both comparisons).

We performed multivariate regression analysis (Table 3) to determine which factors were independently related to carotid wall intima-media thickness. Age was the strongest predictor for intima-media thickness, as measured in all carotid segments. Other variables independently related to wall thickness were cigarette smoking and mean nighttime SBP. Glycemia was related to common carotid intima-media thickness, and cigarette smoking did not show any relation with intima-media thickness in the internal carotid artery.

View this table: [in this window] [in a new window]   Table 3. Multivariate Relations of Carotid Intima-Media Thickness With Age, Cigarette Smoking, LV Mass Index, Glycemia, and Systolic BP in the Study Population

The entire population was divided according to the presence or absence of atherosclerosis³ : 93 subjects had normal carotid intima-media thickness in all segments (41%); 47 had thickening of the intima-media complex in at least one segment (21%); and in 85 subjects (38%), a plaque (plus intima-media thickening in 52) in at least one segment was observed. Age and serum glucose (ANOVA, P<.0001 and P=.05, respectively) were significantly higher in subjects with thickening of the intima-media alone; and age, male sex, and mean nighttime SBP (ANOVA, P<.05 for all comparisons) were significantly greater in the group of subjects with plaque (Table 4). The difference between daytime and nighttime SBP means was significantly less in subjects with plaque.

View this table: [in this window] [in a new window]   Table 4. Demographic, Hemodynamic, and Humoral Data of 225 Untreated Subjects According to the Presence of a Normal Intima-Media Thickness, Thickening of the Intima-Media Complex, and Plaque

Logistic regression analysis confirmed the association between the presence of plaque and age (P=.001), mean nighttime SBP (P=.015), and cigarette smoking (P=.03); a negative association between plaque and the decrease of mean SBP from daytime to nighttime was also observed (P<.001). The presence of intima-media thickening alone was associated with age (P<.0001), serum cholesterol level (P=.025), and serum glucose level (P=.038).

LV Structure
Echocardiographic values of LV anatomic characteristics are presented in Table 5. LV hypertrophy was present in 21 men and 13 women and in 19% of hypertensive and 13% of normotensive subjects. All subjects were pooled for analysis of the correlation between LVMI and other variables. LVMI was positively related to all 24-hour SBP and DBP means (r=.25 and r=.26, respectively; P<.001), sex (r=-.43, P<.001), body mass index (r=.39, P<.001), and wall thickness in the common carotid (r=.19, P<.01) and bifurcation (r=.19, P<.01).

View this table: [in this window] [in a new window]   Table 5. Echocardiographically Determined LV Mass, LV Mass Index, LV Wall Thickness, and LV End-Diastolic and End-Systolic Dimensions in the Study Population

In the multivariate regression analysis, sex, body mass index, and 24-hour mean BP accounted for a 25% variation in LVMI; separate analysis by sex revealed that LVMI was predicted only by body mass index among women and men. Variables that did not enter the regression model were age, serum glucose level, and cholesterol level (Table 6).

View this table: [in this window] [in a new window]   Table 6. Multivariate Relations of LV Mass Index to Sex, Body Mass Index, and 24-Hour Mean BP in the Study Population

Among subjects with plaque, LVMI was greater although not statistically significant (Table 4); LV hypertrophy was observed in 12 subjects (14%) with normal carotid wall thickness, in 4 subjects (9%) with intima-media thickening, and in 18 subjects (21%) with carotid plaque (ANOVA, P=.012).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
In this study, we attempted to determine the prevalence of structural changes in both the carotid arteries and the heart in apparently healthy, middle-aged men and women living in Vobarno, a small town in northern Italy.

Intima-Media Thickness and LV Mass
The prevalence of structural changes in both carotid arteries and the heart has previously been evaluated in relatively small groups^{16 17 18} and more recently in larger populations^{12 19} of selected normotensive and hypertensive subjects. In these studies, structural changes in the common carotid artery seem to parallel a proportional increase in LV mass.

In our population, intima-media thickness in all carotid segments, except the internal carotid artery, was correlated with LVMI. A reliable estimate of the association between cardiac and vascular carotid structure was obtained in the present study; to what extent prolonged treatment has influenced previous results^{12 18} is not known.

Determinants of LV Mass
As previously described,³² obesity, sex, and BP were the strongest determinants of echocardiographic LVMI.^{33 34} LVMI showed a positive relation with DBP but not SBP levels measured in the clinic. The apparent discordance with results obtained in the Framingham cohort study³⁵ and more recently in an elderly "healthy" population³⁶ could be explained by the younger age of our cohort, the lower prevalence of LV hypertrophy, and the restriction of this analysis to apparently "healthy" subjects. The closer relationship between LVMI and 24-hour monitored BP values in hypertensive subjects^{37 38 39 40} and in normotensive subjects was confirmed in our study population.

Determinants of Carotid Intima-Media Thickness
Hospital-based and population studies^{7 8 28 41 42 43} have established an association between common carotid intima-media thickness and cardiovascular disease risk factors, such as age,⁷ cigarette smoking, total and low-density lipoprotein cholesterol, diabetes,⁶ and BP.^{12 14 42} Ambulatory SBP and pulse pressure means (calculated as the difference of mean SBP and DBP values of 48 measurements per week recorded with a semiautomatic device) have been considered important determinants of maximal intima-media thickness, at least in the common carotid artery.¹⁴ Furthermore, SBP was positively and DBP inversely related to common carotid intima-media thickness in older subjects, probably because of decreasing vascular compliance with advancing age.³⁶ However, in all these studies, in which arterial wall thickness was assessed by B-mode ultrasound according to a protocol comparable with ours, BP was always obtained by office readings. The "true" effect of daily fluctuations of BP on the vessels, assessed noninvasively by 24-hour ambulatory monitoring, has not yet been related to carotid wall thickness. Preliminary results indicate that the relation between carotid wall thickness and BP did not improve when monitored values were considered, with respect to clinic measurements.⁴⁴

In our study, a significant correlation was found between carotid intima-media thickness and monitored SBP. Multivariate regression analysis confirmed that mean nighttime SBP was one of the strongest determinants of intima-media thickness in all carotid artery segments. Therefore, these results emphasize the important role of an increased hemodynamic load and in particular of a reduced nocturnal dip of BP in the determination of carotid wall thickness.

An overestimation of BP values as a consequence of sleep disturbance by intermittent cuff inflation was reasonably ruled out by the subjects' diary, in which the duration and quality of sleep were always carefully reported⁴⁵ ; also, an afternoon nap could not underestimate daytime BP.

Risk Factors for Carotid Atherosclerosis
It has been reported that extracranial carotid atherosclerosis is related to the level of clinic SBP in middle-aged women⁹ and elderly stroke patients¹⁰ as well as to the presence of hypertension in asymptomatic patients^{11 19} and in patients with ischemic heart disease.¹³ Casual SBP and DBP values are increased in the presence of plaques in two different sites (carotid arteries and abdominal aorta).⁴⁶ Luisiani et al⁴⁷ have demonstrated in a large number of patients that the severity of internal carotid plaque is closely correlated with age but not with known duration of hypertension.

In our study, the presence of a carotid plaque, according to the criteria of Salonen and Salonen,³ was associated with high mean SBP during the night. The mechanisms underlying this association are still unclear. Atherosclerotic changes modify arterial functional properties and therefore determine an increase of SBP throughout the 24 hours; however, the possibility cannot be excluded that persistently elevated BP levels (even within normal limits) could participate in the development of atherosclerotic plaque, especially in the bifurcation and internal carotid segments. A more strict association of a greater wall thickness in the common carotid wall and humoral or genetic⁴⁸ factors has been observed in this population.

Previous echographic studies have shown a relation of carotid atherosclerosis and common carotid maximal intima-media thickness with total and low-density lipoprotein cholesterol in a general population.^{5 41} In hypercholesterolemic normotensive patients, only the ratio of total to high-density lipoprotein cholesterol was slightly increased in the presence of plaques in both the aorta and carotids,⁴⁶ whereas in familial hypercholesterolemia, a greater thickness of the common carotid wall has been shown to be associated with a greater intima-media thickness and the presence of plaques in the femoral arteries.⁴⁹

We could confirm the association between intima-media thickening and total cholesterol; it is possible that the absence of cardiovascular disease and diabetes in our subjects, the high prevalence of women, and the relatively low levels of total cholesterol could account for the absence of a significant correlation between carotid plaque and lipid levels, confirming previous findings reported in asymptomatic patients.¹⁹

The association of abnormal glucose metabolism with intima-media thickness⁶ was confirmed in our population, even in the absence of diabetes. Serum glucose concentration was more strongly associated with intima-media thickness in the common carotid segment, supporting the hypothesis that an abnormal glucose metabolism may promote early structural changes and enhance the effect of other risk factors.

In conclusion, this study documents the presence of early carotid and cardiac structural changes in a general population of apparently healthy, middle-aged men and women and evaluates the relation of cardiovascular structure to monitored BP. Carotid wall thickness was related to LVMI, but different influencing factors were found to be associated with the structure of the heart (body mass index and 24-hour BP values) and of the carotid arteries (age, cigarette smoking, nighttime SBP and glucose and cholesterol levels). Although the homogeneity of the study population may limit extrapolation of results to less homogeneous populations, it would seem that therapeutic interventions to prevent or reduce cardiovascular structural changes are not the same when directed to the arterial vessels or to the heart.

	Selected Abbreviations and Acronyms

 

BP = blood pressure DBP = diastolic blood pressure LV = left ventricular LVMI = left ventricular mass index SBP = systolic blood pressure

	Acknowledgments

 
This work was supported in part by a grant from the Lombardy Region Health and Hygiene Department (Regione Lombardia, Settore Sanita' e Igiene), Italy. The authors are grateful to Nemat Borhani, MD, FACC, for his helpful advice and editorial comment. The authors wish to thank the Vobarno Town Council and in particular Andrea Barbiani, the Mayor of Vobarno, for their invaluable help and assistance in recruiting subjects and conducting the study.

Received October 20, 1995; first decision November 22, 1995; accepted February 7, 1996.

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