L. Guize

Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality

Studies on the prognostic significance of blood pressure on cardiovascular disease have essentially investigated the levels of diastolic or systolic blood pressure. However, blood pressure may also be divided into two other components: steady (mean arterial pressure) and pulsatile (pulse arterial pressure). The relations of these two components with cardiovascular risk factors and cardiovascular mortality were investigated in 18,336 men and 9,351 women aged 40-69 years, who were followed up for a mean period of 9.5 years. However, the interpretation of the relations is complicated by the strong correlation existing between these two components. A principal component analysis was performed to obtain two independent parameters: a steady and a pulsatile component index, strongly correlated with mean and pulse arterial pressure, respectively. In the cross-sectional analysis, relations were stronger with the steady component index than with the pulsatile component index; an association was found between left ventricular hypertrophy and the pulsatile component index in both sexes. The survival analysis was not performed in women under 55 as only 11 cardiovascular deaths occurred in this group. The steady component index was a strong prognostic factor of all types of cardiovascular death in both sexes. In women, the pulsatile component index was positively correlated to death from coronary artery disease and inversely correlated to stroke. In conclusion, the steady component of blood pressure is a strong risk factor for cardiovascular death in both sexes; the pulsatile component could be a risk factor independent of the steady component in women older than 55 years.

Pulse Pressure and Cardiovascular Mortality in Normotensive and Hypertensive Subjects

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.

Risk factors for early carotid atherosclerosis in middle-aged French women.

The prevalence of carotid atherosclerosis and of its risk factors was examined in 517 apparently healthy French women, aged 45-54 years. Early phases of carotid atherosclerosis were assessed by B-mode ultrasonography. An intimal-medial thickening was found in 30.4% of the women and atheromatous plaques in 8.7%. The prevalence rate of carotid atherosclerosis increased with age, smoking, and postmenopausal status. However, after adjustment for the effect of age, postmenopausal women did not have more atherosclerotic lesions than did premenopausal women. No significant associations were found between carotid atherosclerosis and triglyceride, apolipoprotein A-I, body mass index, blood glucose, fibrinogen, plasma viscosity, or hematocrit. The mean age-adjusted levels of total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, and systolic and diastolic blood pressures significantly increased with the severity of carotid atherosclerosis, whereas high density lipoprotein cholesterol significantly decreased. Multiple regression analysis showed that age, smoking, high density lipoprotein cholesterol, low density lipoprotein cholesterol (or apolipoprotein B), and systolic (or diastolic) blood pressure were significantly and independently related to the severity of carotid atherosclerosis. In conclusion, the association of early carotid lesions with major cardiovascular risk factors suggests that carotid atherosclerosis may be used as a marker of the general atherosclerotic process.

A Decrease in Diastolic Blood Pressure Combined With an Increase in Systolic Blood Pressure Is Associated With a Higher Cardiovascular Mortality in Men

OBJECTIVES The study evaluated the risk of cardiovascular mortality according to combined spontaneous (non-treatment-related) changes in both systolic and diastolic blood pressure (BP). BACKGROUND Long-term longitudinal changes in blood pressure may be a more accurate determinant of cardiovascular risk since changes in systolic or diastolic blood pressure over a period of time reflect the evolution of arterial and arteriolar alterations. METHODS Two independent French male cohorts were studied: the IPC cohort (Investigations Préventives et Cliniques) composed of 15,561 men aged 20 to 82 years who had had two visits spaced four to 10 years apart, and the Paris Prospective Study composed of 6,246 men aged 42 to 53 years, examined annually for a period of four years. None of the subjects were taking antihypertensive medication. Annual changes in BP were estimated, and subjects were divided into groups according to the increase, lack of change, or decrease of systolic or diastolic BP. Nine groups were formed by combining the changes of systolic and diastolic BP. Cardiovascular mortality was assessed for a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospective Study. RESULTS In both cohorts, after adjustment for age and major risk factors, the group with an increase in systolic and a decrease in diastolic BP presented the highest relative risk of cardiovascular mortality compared to the group with no changes in either systolic or diastolic BP (relative risk: 2.07 [1.05 to 4.06] in the IPC Study and 2.16 [1.16 to 4.01] in the Paris Prospective Study). CONCLUSIONS Assessment of spontaneous changes of BP over a long period of time can contribute to the evaluation of cardiovascular risk. Subjects whose systolic BP increased while their diastolic BP decreased had the highest cardiovascular risk independently of absolute values of BP or other risk factors.

Inhomogeneity of cellular refractoriness in human atrium: factor of arrhythmia?

Spatial inhomogeneity of refractory periods, as measured during clinical electrophysiological studies, is a known predisposing factor of arrhythmia. We studied elective refractory periods (ERP) and action potential duration (ADP90) on isolated human atrium. Twelve samples of right atrium obtained during cardiac surgery from patients with (n = 6) and without (n = 6) atrial fibrillation (AF) were studied by microelectrode technique. For each preparation, ERP were measured at basic cycle lengths (BCL) of 1,600, 1,200, 800, and 400 msec in five different cells located around (0.8 mm) the stimulating electrode. Dispersion of ERP was significantly greater in the AF group (96.7 ± 9 versus 70.9 ± 9 msec, p = 0.01). In the non‐AF group, we observed a positive linear correlation between (1) ERP and BCL (f = 0.86) (2) ADP90 and BCL (r̄= 0.93). On the contrary, in the AF group this correlation was absent between ERP and BCL (r̄= 0.28), poor between ADP90 and BCL (r̄= 0.62). These results suggest that nonhomogeneous recovery of excitability (dispersion and poor adaptation) may be an important factor of arrhythmia. This inhomogeneity is present at the cellular level as well as in the entire heart.

Population Correlates of Coagulation Factor VII Importance of Age, Sex, and Menopausal Status as Determinants of Activated Factor VII

Factor VII coagulant activity (FVIIc) has been found to be related to cardiovascular risk factors and may be an independent predictor of coronary heart disease (CHD). Whether these associations are due to changes in FVII activation rather than FVII concentration remain unclear. Therefore, we investigated the relationships between activated factor VII (FVIIa) and CHD risk factors in healthy subjects (336 men and 348 women) aged 25 to 64 years. In addition to direct quantitation of FVIIa by use of a recombinant, truncated tissue factor, FVIIc and factor VII antigen (FVII:Ag) levels were measured by standard procedures. There were highly significant correlations between the three techniques of FVII assay (r > + .55). Plasma FVIIc and FVIIa levels increased with age in both sexes, but the rate of rise was significantly greater in women than men. At younger ages, mean values of FVIIc and FVIIa were significantly lower in women than men, whereas at older ages the reverse was observed. After adjustment for age, postmenopausal women had significantly higher mean levels of FVIIc and FVIIa than did premenopausal women. Hormone replacement therapy significantly reversed the rise in FVIIc in postmenopausal women, and a similar trend in FVIIa was also observed. Age-, sex-, and menopause-related changes in FVIIc were partly explained by a higher proportion of fully active FVII molecules, as indicated by significant differences in the FVIIa-to-FVII:Ag ratio. Oral contraceptive use was associated with high FVIIc levels, and this effect was mainly due to an increase in FVII:Ag. Levels of FVIIa were positively correlated with serum cholesterol concentrations in both sexes. There were no strong associations between FVIIa levels and other CHD risk factors, including smoking habits, alcohol consumption, blood pressure, obesity, glucose, triglycerides, and serum lipoprotein(a) concentrations. Multiple regression analysis showed independent effects of age and cholesterol levels on FVIIa in men, whereas age and menopausal status were the main predictors of FVIIa in women. Our results show that FVII activation is associated with CHD risk factors. These findings are consistent with a possible role for FVII in the pathogenesis of CHD. Furthermore, our data suggest that the dramatic rise in CHD incidence in postmenopausal women as well as the cardioprotective effect of estrogen may be mediated through FVII and blood coagulation.

Correlation Between Time‐Domain Measures of Heart Rate Variability and Scatterplots in Postinfarction Patients

Heart rate variability (HRV) is usually measured in time or frequency domains. Beat‐to‐beat variability, which cannot be assessed by frequency‐domain analysis, and can only be assessed globally by time‐domain analysis, provides information concerning the nonlinear behavior of heart rate. This beat‐to‐beat variability can be displayed on Scatterplots, where each RR interval is plotted against the preceding RR interval. However, the relationship between Scatterplots and other measures of HRV is unknown. We studied the correlations between time‐domain measures and scatterplot length, width, and area in 50 postinfarction patients. Scatterplot length and width were measured after printing. Scatterplot area was calculated from length and width, assimilating the plot to an ellipse. Long‐term variability indexes (SDNN and SDANN) were strongly correlated with scatterplot length (r > 0.9, P < 0.0001), and short‐term variability parameters (pNN50 and variability index) with scatterplot width (r > 0.9; P < 0.0001). Scatterplots are, therefore, a simple way of providing information concerning long‐ and short‐term HRV. Furthermore, measurement of scatterplot width at different given RR intervals could be an approach to the evaluation of short‐term HRV for different heart rates. This could provide a simple way of assessing cardiac parasympathetic modulation at different heart rates.

Early carotid atherosclerosis in healthy middle-aged women. A follow-up study.

Background and Purpose Few longitudinal data about early atherosclerotic lesions of the carotid arteries are available in general populations. The main purpose of this study was to investigate risk factors for development and regression of intimal-medial thickening and atheromatous plaques. Methods Initial and 2-year examinations of the carotid arteries with high-resolution B-mode ultrasonography were performed in 308 apparently healthy women aged 45 to 55 years. The development of new atheromatous plaques and new intimal-medial thickening and the disappearance of preexisting plaques and intimal-medial thickening defined the four outcomes of interest. Results The development of plaques occurred more frequently in women with intimal-medial thickening than in women with normal carotid arteries at baseline (14.4% versus 7.2%, P<.053). A regression was seen in 21.7% of the women with preexisting plaques. Development of intimal-medial thickening occurred in 47.5% of the women with normal carotid arteries whereas 20.2% of the women with preexisting intimal-medial thickening showed a regression of their lesions. Multiple logistic regression showed that smoking (regression coefficient ±SE: 1.281 ±0.450; P<.005), baseline levels of systolic blood pressure (regression coefficient ±SE: 0.031 ±0.015; P<.04) and apolipoprotein B (regression coefficient ±SE: 0.016±0.007; P<.03) were independently associated with the development of plaques, whereas the presence of an intimal-medial thickening did not reach the significance level (regression coefficient ±SE: 0.639±0.436; P<.15). Independent predictors of the development of intimal-medial thickening were age (regression coefficient ±SE: 0.124±0.058; P<.04) and, with a borderline significance level, (log)triglyc-erides (regression coefficient ±SE: 0.854±0.451; P<.06). Low levels of low-density lipoprotein cholesterol (regression coefficient ±SE: 0.027±0.009; P<.004) were associated with its regression. Conclusions This longitudinal study emphasizes the interest of B-mode ultrasonography in the monitoring of early carotid lesions. It gives further support to the hypothesis that intimal-medial thickening may be an early indicator of the atherosclerotic process.

Reproducibility of the ventricular synchronization parameters assessed by multiharmonic phase analysis of radionuclide angiography in the normal heart.

Radionuclide angiography (RNA) permits analysis of contractility and conduction abnormalities. We determined the parameters of normal ventricular synchronization, assessed the reproducibility of the technique, and compared first harmonic (1H) and third harmonic (3H) analysis. Forty-four normal subjects (28 men and 16 women) were studied. RNA was performed in left anterior oblique (LAO) and left lateral (LL) projections. The onset (To), mean time (Tm), total contraction time (Tt) for right ventricle (RV) and left ventricle (LV), interventricular time (TRV−LV = TmLV − TmRV) in LAO, and the apex-to-base time (Ta−b) in LL were measured on the histograms of the time–activity curve. Reproducibility (R) was tested by studying 26 consecutive patients with two successive RNAs. RV starts contracting 25 ms before LV (ToRV = 29 ± 37 ms; ToLV = 54 ± 39 ms; mean ± SD) with a 37 ms longer total contraction time. TRV−LV is 3 ± 16 ms. In LL projection, apex and base contract synchronously: Ta−b = 2 ± 16 ms. 3H analysis enlarges all duration parameters (To, Tm and Tt), but does not alter synchronization (ΔTa−b and ΔTRV−LV between 1H and 3H <1%, p = NS). Reproducibility of the duration (TtLV and TtRV) and synchronization parameters (Ta−b and TRV−LV) is high (R ≤ 2.2%). In conclusion, the simultaneous contraction of right and left ventricles and of apex and base can be quantified by RNA phase analysis with high reproducibility. These results, consistent with published electrophysiological data, provide the basis for further non-invasive investigations of ventricular resynchronization in patients with basal electrical or mechanical asynchrony.

Combined effects of blood pressure and body mass index on left ventricular structure in middle-aged males: cross-sectional and 2-year longitudinal results.

Objective: To compare the 2-year longitudinal with the cross-sectional relationships of blood pressure and body mass index with echocardiographic left ventricular measurements in middle-aged males with no history of cardiovascular disease or hypertension. Methods: M-mode echocardiograms of adequate quality were obtained at initial and 2-year follow-up examinations in 177 subjects. Measurements of left ventricular wall thickness and internal dimensions were made, and estimates of left ventricular mass/height were calculated. Longitudinal changes in left ventricular measurements and risk factors were computed as the differences between the follow-up and initial values. Results: Systolic blood pressure (SBP) was significantly associated with left ventricular mass/height and wall thickness in cross-sectional and in longitudinal analyses. Similar results were observed after adjusting for age, body mass index, sport activity and heart rate. Although body mass index was strongly related to left ventricular mass/height, wall thickness and internal dimension in the cross-sectional study, no significant associations were observed between changes in body mass index and in left ventricular measurements. Conclusions: The present study emphasizes the differential effects of spontaneous changes in blood pressure and body mass index on the evolution of the left ventricular mass in middle-aged males. Spontaneous changes in SBP during the 2-year follow-up period were associated with rapid changes in left ventricular structure. The 2-year period might not have been sufficient for body mass index to induce changes in left ventricular structure. The duration and amplitude of body weight changes which entail changes in left ventricular mass remain to be determined by further longitudinal investigations