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(Stroke. 2005;36:1288.)
© 2005 American Heart Association, Inc.

Research Reports

Association of Blood Pressure Indices and Stroke Mortality in Isolated Systolic Hypertension

Furcy Paultre, PhD Lori Mosca, MD, PhD

From the Columbia University, College of Physicians and Surgeons, New York, NY.

Correspondence to Dr Lori Mosca, Columbia University, College of Physicians and Surgeons, PH 10-203, 622 W 168th St, New York, NY 10032. E-mail ljm10{at}columbia.edu

	Abstract

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Background and Purpose— Isolated systolic hypertension (ISH), systolic blood pressure (BP) 160 mm Hg and diastolic BP (DBP) <90 mm Hg, is associated with stroke; however, the correlation between specific BP indices and stroke mortality in ISH is not defined.

Methods— In a pooled analysis of 9 epidemiological studies, we examined whether pulse pressure (PP) was more predictive of stroke mortality than systolic BP (SBP), DBP, or mean BP (MAP) in persons with ISH. Subjects (n=682; 29% male; 77% white; mean age 63.6 years) with ISH, free of cardiovascular disease, and not on antihypertensive drug therapy at baseline were followed a mean of 13.0±7.3 years, and 54 stroke deaths occurred. The relative importance of each BP index was compared by the decrease in the –2 log likelihood (a measure of model agreement with data) because of the addition of 1 or a combination of BP indices to a Cox regression model. Hazards ratios (HRs) for fatal stroke for a 1-SD in BP index were determined.

Results— PP was the best predictor of stroke mortality based on the decrease in the –2 log likelihood (10.65; P=0.001; HR=1.52), followed by SBP (7.19; P=0.007; HR=1.40), DBP (2.76; P=0.10; HR=0.80), or MAP (0.39; P=0.39; HR=1.10). Any combination of BP indices did not exceed a decrease in the –2 log likelihood of 10.72.

Conclusion— These data suggest that in persons with ISH, PP is a better predictor of fatal stroke than SBP, DBP, or MAP.

Key Words: blood pressure • hypertension • stroke

	Introduction

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Isolated systolic hypertension (ISH) is characterized by elevated systolic blood pressure (BP) in the presence of normal diastolic BP (DBP). A number of studies, including the Systolic Hypertension in the Elderly Program (SHEP), have defined ISH as systolic BP (SBP) 160 mm Hg and DBP <90 mm Hg.¹ Prevalence of ISH increases with age and is associated with increased arterial stiffness. Large-artery stiffness increases in middle-aged and elderly persons,² which causes an increase in SBP and a decrease in DBP.³ This results in an increase in pulse pressure (PP; SBP–DBP) and a higher prevalence of ISH in many older individuals.⁴ Epidemiological studies have demonstrated that persons with ISH are at increased risk of stroke.¹ It remains unclear which of the commonly used BP indices best predicts stroke in persons with ISH.

	Methods

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Data were pooled from 9 long-term epidemiological cohort studies based in the United States as described previously.⁵ Individuals were included in this study if at baseline they were 30 years of age, were free of cardiovascular disease, met the criteria for ISH, and were not on antihypertensive drug therapy. Stroke mortality was defined by International Classification of Diseases (ICD) codes 430 to 438, which included hemorrhagic and nonhemorrhagic events. Mean BP (MAP) was approximated by (SBP+2DBP)/3. Cox proportional hazards regression was used to compare the association between BP indices and stroke mortality. The relative importance of BP indices was compared by the decrease in the –2 log likelihood statistic because of the addition of the individual or dual BP indices to the model adjusted for baseline values of age, gender, ethnicity, cigarette smoking, diabetes, cholesterol, and body mass index.⁶

	Results

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At baseline, 682 subjects (29% male; 77% white) with a mean age of 63.6±8.9 years met the criteria for ISH. During a mean follow-up time of 13.0±7.3 years, 54 stroke deaths were observed.

PP was more predictive of stroke mortality than SBP, DBP, or MAP. Decrease in the –2 log likelihood statistic with the addition of a single BP index (df=1) to the model was greater for PP (10.65_(PP); P=0.001) than for SBP (7.19_(SBP); P=0.007), DBP (2.76_(DBP); P=0.10), or MAP (0.39_(MAP); P=0.39; Figure 1). The magnitude of the percent change in risk of hazard of stroke mortality for a 1-SD increase in BP was also greater and more significant for PP (52%; P=0.0002) than for SBP (40%; P=0.004), DBP (–20%; P=0.065), or MAP (10%; P=0.53; Table).

View larger version (16K): [in this window] [in a new window]   Figure 1. Decrease in the –2 log likelihood when a single BP index (PP [P=0.001], SBP [P=0.007], DBP [P=0.10], or MAP [P=0.53]) or a combination of any 2 BP indices (P=0.005) was added to a Cox proportional hazards regression model predicting stroke mortality adjusted for age, gender, ethnicity, cigarette smoking, diabetes, cholesterol, and body mass index.

View this table: [in this window] [in a new window]   Cox Proportional Models Relating Stroke Mortality to BP Indices*

Because all 4 BP indices are linear combinations of each other, 2 can be used additively in a model. The decrease in the –2 log likelihood statistic when any 2 BP indices (ie, SBP–DBP, SBP–PP, SBP–MAP, DBP–PP, DBP–MAP, or PP–MAP) were added to the multivariable Cox model was 10.72_(2BP) (df=2; P=0.005; Figure 1). This is the maximum decrease in the –2 log likelihood statistic attributable to any additive combination of these 4 BP indices. PP alone accounted for 99% (10.65_(PP)/10.72_(2BP)) of the total possible decrease of the –2 log likelihood statistic attributable to any additive combination of BP indices.

We further examined models containing 2 BP indices. MAP was excluded because of its weak association. Because the decrease in the –2 log likelihood statistic attributable to any 2 BP indices was 10.72_(2BP), the decrease attributable to the addition of a second BP index to a model containing a different initial BP index was the difference between 10.72_(2BP) and the initial decrease attributable to the first BP index. Therefore, the –2 log likelihood was decreased to 7.96 (10.72_(2BP)–2.76_(DBP); P=0.005) by the addition of SBP to a model containing DBP and to a similar order of magnitude, 3.53 (10.72_(2BP)–7.19_(SBP); P=0.06), when DBP was added to a model containing SBP (model 1). In contrast, the decrease in the –2 log likelihood when PP was added to a model containing SBP (3.53 [10.72_(2BP)–7.19_(SBP)]; P=0.06) was 50x larger than when SBP was added to a model containing PP (0.07 [10.72_(2BP)–10.65_(PP)]; P=0.79; model 2, Figure 2A). Similarly, the decrease in the –2 log likelihood was again much larger (112x) when PP was added to a model containing DBP (7.96 [10.72_(2BP)–2.76_(DBP)]; P=0.005) than when DBP was added to a model containing PP (0.07 [10.72_(2BP)–10.65_(PP)]; P=0.79; model 3, Figure 2B).

View larger version (11K): [in this window] [in a new window]   Figure 2. Decrease in the –2 log likelihood when adding SBP to model that contains PP and vice versa (A; model 2) and adding DBP to model that contains PP and vice versa (B; model 3), in a Cox proportional hazards regression model predicting stroke mortality adjusted for age, gender, ethnicity, cigarette smoking, diabetes, cholesterol, and body mass index.

	Discussion

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Our main finding was that PP was more predictive of stroke mortality than SBP, DBP, or MAP in of individuals with ISH. In our study, SBP (positively) and DBP (negatively) were significantly associated with stroke mortality when considered separately.

With increased peripheral resistance, increased cardiac output, or both, which begins sometimes in young individuals and often in aging subjects, SBP and DBP rise progressively with age.³ In contrast, because large-artery stiffness increases in middle-aged and elderly individuals,² SBP rises but DBP falls, resulting in an increased PP, often with preservation of MAP in a stable, normal level.³ An increase in SBP with fixed DBP and a decrease in DBP with fixed SBP occur solely with an increase in PP. These findings imply that in persons with ISH, stroke mortality is more related to increased large-artery stiffness than to increased peripheral vascular resistance. These analyses may be more relevant to ischemic rather than cerebral hemorrhagic stroke. A major limitation of this study was the lack of knowledge about treatment of systolic hypertension during follow-up. Our data suggest that stroke mortality is more related to the pulsatile component, a marker for large-artery stiffness, rather than the steady component, which reflects peripheral resistance, of BP.

	Acknowledgments

 
This study was supported by a grant from the National Heart, Lung and Blood Institute (KO8 HL 03681) and by a grant from the American Heart Association (9750703N). The authors would like to thank the steering committee members of the Women’s Pooling Project for their participation in the project, including Ralph D’Agostino, Boston University; Elizabeth Barrett-Connor, University of California San Diego; Victor Hawthorne, University of Michigan; Millicent Higgins, University of Michigan; William Kannel, Framingham Study; Julian Keil, Medical University of South Carolina; Michael Stern, University of Texas, University of Maryland School of Medicine; Susan Sutherland, Research Institute at Mission St. Joseph’s; H. Al Tyroler, University of North Carolina; and Aaron Folson, University of Minnesota.

Received January 11, 2005; revision received February 24, 2005; accepted March 1, 2005.

	References

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1. Kannel WB, Wolf PA, McGee DL, Dawber TR, McNamara P, Castelli WP. Systolic blood pressure, arterial rigidity, and risk of stroke. The Framingham Study. J Am Med Assoc. 1981; 245: 1225–1229.[Abstract]
2. Kelly R, Hayward C, Avolio A, O’Rourke M. Noninvasive determination of age-related changes in the human arterial pulse. Circulation. 1989; 80: 1652–1659.[Abstract/Free Full Text]
3. Berne RM, Levy MN. Cardiovascular Physiology. St. Louis, Mo: CV Mosby; 2001.
4. Vogt TM, Ireland CC, Black D, Camel G, Hughes G. Recruitment of elderly volunteers for a multicenter clinical trial: the SHEP pilot study. Control Clin Trials. 1986; 7: 118–133.[CrossRef][Medline] [Order article via Infotrieve]
5. Horenstein RB, Smith DE, Mosca L. Cholesterol predicts stroke mortality in the Women’s Pooling Project. Stroke. 2002; 33: 1863–1868.[Abstract/Free Full Text]
6. Collett D. Modeling Survival Data in Medical Research. London, UK: Chapman & Hall; 1994.

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This Article Abstract Full Text (PDF) All Versions of this Article: 36/6/1288    most recent 01.STR.0000166201.79222.4dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Paultre, F. Articles by Mosca, L. Search for Related Content PubMed PubMed Citation Articles by Paultre, F. Articles by Mosca, L. Pubmed/NCBI databases Medline Plus Health Information High Blood Pressure Stroke Related Collections Peripheral vascular disease