|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2000; 35:673-680 © 2000 by the American College of Cardiology Foundation |
* Centre d’Investigations Préventives et Cliniques (IPC), Paris, France
INSERM U337, Paris, France
INSERM U258, Villejuif, France
Manuscript received May 3, 1999; revised manuscript received September 26, 1999, accepted November 10, 1999.
Reprint requests and correspondence: Dr. Athanase Benetos, Centre d’Investigations Préventives et Cliniques (IPC), 6-14 rue de la Perouse, 75116 Paris, France
 |
Abstract |
|---|
 Top Abstract MethodsResultsDiscussionDiastolic BP and cardiovascular...References |
|---|
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.
| ||||||||||||||||||||||||
Thus, although high systolic BP usually reflects an elevation in total peripheral resistance and/or large artery stiffness, diastolic BP levels are influenced by arterial or arteriolar alterations in opposite ways: an increase in peripheral vascular resistance leads to an elevation in diastolic BP, whereas stiffening of large arteries can induce a decrease in diastolic BP (5,6). Therefore, normal levels of diastolic BP are influenced by the combination of these two vascular alterations, which are both independent risk factors of cardiovascular disease, especially coronary artery disease (7,8). This leads to the conclusion that levels of diastolic BP may not necessarily reflect cardiovascular risk, especially in older subjects among whom arterial stiffness is more frequent.
Long-term longitudinal changes in BP may be a more accurate determinant of BP-related risk; this is because changes in systolic BP or diastolic BP over a period of time reflect the evolution of arterial and arteriolar alterations. Witteman et al. (9) showed that, in women, a decrease in diastolic BP during a nine-year follow-up was associated with a progression of atherosclerotic lesions of the aorta. The investigators suggested that the decrease of diastolic BP could be a marker of atherosclerosis.
To our knowledge, there are no epidemiological data showing the effect of spontaneous (non-treatment-related) changes of systolic and diastolic BP over an extended period of time, on cardiovascular mortality. The present analysis was performed in two independent French male cohorts: the IPC (Investigations Préventives et Cliniques) cohort, consisting of 15,561 males who had had two visits spaced four to 10 years apart at the "IPC" Centre, and the Paris Prospective Study I, consisting of 6,246 men who had had an annual medical exam over a four-year period. The associations between combined changes in systolic BP and diastolic BP over this period were studied, and subsequent cardiovascular mortality was also assessed (a mean period of 13.5 years for the IPC Study and 17 years for the Paris Prospective Study, beginning after the last visit).
|
Methods |
|---|
|
TopAbstractMethodsResultsDiscussionDiastolic BP and cardiovascular...References |
|---|
Supine BP was measured in the right arm by a nurse, using a manual sphygmomanometer. After a 10-min rest period, BP was measured three times and the mean of the last two measurements was calculated. Family medical history (diabetes, hypertension, cardiovascular disease and sudden death before 60 years), personal drug regimen and tobacco consumption were assessed using a self-administered questionnaire. Blood samples for biological tests were drawn under fasting conditions.
The follow-up study period ended in December 1996. The minimum follow-up period after the second visit was 5 years, the maximum was 17 years, and the mean follow-up period was 13.5 years. Deceased subjects were identified from the mortality records at the Institut National de Statistiques et d’Etudes Economiques (INSEE). A patient from our cohort was classified as deceased when he had the same first name, last name, gender and date of birth as a person recorded in the INSEE mortality records during the period of the follow-up. By using this matching procedure, the identification error was less than 1%. Only subjects meeting all four of these criteria were classified as deceased. All other subjects were considered to be alive at the end of the follow-up period. Following this procedure, 874 subjects from our cohort were classified as having died during the follow-up period. Causes of mortality were taken from the death certificates. These data were provided by the Department of Mortality (SC 8) at the National Institute of Health and Medical Research (INSERM). Causes of death were codified according to the International Classification of Disease (8th revision until 1978, 9th revision thereafter).
Paris Prospective Study I
Details pertaining to recruitment, design, and procedures of the Paris Prospective Study I have been described elsewhere (10). Briefly, the first examination (baseline) for 7,746 French policemen aged 43 to 52 years was carried out between 1967 and 1972. Subjects had a physical examination, provided blood samples for laboratory tests and answered questionnaires administered by trained interviewers, regarding sociodemographic factors, medical history and smoking habits. Each year following the baseline examination and up to four years after, all subjects were invited to undergo a similar follow-up examination. The number of participants per cohort who had one, two, three, four, or five examinations was 614, 604, 601, 1,671 and 4,456, respectively. During each examination, BP was measured in the sitting position after at least a 5-min rest, and the mean of two measurements was used for the analysis. Through inquiries made to hospitals, family physicians and medical services at work, men were followed up until January 1, 1994. Date and place of death were also noted, and the medical causes of death were obtained from death certificates from INSERM, in the same manner as for the IPC cohort. Of the 7,332 subjects who had at least two examinations, the vital status after an average follow-up of 17 years after the last examination was obtained for 6,892 subjects (94%). In the present study, we included all subjects of this cohort who did not receive antihypertensive treatment and for whom complete clinical and mortality data were obtained.
BP change calculation.
The IPC Study
Individual annual changes in systolic BP and in diastolic BP were calculated as the difference between the second and the baseline value, divided by the time between the two visits. Mean time delay between the first and the second visit was 6.1 ± 1.7 years. Blood pressure increased significantly over time in the entire population (0.2 ± 2.5 and 0.2 ± 2.0 mm Hg per year for systolic BP and diastolic BP, respectively, p < 0.001 for each). Annual changes in systolic BP and in diastolic BP were regressed on baseline values, and residuals were divided into tertiles. For systolic BP, the lowest tertile (i.e., a decrease [
] in systolic BP) included men whose systolic BP fell by >5.4 mm Hg per five years; the highest tertile (i.e., an increase [
] in systolic BP) included those whose systolic BP increased by >3 mm Hg per five years; and the intermediate tertile was considered as a lack of change (
) in systolic BP. The respective cutoff points for tertiles for diastolic BP changes were –2 mm Hg and +3 mm Hg per five years. Nine groups of subjects were formed by combining the changes of systolic BP and diastolic BP between the two visits.
Paris Prospective Study I
Changes in systolic BP and in diastolic BP from the first through the last (fifth or less) examination were estimated using a within-person linear regression method. Systolic BP and diastolic BP were regressed onto calendar time. On the average, systolic BP increased and diastolic BP significantly decreased over time in the entire population (0.2 ± 5.2 mm Hg per year; p = 0.004 and –0.5 ± 4.0 mm Hg per year; p < 0.001, respectively). The resulting annual average systolic BP and diastolic BP changes (regression slopes) were then regressed on baseline values, and residuals were divided into tertiles. The cutoff points for tertiles were –10.6 and +5.9 mm Hg per five years for changes in systolic BP and –6.7 and +5.4 mm Hg per five years for changes in diastolic BP. The final sample consisted of 6,246 subjects who were not treated for hypertension and for whom complete data were available.
Statistical analysis
Data from each cohort were analyzed separately. Death rates for the different causes of mortality, according to the systolic BP/diastolic BP-change groups, were compared using a 
2 test, and differences in survival probability were tested using log-rank test. A Cox multivariate analysis evaluated risks of cardiovascular mortality adjusted for baseline age, total cholesterol, tobacco consumption, diabetes and body mass index (BMI). Because initial BP levels were taken into account in the calculation of BP changes and the formation of the different groups, adjustment for BP was not necessary. The group SysDia (lack of change in both systolic BP and diastolic BP between the two visits) was considered as the reference group. All statistical analyses were performed using SAS software.
|
Results |
|---|
|
TopAbstractMethodsResultsDiscussionDiastolic BP and cardiovascular...References |
|---|
|
|
(decrease in systolic BP), 7.7 per 10,000 person-years in the Sys (no change in systolic BP) and 15.5 per 10,000 person-years in the Sys (increase in systolic BP). According to the diastolic BP changes, mortality rates were 9.6, 6.8 and 13.7 deaths per 10,000 person-years, respectively.
According to the combined changes of both systolic BP and diastolic BP, the analysis in all nine groups showed that the SysDia (increase in systolic and decrease in diastolic BP) group presented the highest rates for total cardiovascular mortality (24.4 deaths per 10,000 person-years) (Table 2). The Cox regression showed that after adjustment for age alone or age and other risk factors, the SysDia group was the only group to present a significantly higher risk of cardiovascular mortality compared to the reference group (SysDia [no change in systolic and no change in diastolic BP]) (Table 3). Analyses performed separately (according to the mean value of age,—that is, 42 years) showed that the higher risk in the SysDia group was observed in both younger and older subjects. Change in pulse pressure was also a significant determinant of cardiovascular mortality in this cohort. After adjustment for age and other risk factors, the risk ratio related to a 10 mm Hg increase in pulse pressure was 1.9 (1.0 to 3.5) (p < 0.05).
|
Dia group was not related to an early mortality. This analysis showed that the increased mortality in the SysDia group, compared to the reference group (SysDia), clearly appeared after the fourth year of the follow-up period and persisted up to the end of follow-up (p = 0.012) (Fig. 1, upper panel). Figure 1 also shows that in the groups with a decrease in diastolic BP, without an increase in systolic BP, the survival curve was not different from the reference group. Finally, in groups with an increase in systolic BP and without a decrease in diastolic BP, the survival curve showed intermediate values between the reference group and the SysDia group.
|
, 37.4 per 10,000 person-years in the Sys, and 57.1 per 10,000 person-years in the Sys. According to the diastolic BP changes, these rates were 41.8, 38.5 and 53.5, respectively.
|
Dia group (65.4 deaths per 10,000 person-years, Table 4).
The relative risks for death from cardiovascular disease are shown in Table 3. The age-adjusted relative risk for subjects in the SysDia group, compared with those in the SysDia group, was 2.14 [95% CI 1.15–3.96]. Multivariate adjustment for baseline risk factor levels did not alter these findings. These results were very similar to those observed in the IPC Study (Table 3). As for the IPC cohort, analyses performed according to the mean value of age (47 years) showed that a higher risk of cardiovascular mortality in the SysDia group was observed in both younger and older subjects. Subjects in the SysDia (increase in systolic and increase in diastolic BP) group were also at higher risk compared with those in the SysDia group.
As also observed for the IPC study, change in pulse pressure was a significant determinant of cardiovascular mortality in this cohort. After adjustment for age and other risk factors, the risk ratio (95% CI) related to a 10 mm Hg increase in pulse pressure was 1.7 (1.4–2.1) (p < 0.001.).
The study of the survival curves for cardiovascular mortality in the Paris Prospective Study indicated similar trends to those observed in the IPC Study (Fig. 1, lower panel).
|
Discussion |
|---|
|
TopAbstractMethodsResultsDiscussionDiastolic BP and cardiovascular...References |
|---|
Cardiovascular mortality according to systolic and diastolic BP changes in two French cohorts.
In the present report, two independent French cohorts were analyzed separately. As is shown in the Results section, subjects enrolled in the Paris Prospective Study had much higher mortality rates compared to subjects in the IPC Study. The differences in mortality can be explained in part by the fact that the subjects from the Paris Prospective Study were older (mean age 47.1 vs. 41.9 years old) and that the follow-up period was longer (17 vs. 13.5 years). However, the main reason for this difference could be that the prevalence of risk factors, especially tobacco consumption, was much higher in the Paris Prospective Study (see Table 1). This cohort was composed of policemen, enrolled in the study between 1967 and 1972, and constituted a population that was very exposed to risk factors. The fact remains that despite these major differences, the following noteworthy result was found in both cohorts: subjects with the SysDia profile presented a higher cardiovascular risk, a risk that was twice as high as for the reference population (SysDia).
Following the classification in tertiles according to the progression of systolic BP and diastolic BP, the higher cardiovascular death rates were observed in the Sys tertile. This is not really surprising as this tertile had the higher systolic BP levels during the second visit (i.e., at the beginning of the follow-up period). Inside this tertile, one would expect higher mortality rates in the subgroup, which had the higher systolic BP and diastolic BP levels at the time of the last visit. If we consider the subjects from the IPC study, average BP values in the SysDia group were 141/76 mm Hg during the last visit. In the SysDia and SysDia groups the corresponding levels of BP were 141/82 mm Hg and 149/94 mm Hg, respectively. Based on this logic, patients in the SysDia group should present the highest cardiovascular mortality compared to the other groups. However, in the present study, the higher cardiovascular mortality rates were observed among subjects in the SysDia group. This excess risk is independent of absolute BP levels measured during single visits, and therefore can be determined only if the evolution of BP over an extended period of time is taken into consideration.
|
Diastolic BP and cardiovascular risk |
|---|
|
TopAbstractMethodsResultsDiscussionDiastolic BP and cardiovascular...References |
|---|
In addition, Cox et al. (14) pointed out that this relationship has been found in both normotensive individuals and in hypertensive patients receiving placebos. In a detailed review of the subject, Fletcher and Bulpitt (15) raised the question of whether or not low diastolic BP in patients with isolated systolic hypertension predisposes that group to the risk because of the increased myocardial needs due to associated high systolic BP levels. The results of the present analysis concur with this hypothesis, showing that a decrease in diastolic BP (non–drug-related in this case) was harmful only when it was combined with an elevation in systolic BP. On the contrary, when a decrease in diastolic BP was accompanied with a concomitant decrease or lack of change in systolic BP, cardiovascular risk did not increase (Fig. 1).
Pulse pressure and cardiovascular risk. It has recently been shown that increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality, independently of mean BP levels (16–18). The present results point out that the increase of systolic and pulse pressure over time is probably due to an increase in aortic stiffness and pulse-wave velocity and to accentuation of the amplitude of the reflected pressure waves (5). We believe that the present study helps clarify the role played by arterial stiffening in cardiovascular complications. The present results demonstrate the risk related to the increase in pulse pressure due to both an increase in systolic BP and a decrease in diastolic BP, which is the classic pattern of large arteries stiffening. We can therefore suggest that other causes leading to elevated pulse pressure, such as increased stroke volume, may be considered less harmful. The study emphasizes that the impact of systolic and pulse pressure is not only observed in the elderly but also in a middle-aged population sample.
Clinical applications. Therapeutic decision-making and management in patients with mild to moderate hypertension are based on the evaluation of cardiovascular risk. Clinicians therefore have sought more precise ways of describing individual patient outlooks. One of the problems when treating for hypertension is that very large numbers of subjects have to be treated to prevent a small number of cardiovascular complications (19). This suggests that the standard criteria, systolic BP or diastolic BP, even if they are generally correlated to cardiovascular risk, may not be specific or sensitive enough to identify groups of subjects that are at high risk owing to BP values. In the present analysis we identified a subgroup of subjects, representing approximately 3% of the total population, whose excess in risk was independent of BP recorded during single visits, age and other risk factors.
In the present study the same hypothesis was tested separately in two independent French cohorts. Because the Paris Prospective Study was composed only of men, only the male population in the IPC cohort was analyzed. Results of the present study may be of interest to clinicians for several reasons. In the case of normal or slightly increased BP levels, when treatment does not need to be proposed, long-term follow-up of BP levels may help estimate an individual’s cardiovascular risk and contribute to therapeutic decision making. In subjects with high BP, for whom physicians should propose a first treatment, comparison with older BP readings when available could contribute to a better estimation of cardiovascular risk.
In conclusion, assessment of spontaneous BP changes over a long period of time may contribute to the evaluation of cardiovascular risk. Subjects who present a combined increase in systolic BP and a decrease in diastolic BP have the highest risk, independently of absolute BP values and other risk factors.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMethodsResultsDiscussionDiastolic BP and cardiovascular...References |
|---|
This article has been cited by other articles:
|
|
 |
|
  Authors/Task Force Members:, G. Mancia, G. De Backer, A. Dominiczak, R. Cifkova, R. Fagard, G. Germano, G. Grassi, A. M. Heagerty, S. E. Kjeldsen, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) Eur. Heart J., June 11, 2007; (2007) ehm236v1. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aronson, M. L. Fontes, Y. Miao, D. T. Mangano, and for the Investigators of the Multicenter Study of Risk Index for Perioperative Renal Dysfunction/Failure: Critical Dependence on Pulse Pressure Hypertension Circulation, February 13, 2007; 115(6): 733 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fernandez-Fresnedo, E. Rodrigo, A. L. M. de Francisco, S. S. de Castro, O. Castaneda, and M. Arias Role of Pulse Pressure on Cardiovascular Risk in Chronic Kidney Disease Patients J. Am. Soc. Nephrol., December 1, 2006; 17(12_suppl_3): S246 - S249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Senti, J. M. Fernandez-Fernandez, M. Tomas, E. Vazquez, R. Elosua, J. Marrugat, and M. A. Valverde Protective Effect of the KCNMB1 E65K Genetic Polymorphism Against Diastolic Hypertension in Aging Women and Its Relevance to Cardiovascular Risk Circ. Res., December 9, 2005; 97(12): 1360 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benetos Does Blood Pressure Control Contribute to a More Successful Aging? Hypertension, August 1, 2005; 46(2): 261 - 262. [Full Text] [PDF]
|
|
|
|
|
|
M. Zureik, P. Galan, S. Bertrais, D. Courbon, S. Czernichow, J. Blacher, P. Ducimetiere, M. E. Safar, and S. Hercberg Parental Longevity and 7-Year Changes in Blood Pressures in Adult Offspring Hypertension, August 1, 2005; 46(2): 287 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Safar, M. Lajemi, A. Rudnichi, R. Asmar, and A. Benetos Angiotensin-Converting Enzyme D/I Gene Polymorphism and Age-Related Changes in Pulse Pressure in Subjects with Hypertension Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 782 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. G. Lakatta and D. Levy Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: Part I: Aging Arteries: A "Set Up" for Vascular Disease Circulation, January 7, 2003; 107(1): 139 - 146. [Full Text] [PDF]
|
|
|
|
 |
|
 J.-J. Mourad, G. Ducailar, A. Rudnicki, M. Lajemi, A. Mimran, and M. E Safar Age-related increase of pulse pressure and gene polymorphisms in essential hypertension: a preliminary study Journal of Renin-Angiotensin-Aldosterone System, June 1, 2002; 3(2): 109 - 115. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Aronson, D. Boisvert, and W. Lapp Isolated Systolic Hypertension Is Associated with Adverse Outcomes from Coronary Artery Bypass Grafting Surgery Anesth. Analg., May 1, 2002; 94(5): 1079 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benetos, F. Thomas, K. Bean, S. Gautier, H. Smulyan, and L. Guize Prognostic Value of Systolic and Diastolic Blood Pressure in Treated Hypertensive Men Arch Intern Med, March 11, 2002; 162(5): 577 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Blacher and M. Safar Specific aspects of high blood pressure in the elderly Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1_suppl): S10 - S15. [PDF]
|
|
|
|
|
|
L. M.A.B. Van Bortel, H. A.J. Struijker-Boudier, and M. E. Safar Pulse Pressure, Arterial Stiffness, and Drug Treatment of Hypertension Hypertension, October 1, 2001; 38(4): 914 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. Mourad, J. Blacher, P. Blin, and U. Warzocha Conventional Antihypertensive Drug Therapy Does Not Prevent the Increase of Pulse Pressure With Age Hypertension, October 1, 2001; 38(4): 958 - 961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Aviv Hypothesis : Pulse Pressure and Human Longevity Hypertension, April 1, 2001; 37(4): 1060 - 1066. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benetos, F. Thomas, M. E. Safar, K. E. Bean, and L. Guize Should diastolic and systolic blood pressure be considered for cardiovascular risk evaluation: a study in middle-aged men and women J. Am. Coll. Cardiol., January 1, 2001; 37(1): 163 - 168. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
