Unfavorable Effects of Passive Smoking on Aortic Function in Men

  1. Christodoulos Stefanadis, MD;
  2. Charalambos Vlachopoulos, MD;
  3. Eleftherios Tsiamis, MD;
  4. Leonidas Diamantopoulos, MD;
  5. Konstantinos Toutouzas, MD;
  6. Nikos Giatrakos, MD;
  7. Sophia Vaina, MD;
  8. Dorothea Tsekoura, MD; and
  9. Pavlos Toutouzas, MD
  1. From Hippokration Hospital, University of Athens, Athens, Greece. Grant Support: By a grant from the Hellenic Heart Foundation. Requests for Reprints: Christodoulos Stefanadis, MD, 9 Tepeleniou str., Paleo Psychico, Athens 154 52, Greece. Current Author Addresses: Dr. Stefanadis: 9 Tepeleniou str., Paleo Psychico, Athens 154 52, Greece.
     
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    Abstract

    Background: The aorta acts as both a conduit and an elastic buffering chamber that modulates left ventricular function and coronary blood flow. Previous studies have shown that active smoking has unfavorable effects on aortic elasticity.

    Objective: To study the association between passive smoking and the elastic properties of the human aorta.

    Design: Comparison of nonsmokers during passive smoking studies and smokers during active smoking or sham smoking studies.

    Setting: Academic medical center.

    Participants: 16 male nonsmokers were assigned to passive smoking studies, and 32 current, long-term, male smokers were randomly assigned to either active smoking (16 patients) or sham smoking (16 patients) studies.

    Intervention: All participants underwent diagnostic catheterization. In the passive smoking group, environmental tobacco smoke was vented into an exposure chamber for 5 minutes (mean carbon monoxide level, 30 parts per million). Each participant in the active smoking group smoked one filtered cigarette (1.0 mg of nicotine) under standardized conditions within 5 minutes; each participant in the sham smoking group performed a similar pattern of inhalation with one unlit cigarette.

    Measurements: Aortic elastic properties were studied by measuring the aortic pressure-diameter relation before and for 20 minutes after passive, active, or sham smoking. Instantaneous diameter of the thoracic aorta was measured with a high-fidelity ultrasonic dimension catheter. Instantaneous aortic pressure and diameter were measured at the same site.

    Results: Both passive and active smoking were associated with changes in the aortic pressure-diameter relation (change in mean distensibility in the passive smoking group, from 2.02 to 1.59 × 10−6 cm2 · dyne−1 [for comparisons of time course between passive and sham smoking groups, P < 0.001]; change in mean distensibility in the active smoking group, from 2.08 to 1.51 × 10−6 cm2 · dyne (−1) [for comparisons of time course between active and sham smoking groups, P < 0.001]). These changes represent decreases of 21% and 27%, respectively. No changes in aortic elasticity were seen in the sham smoking group.

    Conclusions: Both passive and active smoking are associated with an acute deterioration in the elastic properties of the aorta. This association between exposure to tobacco smoke and aortic elasticity indicates that aortic function deteriorates during passive or active smoking.

    Among other underlying mechanisms, tobacco smoke's effect on the mechanical properties of the arterial wall may play an important role in its catastrophic cardiovascular effects. Previous studies have shown that active smoking influences endothelium-mediated vascular control [1-3], induces coronary artery vasoconstriction [4-7], and increases the stiffness of both muscular and elastic arteries [8-11]. Other investigators have demonstrated that passive smoking is associated with dose-related impairment of endothelium-dependent dilatation and with coronary artery vasoconstriction [12, 13].

    The aorta acts as both a conduit and an elastic buffering chamber. By virtue of its elastic properties, this vessel influences left ventricular performance and coronary blood flow [14-23]. Conceivably, any adverse effect of smoking on aortic performance could compromise left ventricular function and coronary blood flow. Previous studies from our laboratory have shown that aortic elastic properties deteriorate acutely during active smoking [24]. In the current study, we investigated aortic elastic properties during passive smoking by using a high-fidelity method suitable for determining the association between aortic pressure and diameter [24-26].

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    Methods

    Study Group

    Potential participants were male patients who underwent diagnostic cardiac catheterization for evaluation of chest pain. Patients with left main-vessel or three-vessel coronary artery disease, arterial hypertension, valvular heart disease, congenital heart disease, left ventricular systolic dysfunction, chronic obstructive pulmonary disease, history of cerebrovascular accident, and diabetes mellitus were excluded from the study. According to these criteria, 16 nonsmokers and 32 current, long-term smokers (≥ 1 pack per day for ≥ 1 year) were enrolled in the study. The nonsmokers were assigned to passive smoking studies, and the smokers were randomly assigned to either active (16 patients) or sham (16 patients) smoking studies. Cardiovascular agents were withheld for at least five half-lives before the study. The institutional ethical committee approved the study protocol, and each patient provided written informed consent.

    Study Protocol

    Design

    The participants did not consume caffeine-containing beverages or meals and refrained from smoking for at least 12 hours before the study. Diagnostic cardiac catheterization and studies of aortic performance were performed during the same catheterization session. After diagnostic catheterization, the participants were allowed to relax in the supine position. An exposure chamber was placed over the heads of the persons in the passive smoking group. Thirty minutes after the last infusion of contrast medium, baseline hemodynamic measurements were obtained. For the passive smoking group, environmental tobacco smoke was then vented into the exposure chamber for 5 minutes; an average carbon monoxide level of 30 parts per million was maintained. The exposure chamber was subsequently removed and patients were allowed to inhale smoke-free room air. Carbon monoxide levels were measured by using a portable carbon monoxide analyzer (Model T15, Langan Products, San Francisco, California).

    After baseline measurements, the participants in the active smoking group each smoked one filtered cigarette containing 1.0 mg of nicotine under standardized conditions: Every 15 seconds, a puff lasting 5 seconds was taken, and the whole cigarette had to be smoked within 5 minutes. The participants in the sham smoking group performed a similar pattern of inhalation with one unlit cigarette. All variables except cardiac output were measured at baseline and at 1, 2, 3, 4, 5, 10, 15, and 20 minutes after the initiation of passive, active, or sham smoking. Cardiac output was measured by thermodilution at baseline and at 5, 10, and 20 minutes after initiation of passive, active, or sham smoking.

    Measurement of Aortic Diameters and Pressures

    Instantaneous aortic diameters were measured at the descending thoracic aorta by a Y-shaped intravascular catheter that was developed in our laboratory and uses sonometry to measure diameter (Figure 1). Aortic pressures were obtained simultaneously at the same point of the aorta by a 3-French catheter-tip micromanometer (Model SPC-330, Millar Instruments, Houston, Texas), as described elsewhere [24-26].

    Figure 1. Diameter-measuring device and cathetertip micromanometer are positioned at the same point of the thoracic aorta.
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      Figure 1. Diameter-measuring device and cathetertip micromanometer are positioned at the same point of the thoracic aorta. Study instruments.

      Data Acquisition

      A VF-1 mainframe (Crystal Biotech, Hopkinton, Massachusetts) was fitted with appropriate modules for measuring aortic diameter and pressure and acquiring an electrocardiogram. Signals were digitized every 5 milliseconds. The digitized data were stored and processed by using Microsoft Excel software (Redmond, Washington).

      Estimation of Aortic Elastic Properties and Pressure-Diameter Relation

      The slope of the pressure-diameter loop and aortic distensibility were used as measures of aortic elasticity [24-31].

      Statistical Analysis

      Slope of the Pressure-Diameter Loop

      The aortic pressure-diameter loop is derived by plotting digitized data for the pressure (ordinate) and the diameter (abscissa) during a single cardiac cycle (Figure 2). The line of this plot during cardiac systole is not identical to the line during cardiac diastole because diameter lags behind pressure as a result of the viscoelastic nature of the aortic wall. Thus, this plot assumes the shape of a clockwise hysteretic loop, the ascending portion of which corresponds to systole and the descending portion of which corresponds to diastole. Multiple loops were obtained for all participants during the study. To characterize the loop, linear regression analysis of pressure versus diameter was done separately in each loop to determine the slope (that is, the regression coefficient b of the following regression equation: pressure = α + b x diameter) of the regression line. The slope of this regression line (DeltaP/DeltaD) is an index of aortic elasticity because it gives an inverse measure of the changes in aortic diameter that occur during the cardiac cycle as a response to the changes in distending pressure. With a given change in aortic pressure, a vessel with deteriorated elastic properties responds with a relatively small change in aortic diameter (thus, the slope of the pressure-diameter regression line will be high). In contrast, with a given change in aortic pressure, a vessel with improved elastic properties responds with a relatively large change in aortic diameter (thus, the slope of the pressure-diameter regression line will be low).

      Figure 2. Loops were obtained before and 4 minutes after the initiation of passive smoking for the participant in the passive smoking group ( ), before and 5 minutes after the initiation of active smoking for the participant in the active smoking group ( ), and before and 5 minutes after the initiation of sham smoking for the participant in the sham smoking group ( ). At baseline, 0.028 (1/35.465 [that is, 1/slope]) is the change in diameter (mm) per unit change in pressure (mm Hg). This measure of elasticity decreased to 0.017 (1/57.91) in the fourth minute of passive smoking. Moreover, the loop shifted to another hypothetical line of elasticity. Similar loop behavior was seen in all passive smokers and in the active smoking group. Five minutes after sham smoking began, the loop remained practically the same. (Regression lines are derived from one participant and one cardiac cycle; arrows indicate the regression lines to which the equations correspond).
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        Figure 2. Loops were obtained before and 4 minutes after the initiation of passive smoking for the participant in the passive smoking group ( ), before and 5 minutes after the initiation of active smoking for the participant in the active smoking group ( ), and before and 5 minutes after the initiation of sham smoking for the participant in the sham smoking group ( ). At baseline, 0.028 (1/35.465 [that is, 1/slope]) is the change in diameter (mm) per unit change in pressure (mm Hg). This measure of elasticity decreased to 0.017 (1/57.91) in the fourth minute of passive smoking. Moreover, the loop shifted to another hypothetical line of elasticity. Similar loop behavior was seen in all passive smokers and in the active smoking group. Five minutes after sham smoking began, the loop remained practically the same. (Regression lines are derived from one participant and one cardiac cycle; arrows indicate the regression lines to which the equations correspond). Representative examples of pressure-diameter loops of three participants (one each from the passive, active, and sham smoking groups).topmiddlebottom

        The pressure-diameter loop operates along a hypothetical line of elasticity. Shifting of the pressure-diameter loop to a different hypothetical line of elasticity provides valuable information on the mechanisms involved in the changes in aortic elastic properties (Figure 3).

        Figure 3. Passive changes in aortic elastic properties are related to changes in blood pressure alone and are characterized by sliding of the pressure (P)-diameter (D) loop along the same hypothetical sigmoid line of elasticity. Active changes in elastic properties are related to changes in intrinsic elastic properties and are characterized by the shifting of the pressure-diameter loop to the left or right of the initial hypothetical sigmoid line of elasticity. If this shifting is associated with a counterclockwise rotation of the pressure-diameter loop, the new hypothetical line of elasticity has a steeper slope, denoting reduced elastic properties. Reproduced from Stefanadis and colleagues with permission.
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          Figure 3. Passive changes in aortic elastic properties are related to changes in blood pressure alone and are characterized by sliding of the pressure (P)-diameter (D) loop along the same hypothetical sigmoid line of elasticity. Active changes in elastic properties are related to changes in intrinsic elastic properties and are characterized by the shifting of the pressure-diameter loop to the left or right of the initial hypothetical sigmoid line of elasticity. If this shifting is associated with a counterclockwise rotation of the pressure-diameter loop, the new hypothetical line of elasticity has a steeper slope, denoting reduced elastic properties. Reproduced from Stefanadis and colleagues with permission. Left.Right.[24]

          Aortic Distensibility

          Aortic distensibility was calculated from the following formula: Distensibility = 2Deltad/(d x DeltaP) × 10−6 cm2 · dyne−1, where d is diastolic aortic diameter, Deltad is the difference between the systolic and diastolic aortic diameters (pulsatile change in aortic diameter), and DeltaP is the difference between the systolic and diastolic aortic pressures (pulse pressure).

          Large distensibility values represent improved aortic elastic properties, and small values represent deteriorated properties.

          Data Analysis

          To obtain individual patient values of aortic pressure and diameter and derived variables at every time point, as well as values of the slope of the pressure-diameter loop regression line, analyses were done on 10 consecutive heartbeats and results were averaged. No values were missing for any variable at any time point. Data are expressed as the mean ±SD. Repeated-measures analysis of variance (averaged F) was used to detect statistically significant changes in variables within the groups (passive, active, and sham smoking) during the study period, to compare these variables between the passive and sham smoking groups and between the active and sham smoking groups, and to determine whether the time course of these variables differed between the passive and sham smoking groups and between the active and sham smoking groups. To test the univariate homogeneity of variance between the passive and sham smoking groups and between the active and sham smoking groups, the Cochran and Bartlett-Box tests were used. The Box M test was used to assess the equality of the variance-covariance matrices. Greenhouse-Geisser ε correction was used in the repeated-measures analysis of variance when the Box M test was significant [32]. Normality assumptions, tested by using the Kolmogorov-Smirnoff one-sample test and by calculating the ratio of skewness to the SE of skewness of the sample distribution, were satisfied. P values less than 0.05 were considered statistically significant. Data analysis was done with SPS software, version 7.0 (Chicago, Illinois).

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          Results

          Baseline Characteristics

          Three participants in the passive smoking group, three in the active smoking group, and four in the sham smoking group had angiographically normal coronary arteries; the remaining participants had coronary artery disease. Age, baseline hemodynamic measures, and baseline aortic elasticity measures in the three groups are shown in Table 1.

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          Table 1. Baseline Characteristics of the Study Groups*

          Changes after Passive Smoking

          Heart Rate, Cardiac Function, and Aortic Pressures

          Passive smoking was associated with prompt increments in the mean heart rate; cardiac index; and systolic, diastolic, and pulse pressures. Most of these increments occurred during the first 5 minutes. The mean heart rate and cardiac index increased over time in the passive smoking group (peaks at 5 minutes, 76 beats/min [P < 0.001] and 3.6 L/min · m−2 [P = 0.001]; Table 2) and remained the same with sham smoking (P > 0.2 for both variables). These variables were similar in the passive and sham smoking groups (P = 0.2 for heart rate and P = 0.24 for cardiac index), but their time course differed between the two groups (P < 0.001 for heart rate and P = 0.002 for cardiac index). In both the passive and the sham smoking group, the systemic vascular resistance index did not change with time (P > 0.2 for both comparisons [Table 2]). This variable and its time course were similar in the passive and sham smoking groups (P > 0.2 for both variables).

          View this table:
          Table 2. P Values for Repeated-Measures Analysis of Variance within and between Groups

          The mean systolic and diastolic aortic pressures increased with passive smoking over time (peak at 4 minutes, 145.8 mm Hg for systolic pressure and 83.7 mm Hg for diastolic pressure; P < 0.001 for both variables [Figure 4 and Table 2]) and remained the same with sham smoking (P > 0.2 for both variables). Moreover, although the mean systolic and diastolic pressures were similar in the two groups (P = 0.1 for systolic pressure and P > 0.2 for diastolic pressure), both variables increased more rapidly in the passive smoking group (P < 0.001 for both variables). The mean pulse pressure increased over time in the passive smoking group (peak at 4 minutes, 62.1 mm Hg; P = 0.005 [Table 2]) and remained the same in the sham smoking group (P > 0.2). Although this variable was similar in the passive and sham smoking groups (P = 0.2), it increased more rapidly in the passive smoking group (P = 0.004).

          Figure 4. values correspond to comparisons of the time course of these variables (the fifth column of for passive compared with sham smoking and the sixth column of for active compared with sham smoking). Error bars represent SDs.
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            Figure 4. values correspond to comparisons of the time course of these variables (the fifth column of for passive compared with sham smoking and the sixth column of for active compared with sham smoking). Error bars represent SDs. Mean systolic and diastolic aortic pressure before, during, and after passive smoking (top), sham smoking (middle), and active smoking (bottom).PTable 2Table 2

            Aortic Diameters

            The mean systolic and diastolic aortic diameters during the study are shown in Figure 5. Both diameters increased with passive smoking over time (peak at 4 minutes, 23.98 mm for systolic diameter [P = 0.04] and 22.53 mm for diastolic diameter [P = 0.001]; Table 2) and remained the same with sham smoking (systolic diameter, P > 0.2; diastolic diameter, P = 0.2). Although these variables were similar in the passive and sham smoking groups (P > 0.2 for systolic and diastolic), the time course of diastolic diameter differed in these groups (P = 0.01) and the difference in the time course of systolic diameter was marginally insignificant (P = 0.06). Passive smoking was associated with a decrease in pulsatile change in aortic diameter over time (minimum, 1.43 mm at 5 minutes; P = 0.002 [Table 2]); in the sham smoking group, the pulsatile change remained the same (P > 0.2). This variable was similar in the passive and sham smoking groups (P = 0.2) but decreased more rapidly in the passive smoking group (P = 0.03). The clinical significance of the changes in aortic diameter seen with passive smoking can only be inferred by their contribution to the changes in aortic elasticity indexes described later in this article and by explanations of the mechanisms involved in these changes.

            Figure 5. values correspond to comparisons of the time course of these variables (the fifth column of for passive compared with sham smoking and the sixth column of for active compared with sham smoking). Error bars represent SDs.
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              Figure 5. values correspond to comparisons of the time course of these variables (the fifth column of for passive compared with sham smoking and the sixth column of for active compared with sham smoking). Error bars represent SDs. Mean diastolic and systolic aortic diameter before, during, and after passive smoking (top), sham smoking (middle), and active smoking (bottom).PTable 2Table 2

              Aortic Pressure-Diameter Relation

              The values of the slope of the aortic pressure-diameter relation (slope of the pressure diameter loops [Figure 2]) averaged over time were higher in the passive smoking group than in the sham smoking group (P = 0.02 [Table 2]), indicating reduced elastic properties in the passive smoking group. Passive smoking was also associated with an increase in the average slope of the aortic pressure-diameter relation over time (P < 0.001), a finding that suggests reduced elastic properties. In contrast, the slope remained the same in the sham smoking group (P > 0.2). Thus, the average change in diameter per unit change in pressure decreased in the passive smoking group from 0.029 (1/34.83 [that is, 1/slope]) to a minimum of 0.022 (1/44.86) at 4 minutes of passive smoking (22% decrease); the diameter also remained lower compared with the baseline diameter (data not shown). In addition, the mean slope increased more rapidly in the passive smoking group than in the sham smoking group (P < 0.001).

              Figure 2 shows the pressure-diameter loops in the passive smoking group; these loops are not indicative of the group's mean changes in variables but were selected to illustrate loop behavior. The pressure-diameter loop shifted to another hypothetical line of elasticity (Figure 3). Similar shifting of the pressure-diameter loop to another hypothetical line of elasticity was seen in all participants in the passive smoking group. In contrast, the pressure-diameter loop did not shift in the sham smoking group (Figure 2).

              Aortic Distensibility

              The values of distensibility, averaged over time, were lower in the passive smoking group than in the sham smoking group (P = 0.04 [Figure 6 and Table 2]). Although average distensibility decreased over time in the passive smoking group (from 2.02 to a minimum of 1.59 × 10−6 cm2 · dyne−1 at 4 minutes [21% decrease]; P < 0.001), indicating reduction of aortic elastic properties, it remained the same in the sham smoking group (P > 0.2). Moreover, mean distensibility decreased more rapidly in the passive smoking group than in the sham smoking group (P < 0.001).

              Figure 6. values correspond to comparisons of the time course of this variable (the fifth column of for passive compared with sham smoking and the sixth column of for active compared with sham smoking). Error bars represent SDs.
              View larger version:
                Figure 6. values correspond to comparisons of the time course of this variable (the fifth column of for passive compared with sham smoking and the sixth column of for active compared with sham smoking). Error bars represent SDs. Mean aortic distensibility before, during, and after passive smoking (top), sham smoking (middle), and active smoking (bottom).PTable 2Table 2

                Changes after Active Smoking

                Active smoking was associated with prompt increments in mean heart rate, cardiac index, and systolic and diastolic aortic pressures. Most of these increments were seen during the first 5 minutes of smoking. Figure 4 shows the mean systolic and diastolic aortic pressures during the study. Over time, mean heart rate (P < 0.001), cardiac index (P < 0.001), systolic blood pressure (P = 0.001), and diastolic blood pressure (P < 0.001) increased with active smoking (Table 2). These variables were similar in the active and sham smoking groups (heart rate, P = 0.1; cardiac index, P > 0.2; systolic pressure, P > 0.2; diastolic pressure, P > 0.2); however, the time course of these variables differed between the two groups (P < 0.001 for heart rate, cardiac index, and diastolic pressure; P = 0.001 for systolic pressure). Mean systemic vascular resistance index, pulse pressure, and systolic and diastolic diameters did not show statistically significant differences for all tests (for P values, see Table 2). The mean systolic and diastolic aortic diameters during the study are shown in Figure 5. Mean pulsatile change in aortic diameter decreased over time (P < 0.001; Table 2). This variable differed between the active and sham smoking groups (P < 0.001) and decreased more rapidly in the active smoking group than in the sham smoking group (P < 0.001).

                The mean slope of the pressure-diameter relation and aortic distensibility (Figure 6) changed with active smoking over time; this finding suggests deterioration of aortic elastic properties (P < 0.001 for both comparisons [Table 2]). These variables differed between the active and sham smoking groups (slope, P < 0.001; distensibility, P = 0.003). Moreover, these variables changed more rapidly in the active smoking group than in the passive smoking group (P < 0.001 for both comparisons). In all participants in the active smoking group, the pressure-diameter loop shifted to another hypothetical line of elasticity (Figure 2).

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                Discussion

                Our study shows that passive smoking is associated with an unfavorable acute deterioration of aortic elastic properties. This finding was evident promptly after the initiation of passive smoking and was maintained for at least 20 minutes.

                Smoking and Arterial Mechanical Properties

                Coronary and Large Arteries

                The effect of cigarette smoking on vascular control may contribute to the many unfavorable health consequences of smoking. Active smoking causes immediate constriction of epicardial coronary arteries and increases coronary resistance vessel tone [4-7]. Moreover, it affects endothelium-mediated vascular control in clinically healthy persons [1-3]. Other investigators [8] have shown an acute deterioration of the mechanical properties of both the elastic common carotid artery and the muscular brachial artery after active smoking; a transitory increase in stiffness of radial and femoral arteries has also been shown [9-11]. In addition, passive smoking has been associated with dose-related impairment of endothelium-dependent dilatation in healthy adults and with mild coronary artery vasoconstriction in nonsmoking adults [12, 13].

                Aorta

                By showing that passive smoking has a similar unfavorable effect on aortic elastic properties, our current study extends the findings from our previous studies that have shown an acute deterioration in the elastic properties of the human aorta with active smoking [24]. Behavior of the pressure-diameter relation provides valuable information about the mechanisms involved in these changes. Estimation of aortic elastic properties is based on the expansion of aortic diameter in response to distending pressure. This relation is essentially linear: The greater the increase in distending pressure (from diastolic to systolic pressure), the greater the change in aortic diameter (from diastolic to systolic diameter); the pressure-diameter loop operates on the linear part of a hypothetical line of elasticity (Figure 3). Beyond a certain point, however, this relation is no longer linear: The hypothetical line of elasticity assumes a steeper slope, and larger changes in distending pressure lead to relatively smaller changes in aortic diameter (reduced deltaD/deltaP [inverse slope]). If the intrinsic properties of the aortic wall do not change, changes in blood pressure alone (which are called passive changes in aortic elastic properties) are characterized by the sliding of the pressure-diameter loop upward or downward along the same hypothetical line of elasticity. On the other hand, changes of the intrinsic aortic elastic properties (which are called active changes in the elastic properties of the vessel) are characterized by shifting of the pressure-diameter loop to the left or right of the initial hypothetical line of elasticity. Thus, the pressure-diameter loop operates on a different line of elasticity that has a steeper slope if the intrinsic elastic properties of the vessel have deteriorated [24-2629, 33, 34]. With respect to our findings for passive smoking, the aorta was distended at first (hence the increase in systolic and diastolic diameter) because of the elevation in blood pressure (passive change); this finding is consistent with those of previous studies of active smoking in other elastic-type arteries, such as the carotid artery [8]. Moreover, the shift of the pressure-diameter loop in another hypothetical line of [deteriorated, as indicated by the steeper slope] elasticity with passive or active smoking suggested the contribution of an active mechanism in these changes. Thus, the deterioration of aortic elastic properties was the net effect of the combination of two different mechanisms: 1) the passive distention of the aorta due to an increase in blood pressure and 2) the active stiffening of the vessel due to elevated muscular tone, in response to both passive and active smoking.

                Smooth-muscle cells are the arterial-wall components that are subject to acute and active changes. Both active and passive smoking affect endothelium-mediated vascular control in clinically healthy persons [1-3, 12]. Active stiffening of the vessel caused by elevated muscular tone may be related to activation of the sympathetic nervous system [35, 36]. Other pharmacologic effects of active or passive smoking that may affect aortic tone include inhibition of prostacyclin production by endothelial cells [37], activation of platelets [38], and release of vasopressin [39]. Smooth-muscle cell function may also be affected by impaired nutrition of the aortic wall because of possible direct vasoconstriction of the vasa vasorum or impaired flow due to the increase in blood pressure [31].

                Clinical Implications

                Heart disease is an important consequence of exposure to environmental tobacco smoke. The unfavorable effects of passive smoking on aortic function may have important clinical implications, particularly through the resulting compromised performance of the left ventricle and disturbance in the balance of myocardial supply and demand. The potential applicability to large populations and the considerable duration of these effects throughout the day further stress the clinical significance of our findings.

                Left Ventricular Performance

                Aortic elastic properties are an important component of left ventricular afterload and constitute a major determinant of left ventricular power output [14-17]. Thus, passive smoking negatively affects left ventricular performance by stiffening the aorta. The importance of this influence may be more prominent in patients with left ventricular dysfunction or disease states, such as coronary artery disease or hypertension, in which aortic distensibility is already affected [18, 25-3040, 41].

                Myocardial Oxygen: Supply and Demand

                Exposure to tobacco smoke increases myocardial oxygen demand [2, 4, 5, 7-935, 42-45]. It also concomitantly reduces supply by causing direct vasoconstriction in the coronary bed [4-713, 44, 45]. Moreover, as our current findings indicate, coronary perfusion may be compromised with smoking because of an additional mechanism: Deterioration of aortic elastic properties adversely influences coronary flow [18-20]. It is conceivable that, when exposed to tobacco smoke, the left ventricle is forced to function under the deleterious combination of increased oxygen demand and decreased oxygen supply for a considerable period during the day.

                Study Limitations

                Both passive and active smoking caused an increase in heart rate and cardiac output. These changes may have contributed to the deterioration of aortic elastic properties and may represent an indirect mechanism by which exposure to tobacco smoke influences aortic elasticity. Several additional limitations of study deserve mention. All participants were men, most of whom had coronary artery disease. Thus, we can only speculate about whether aortic function in other groups, such as women or persons without coronary artery disease, responds similarly to tobacco smoke exposure. In addition, the aorta becomes stiffer with advancing age [25, 34]. It is reasonable to speculate that our findings may be applicable to populations older than the one that we studied. However, these findings may be more prominent in younger populations, especially children, in which a more elastic aorta has the “reserve” to deteriorate; an aorta stiffened by age may not have this reserve.

                Conclusions

                We show that both passive and active smoking are associated with an acute deterioration in aortic elastic properties. This change becomes evident soon after the initiation of passive or active smoking and is maintained for at least 20 minutes. This association between exposure to tobacco smoke and aortic elasticity indicates that aortic function deteriorates during passive or active smoking.

                Drs. Vlachopoulos, Tsiamis, Diamantopoulos, Toutouzas, Giatrakos, Vaina, Tsekoura, and Toutouzas: Department of Cardiology, Athens Medical School, Hippokration Hospital, 114 Vassilissis Sophias Avenue, Athens 11527, Greece.

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                1. Ann Intern Med March 15, 1998 vol. 128 no. 6 426-434
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