Donate Help Contact The AHA Sign In Home
American Heart Association
Stroke
Search: search_blue_button Advanced Search
Correction for Lawes et al., Stroke 35 (3) 776-785.
« Previous Article | Table of Contents | Next Article »
Stroke. 2004;35:1024-1033

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lawes, C. M.M.
Right arrow Articles by Rodgers, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lawes, C. M.M.
Right arrow Articles by Rodgers, A.
Right arrowPubmed/NCBI databases
Medline Plus Health Information
*Stroke

(Stroke. 2004;35:1024.)
© 2004 American Heart Association, Inc.

Blood Pressure and Stroke

An Overview of Published Reviews

Carlene M.M. Lawes, MBChB, FAFPHM, PhD; Derrick A. Bennett, MSc, PhD, CStat; Valery L. Feigin, MD, MSc, PhD Anthony Rodgers, MBChB, FAFPHM, PhD

From the Clinical Trials Research Unit, Department of Medicine, University of Auckland, Auckland, New Zealand.

Correspondence to Carlene Lawes, Clinical Trials Research Unit, Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand. E-mail c.lawes{at}ctru.auckland.ac.nz

Abstract

Background— The last few years have seen a considerable increase in the amount of information available concerning blood pressure (BP) and stroke associations. This article provides an overview of published reviews of the effects on stroke seen in trials of BP-lowering drugs and compares these with the results available from cohort studies.

Summary of Review— We present a review of major overviews of prospective cohort studies and an updated meta-analysis of >40 randomized controlled trials of BP lowering, which included >188 000 participants and approximately 6800 stroke events. Cohort studies now indicate that in the Asia Pacific region as well as in North America and Western Europe, each 10 mm Hg lower systolic BP is associated with a decrease in risk of stroke of approximately one third in subjects aged 60 to 79 years. The association is continuous down to levels of at least 115/75 mm Hg and is consistent across sexes, regions, and stroke subtypes and for fatal and nonfatal events. The proportional association is age dependent but is still strong and positive in those aged 80 years. Data from randomized controlled trials, in which mean age at event was approximately 70 years, indicate that a 10 mm Hg reduction in systolic BP is associated with a reduction in risk of stroke of approximately one third. Per mm Hg systolic BP reduction, the relative benefits for stroke appear similar between agents, by baseline BP levels, and whether or not individuals have a past history of cardiovascular disease. There is, however, evidence of greater benefit with a larger BP reduction.

Conclusions— The epidemiologically expected benefits of BP lowering for stroke risk reduction are broadly consistent across a range of different population subgroups. There are greater benefits from larger BP reductions, and initiating and maintaining BP reduction for stroke prevention is a more important issue than choice of initial agent.


Key Words: blood pressure • cohort studies • epidemiology • meta-analysis • randomized controlled trials • stroke

The risk of stroke increases continuously above blood pressure (BP) levels of approximately 115/75 mm Hg. Since the association is steep, and BP levels are high in most adult populations, almost two thirds of stroke burden globally is attributable to nonoptimal BP (ie, >115/75 mm Hg).1 Approximately two thirds of this burden occurs in middle-aged subjects (45 to 69 years), and approximately two thirds occurs in developing regions.

In 1990 it was demonstrated that in North American and Western European populations, a 5 mm Hg lower diastolic blood pressure (DBP) was associated with a 30% to 40% lower stroke risk,2 and this was reversed within a few years of BP lowering.3 Since then, further evidence has become available, especially in the elderly and in the Asia-Pacific region and from many more trials comparing different agents, more intensive and less intensive BP-lowering regimens, and BP lowering in those without hypertension. This article reviews published trial meta-analyses of the impact of pharmacological BP-lowering therapies on stroke across all population groups. The results are compared with overviews of cohort study data that assessed the association between BP and stroke in a range of populations. The main gaps in current research and the clinical and public health implications of the association of BP with stroke are also discussed.

Methods

Prospective Cohort Studies
Published overviews of cohort studies were identified by a search of MEDLINE and EMBASE databases with key words overview, meta-analysis, blood pressure, stroke or cerebrovascular or cardiovascular disease, cohort study or prospective study, and comparative study. Overviews were included if they were published or data were accessible by May 1, 2003, and if they provided data on inclusion criteria, number and regions of the cohort studies included, number of participants and demographics, duration of follow-up, disease end points, and methods of analyses. Results were independently extracted and summarized by 2 reviewers, but no additional analyses were conducted.

Randomized Controlled Trials
Meta-analyses of trials of BP-lowering agents were identified by a MEDLINE and EMBASE search with search terms overview, meta-analysis, blood pressure or hypertension, stroke or cerebrovascular or cardiovascular disease, and randomized controlled trial. Data from individual trials included in these meta-analyses were included if they were published before May 1, 2003, and if they provided data on inclusion criteria, total number of participants and demographics, randomization method, trial interventions, trial end points, duration of follow-up, and net reduction in BP (ie, treatment effect). Data from individual studies, from both the trial and meta-analytic publications, were independently extracted by 2 reviewers. In some cases, existing meta-analyses of trials3–11 included the most recent data on individual trials, and therefore these were included in the final meta-analyses.

Core baseline and outcome data were extracted, and trials included in the meta-analysis were stratified into the following 3 subgroups to reduce clinical heterogeneity: (1) drug versus placebo or no treatment, (2) more intensive dose of drug versus less intensive dose of drug, and (3) drug versus drug. The net difference in BP between, for example, the treatment and placebo groups was calculated; this reflects the true difference in BP achieved as the influence of regression to the mean (which would be evident in both groups) is removed. The updated meta-analysis was based on summary data rather than individual participant data. The relative risk was computed as the measure of effect size for each trial and subgroup of trials. Statistical heterogeneity was assessed with the use of the standard Q statistic for heterogeneity, with a probability value of <0.1 used to indicate evidence of heterogeneity. A less stringent probability value of 0.1 was used because it is well known that tests of heterogeneity have low statistical power. If there was no evidence of statistical heterogeneity when this criterion was used, then the results were combined with the use of the standard inverse-variance weighted fixed effect approach.12 If there was evidence of statistical heterogeneity between the trials, attempts were made to explore potential sources of heterogeneity. If this was not possible, the random effects approach of DerSimonian and Laird13 was used as part of a sensitivity analysis to assess the robustness of the conclusions. When there were sufficient studies, evidence of publication bias was checked with the use of standard funnel plots.14

For each subgroup of trials, the weighted mean age, weighted mean follow-up, and weighted mean BP reduction were estimated. Trials were weighted by sample size and, in a sensitivity analysis, by number of stroke events.

Results

Prospective Cohort Studies
Five overviews of cohort studies assessing the association between BP and cardiovascular disease were identified. The MacMahon2 and Prospective Studies Collaboration (PSC)15,16 overviews included cohorts predominantly from the United Kingdom, United States, and Europe. Cohorts in the MacMahon2 and first PSC15 review were subsequently included in the later PSC review.16 The Eastern Stroke and Coronary Heart Disease Collaborative Research17 overview is a subset of the Asia Pacific Cohort Studies Collaboration (APCSC),18 which comprises cohorts from Mainland China, Hong Kong, Taiwan, Japan, Singapore, South Korea, Australia, and New Zealand. The PSC and APCSC overviews included almost 1 million and >420 000 individuals, respectively; both analyzed individual participant data and corrected for regression dilution bias to reflect true or "usual" BP levels.16,18 In total, 7 cohorts were included in both the PSC and APCSC overviews, representing <5% and <10% of participants, respectively. The main characteristics and results of the overviews are summarized in Table 1.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Major Overviews of Prospective Cohort Studies

An important finding in all overviews was that the association between BP and risk of stroke was continuous and log linear. Therefore, a given absolute difference in usual BP was associated with a similar relative risk reduction of stroke at all levels of BP. There was no evidence of a threshold below which levels of BP were no longer associated with lower relative risk of stroke, down to approximately 115 mm Hg systolic blood pressure (SBP) or 75 mm Hg DBP.16,18 All overviews commented on the statistical heterogeneity between studies, and age appeared to be an important factor,16,18 explaining approximately 80% of the between-study heterogeneity in APCSC.18 The strength of the overall association was not altered by restricting analyses to those with and without a history of coronary heart disease at baseline or by controlling for additional cardiovascular risk factors.16,18

The overall risk estimates provided by APCSC,18 PSC,16 and previous meta-analyses2,15,17 (a 5 mm Hg lower DBP or 10 mm Hg lower SBP was associated with approximately a 30% to 40% lower risk of stroke) were influenced by the mean age of the cohorts, as the association of BP with stroke varied with age. The proportional change in stroke risk per unit change in BP was less extreme in old age than in middle age (Figure 1), but the relationship remained strong and positive for all age groups.16,18 Age attenuation limits the ability to directly compare the summary relative risk estimates across the overviews, but the 2 recent overviews that have published age-specific relative risks had similar results (Table 1)16,18; a 10 mm Hg lower SBP was associated with approximately a 40% to 50%, 30% to 40%, and 20% to 30% lower risk of stroke in those aged <60 years, 60 to 69 years, and >=70 years, respectively. There has been no evidence in any of the overviews that the strength of association between BP and stroke varied by sex2,15,16,18 or for fatal and nonfatal stroke events.2,18 Regional comparisons in APCSC and PSC suggested that the association between BP and stroke in Asia was similar or even slightly steeper than in Australia and New Zealand,18 Europe,16 and the Unites States16 after standardization for age. In these 2 overviews the associations of BP with stroke subtypes were broadly similar,16,18 although low rates of CT/MRI confirmation would tend to obscure any differences.



View larger version (25K):
[in this window]
[in a new window]
  		Figure 1. Usual SBP and risk of stroke by age, with data from prospective cohort study overviews. Data are shown from the APCSC18 and PSC16 demonstrating the associations between usual SBP and risk of stroke plotted by age groups defined by age at risk on a log scale. The x-axis coordinate for each group is the mean follow-up SBP. The y-axis coordinate is the hazard ratio computed by the floating absolute risk technique,93 which enabled the comparison between pairs of exposure groups rather than comparisons between each exposure group and a reference group. The solid squares are larger where there are more events because their size is proportional to the inverse variance; vertical lines represent 95% CI. (Figures reprinted with permission from Elsevier [Lancet] and Lippincott Williams & Wilkins [J Hypertens.])

Randomized Controlled Trials
Randomized controlled trials provide data on the impact of BP lowering on short-term stroke outcomes, which is relevant in assessing the extent to which the epidemiologically expected reductions in stroke are produced.2,3

Randomized Controlled Trials Comparing Antihypertensive Drugs With a Placebo (or No Treatment)
Seventeen trials compared the effects of ß-blocker and/or diuretic with a placebo or no treatment; in 6 trials the comparison drug was angiotensin-converting enzyme (ACE) inhibitors, and in 2 it was calcium antagonists (Table 2).27,47,50–79 In total, there were >73 500 participants and almost 2900 stroke events recorded in these trials. Weighted mean follow-up time for the 3 groups of trials ranged from 2.8 to 4.6 years, and the weighted mean age of participants ranged from 57 to 68 years. There was clear evidence of a reduction in stroke risk with BP lowering with each drug versus placebo comparison (P<0.005), with pooled relative risk reductions for ß-blocker and/or diuretic, ACE inhibitors, and calcium antagonists of 35%, 28%, and 39%, respectively. These broadly similar relative risk reductions were achieved with weighted mean reductions in BP (SBP/DBP) of 13/6, 5/2, and 10/5 mm Hg, respectively. While the BP reductions appeared less for the ACE inhibitor versus placebo trials, there is also greater uncertainty over the BP reductions in this subgroup.19 There was no evidence of small study bias20 as assessed by a funnel plot14 (not shown) and no significant statistical heterogeneity in any of the 3 subgroup comparisons.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Randomized Controlled Trials Comparing Antihypertensive Drugs to a Placebo (or No Treatment)

The trials comparing antihypertensive drugs with a placebo (or no treatment) were stratified by several trial characteristics such as mean age at entry, baseline BP, and history of cardiovascular disease (Figure 2). Overall, there was a reduction in risk of stroke of 30% and a risk reduction of approximately 30% to 40% in most subgroups. However, in several groups the risk reduction appeared to be greater with larger net reduction in BP, for example, in those with no past history of stroke/transient ischemic attack or vascular disease.



View larger version (29K):
[in this window]
[in a new window]
  		Figure 2. Randomized controlled trials comparing antihypertensive drugs with a placebo (or no treatment) by subgroup. The meta-analyses of BP-lowering trials are presented stratified into subgroups on the basis of mean age of trial participants at entry, baseline SBP level, and whether trial participants predominantly had a history of stroke/transient ischemic attack (TIA) or vascular disease. The diamonds are centered on the pooled estimate of effect and represent 95% CI. The solid diamond represents the pooled relative risk and 95% CI for all contributing trials.

Randomized Controlled Trials Comparing More Intensive Versus Less Intensive Antihypertensive Drug Regimens
Three individually inconclusive clinical trials including a total of 20 408 participants and 384 stroke events compared treatment regimens of different intensities21–24 (Table 3). The meta-analysis suggested that additional benefit may be gained from a more intensive treatment regimen (relative risk reduction of 20%; P=0.04). There was no significant statistical heterogeneity.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Randomized Controlled Trials Comparing More Intensive vs Less Intensive Antihypertensive Drug Regimens

Randomized Controlled Trials Comparing Different Antihypertensive Drugs
Fifteen trials compared the effects of different types of antihypertensive drugs, with 2 trials including several drug versus drug comparisons (Table 4).22–24,46,80–92 In total, there were >96 000 participants and almost 3600 stroke events recorded over a mean follow-up time of 4 to 5 years. The weighted mean reduction in BP in many of the drug versus drug trials was small, often <1 mm Hg SBP and DBP (Table 4). Overall, these trials indicated that there was little difference between the drug classes, with relative risk reductions of 9% (ß-blockers and/or diuretics versus ACE inhibitors), -8% (ß-blockers and/or diuretics versus calcium antagonists), and 11% (calcium antagonists versus ACE inhibitors). These results were of borderline statistical significance. The latter subgroup was the only one in which there was evidence of statistical heterogeneity (P=0.09), and a random effects model gave a nonsignificant relative risk reduction of 5%.


View this table:
[in this window]
[in a new window]
  		TABLE 4. Randomized Controlled Trials Comparing Different Blood Pressure–Lowering Drugs

Net Reduction in BP and Relative Risk Reduction in Stroke
A meta-regression analysis was used to assess the direct relationship between the net reduction in SBP in the 7 trial meta-analyses. The net reduction in SBP was plotted against the relative risk reduction in stroke for each meta-analysis. This plot suggested that a dose-response relationship may exist (Figure 3). A weighted linear regression line was superimposed in which weights are equal to the inverse of the variance for each trial meta-analysis. The slope of this weighted regression line indicated that a 10 mm Hg greater reduction in SBP would be associated with a reduction in risk of stroke of 31% (R2=0.71). The mean weighted follow-up duration for all these trials was 4.5 years, and the mean weighted age of participants at entry into trials was 63 years (the mean age at event is likely to be approximately a decade later). Age-specific analyses from the 2 cohort study overviews16,18 estimated that a 10 mm Hg lower SBP in participants aged 60 to 69 years at event was associated with a risk reduction in stroke of approximately 35%; for those aged >=70 years the risk reduction was 25% to 29% (Table 5). The results from cohort studies and randomized controlled trials are therefore broadly consistent, suggesting that most of the "epidemiologically expected" benefit of BP lowering is achieved within a few years for stroke.



View larger version (14K):
[in this window]
[in a new window]
  		Figure 3. Net reduction in SBP and relative risk reduction in stroke in randomized controlled trials of BP lowering. In a meta-regression, the direct relationship between the net reduction in SBP was plotted against the relative risk reduction in stroke for each of the 7 trial meta-analyses. The slope of the weighted linear regression line (where weights are equal to the inverse of the variance for each trial meta-analysis) indicated that a 10 mm Hg greater reduction in SBP would be associated with a reduction in risk of stroke of 31% (R2=0.71). From left to right, the diamonds represent the meta-analyses for ß-blockers and/or diuretics vs calcium antagonists, calcium antagonists vs ACE inhibitors, and ß-blockers and/or diuretics vs ACE inhibitors; the circle represents the more intensive vs less intensive antihypertensive drug regimens; and the squares are ACE inhibitors vs placebo, calcium antagonists vs placebo, and ß-blockers and/or diuretics vs placebo or no treatment. The sizes of the diamonds, circle, and squares are larger where there are more events because their size is proportional to the inverse variance of that comparison; vertical lines represent 95% CI.


View this table:
[in this window]
[in a new window]
  		TABLE 5. Relative Risk Reduction in Stroke With a Reduction in Systolic Blood Pressure Predicted From Cohort Studies and Observed From Randomized Controlled Trials

Discussion

Cohort studies have demonstrated that the strong association between BP and stroke appears to be continuous down to levels of at least 115/75 mm Hg. The strength of the associations was similar for men and women and for fatal and nonfatal events but attenuated with age.2,15–18 Despite a potentially weaker relative association for older age groups, the higher overall stroke rate in this group means that in absolute terms, the benefits of a given reduction in BP are likely to be greater. The analyses have not consistently demonstrated a difference in the association between intracerebral hemorrhage and ischemic stroke; however, only approximately one half of stroke subtypes were confirmed (CT, MRI, or autopsy). Regional comparisons are very limited because most of the cohort studies have been conducted primarily in the "developed" parts of the world; however, the broad consistency of the results across overviews was more evident than any differences. This suggests that the proportional associations are likely to be reasonably generalizable to the many populations in the world (eg, Africa, South America) for which there are limited data on stroke epidemiology.25

Data from trials provide more reliable data on the likely short-term benefits of BP lowering on stroke. As with the cohort data, randomized controlled trials have been conducted predominantly in populations of Western countries, and data for developing countries (where approximately three quarters of stroke deaths occur worldwide26) are very scarce. The results of the updated meta-analysis of trials are consistent with those of several previous meta-analyses and confirmed the risk reduction of stroke with BP lowering compared with placebo (regardless of the agent used) as being between 30% and 40%. Previous analyses have also found no evidence of a difference in effect size for men and women or for fatal and nonfatal events.3–8 Limited data were available on treatment effects by age, and the treatment effects by age within individual trials27 and between trials4,5,9,10,28 have not been consistent. However, the trials were often not powered for age subgroup analyses and often included only a narrow age band. Few data are available on stroke subtypes, limiting the scope for meta-analyses. The limited data from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)27 and the Heart Outcomes Prevention Evaluation (HOPE) study29 are insufficient to draw definitive conclusions regarding the impact of BP lowering on stroke subtypes. Analyses have indicated, however, that a more intensive BP-lowering regimen with a given agent may produce a greater risk reduction than a less intensive regimen and that overall the trials demonstrate a dose-response relationship between magnitude of BP reduction and reduction in risk of stroke.

When different classes of BP-lowering drugs were directly compared, there was very little difference in either the magnitude of the BP reduction achieved or the impact of different agents on stroke. The similarities between the effects of different drug classes are more striking than the differences, but there is uncertainty over the extent to which any differences are explained by differences in BP reduction and chance. One arm of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)30 and the Losartan Intervention For Endpoint reduction in hypertension study (LIFE)31,32 were not included in the meta-analysis because no other trials included the same classes of drugs. They indicated that there was a higher risk of stroke in the {alpha}-adrenergic blocker group compared with diuretics30 and that angiotensin II blockers may have greater impact on stroke than ß-blockers.31,32

Shape and Size of Association Between BP and Stroke
There has been considerable debate over the shape of the association between BP and stroke. The data presented here from cohort studies suggested a continuous log-linear association. However, some other cohort data appear to have demonstrated a J-shaped curve,33–37 and it has been suggested that this relationship indicates that BP has been lowered too far and that cerebral blood flow is compromised, leading to ischemia. It is more likely to reflect deteriorating health, which accounts for both falling pressure and a greater likelihood of a cardiovascular disease event, but the 2 factors may not be causally related.38–43 Several trials have found no evidence of a J-curve association despite including subgroups of patients susceptible to reduced perfusion.44–47 The large PROGRESS48 and HOPE29 trials found no evidence of a J-curve association across a wide range of BP levels. Overall, these results support a log-linear association and indicate that a potential J-curve relationship should not detract attention from the major benefits of BP lowering.

A key finding from this article is that the 7 meta-analyses of randomized controlled trials of BP lowering and stroke suggest a dose-response relationship. At mean age at baseline of approximately 63 years, a 10 mm Hg reduction in SBP was associated with a risk reduction in stroke of 31%. Given that most of these individuals would not have experienced their stroke event until approximately a decade later, the results are consistent with the predicted reduction in stroke risk from the cohort study data. This indicates that most of the epidemiologically expected benefit of BP lowering may be achieved within a few years for stroke.

Future Research and Implications for Prevention
Research and analyses from cohort study collaborations such as APCSC and meta-analysis of individual participant trial data improve the understanding of the associations between BP and stroke and the potential benefits of BP lowering in different population subgroups. Additional analyses are able to examine the combined impact of multiple risk factors on stroke risk. BP intervention strategies would be greatly enhanced if these data were also used in the improvement of risk prediction frameworks to better identify those at higher absolute risk of cardiovascular disease. Development of simple versions of these risk prediction tools would be of particular value in developing regions where much of the future cardiovascular disease burden is likely to occur.1,49

Future trial analyses should focus on the presence or absence of age attenuation in the effect of BP lowering. This would require comparison of age-specific, follow-up time–specific, and end point–specific analyses of individual participant data from both observational studies (such as APCSC) and clinical trials (such as the Blood Pressure Lowering Treatment Trialists’ Collaboration11). Given that most individuals require combination therapy, it is also important to shift the focus of trials from comparisons of the short-term benefits of individual drugs. Instead, future trials should aim to determine the optimal combination therapy and the potential long-term benefits of different antihypertensive regimens in different population subgroups. While there may be some differences between BP-lowering agents, the relative differences between these agents are minor compared with the relative benefits of any BP-lowering agent versus no treatment.

Finally, it is important to acknowledge that treatment of high-risk groups will only partially address the growing cardiovascular disease epidemic. Data presented in this article indicated that the relative benefits of BP lowering are not only limited to those classified as hypertensive but would also be evident in those with normal or below normal BP. These relative benefits appear broadly consistent across many population subgroups. Other important areas of research therefore include exploration of cost-effective strategies to bring about population changes in cardiovascular risk factors such as BP. Such initiatives would complement targeted treatment approaches and would not only benefit the developed world but could potentially arrest the projected increase in cardiovascular disease in developing countries.

Acknowledgments

This study was supported by a Health Research Council (New Zealand) fellowship to Dr Lawes. Dr Rodgers is a National Health Foundation (New Zealand) Senior Research Fellow. We thank Varsha Parag and Ruey-Bin Lin for statistical assistance and Clarissa Could-Thorpe for secretarial support.

Footnotes

The article entitled "Blood Pressure and Stroke: An Overview of Published Reviews," by Lawes et al1 contained incorrect data resulting from a production error. The corrected article appears below. The publisher regrets the error.

1[Correction for Vol 35, Number 3, March 2004. Pages 776–785.] Back

Received August 14, 2003; revision received October 7, 2003; accepted November 19, 2003.

References

  1. World Health Organisation. The World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva, Switzerland: World Health Organisation; 2002.
  2. MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J. Blood pressure, stroke, and coronary heart disease, part I: prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990; 335: 765–774.[CrossRef][Medline] [Order article via Infotrieve]
  3. Collins R, Peto R, MacMahon S, Hebert P, Fiebach NH, Eberlein KA, Godwin J, Qizilbash N, Taylor JO, Hennekens CH. Blood pressure, stroke, and coronary heart disease, part 2: short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet. 1990; 335: 827–838.[CrossRef][Medline] [Order article via Infotrieve]
  4. MacMahon S, Rodgers A. The effects of anti-hypertensive treatment on vascular disease: reappraisal of the evidence in 1994. J Vasc Med Biol. 1993; 4: 265–271.
  5. MacMahon S, Rodgers A. The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives. Clin Exp Hypertens. 1993; 15: 967–978.[Medline] [Order article via Infotrieve]
  6. Insua JT, Sacks HS, Lau TS, Lau J, Reitman D, Pagano D, Chalmers TC. Drug treatment of hypertension in the elderly: a meta-analysis. Ann Intern Med. 1994; 121: 355–362.[Abstract/Free Full Text]
  7. Gueyffier F, Boutitie F, Boissel JP, Pocock S, Coope J, Cutler J, Ekbom T, Fagard R, Friedman L, Kerlikowske K, Perry M, Prineas R, Schron E, for the INDANA Investigators. Effect of antihypertensive drug treatment on cardiovascular outcomes in women and men: a meta-analysis of individual patient data from randomized, controlled trials. Ann Intern Med. 1997; 126: 761–767.[Abstract/Free Full Text]
  8. He J, Whelton PK. Elevated systolic blood pressure as a risk factor for cardiovascular and renal disease. J Hypertens Suppl. 1999; 17: S7–S13.[Medline] [Order article via Infotrieve]
  9. Gueyffier F, Boutitie F, Boissel JP, Coope J, Cutler J, Ekbom T, Fagard R, Friedman L, Perry HM, Pocock S. INDANA: a meta-analysis on individual patient data in hypertension: protocol and preliminary results. Therapie. 1995; 50: 353–362.[Medline] [Order article via Infotrieve]
  10. Gueyffier F, Froment A, Gouton M. New meta-analysis of treatment trials of hypertension: improving the estimate of therapeutic benefit. J Hum Hypertens. 1996; 10: 1–8.[Medline] [Order article via Infotrieve]
  11. Neal B, MacMahon S, Chapman N, for the Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Lancet. 2000; 356: 1955–1964.[CrossRef][Medline] [Order article via Infotrieve]
  12. Hedges LV, Olkin I. Statistical Methods for Meta-analysis. London, UK: Academic Press; 1985.
  13. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986; 7: 177–188.[CrossRef][Medline] [Order article via Infotrieve]
  14. Light RJ, Pillemer DB. Summing Up: The Science of Reviewing Research. Cambridge, Mass: Harvard University Press; 1984.
  15. Prospective Studies Collaboration. Cholesterol, diastolic blood pressure, and stroke: 13,000 strokes in 45,000 people in 45 prospective cohorts. Lancet. 1995; 346: 1647–1653.[CrossRef][Medline] [Order article via Infotrieve]
  16. Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002; 360: 1903–1913.[CrossRef][Medline] [Order article via Infotrieve]
  17. Eastern Stroke and Coronary Heart Disease Collaborative Research Group. Blood pressure, cholesterol, and stroke in eastern Asia. Lancet. 1998; 352: 1801–1807.[CrossRef][Medline] [Order article via Infotrieve]
  18. Asia Pacific Cohort Studies Collaboration. Blood pressure and cardiovascular disease in the Asia Pacific region. J Hypertens. 2003; 21: 707–716.[CrossRef][Medline] [Order article via Infotrieve]
  19. Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE substudy. Hypertension. 2001; 38: E28–E32.[CrossRef][Medline] [Order article via Infotrieve]
  20. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: investigating and dealing with publication and other biases in meta-analysis. BMJ. 2001; 323: 101–105.[Free Full Text]
  21. Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S, for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998; 351: 1755–1762.[CrossRef][Medline] [Order article via Infotrieve]
  22. Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. 1998; 338: 645–652.[Abstract/Free Full Text]
  23. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317: 703–713.[Abstract/Free Full Text]
  24. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998; 317: 713–720.[Abstract/Free Full Text]
  25. Feigin VL, Lawes CMM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003; 2: 43–53.[CrossRef][Medline] [Order article via Infotrieve]
  26. Truelsen T, Bonita R, Jamrozik K. Surveillance of stroke: a global perspective. Int J Epidemiol. 2001; 30 (suppl 1): S11–S16.[Free Full Text]
  27. PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001; 358: 1033–1041.[CrossRef][Medline] [Order article via Infotrieve]
  28. Gueyffier F, Bulpitt C, Boissel J-P, Schron E, Ekbom T, Fagard R, Casiglia E, Kerlikowske K, Coope J, for the INDANA Group. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. Lancet. 1999; 353: 793–796.[CrossRef][Medline] [Order article via Infotrieve]
  29. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B, Davies R, Ostergren J. Use of ramipril in preventing stroke: double blind randomised trial. BMJ. 2002; 324: 699–702.[Abstract/Free Full Text]
  30. ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2000; 283: 1967–1975.[Abstract/Free Full Text]
  31. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H, LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359: 995–1003.[CrossRef][Medline] [Order article via Infotrieve]
  32. Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristiansson K, Lederballe-Pederson O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snappin S, LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359: 1004–1010.[CrossRef][Medline] [Order article via Infotrieve]
  33. Stewart IM. Relation of reduction in pressure to first myocardial infarction in patients receiving treatment for severe hypertension. Lancet. 1979; 1: 861–865.[Medline] [Order article via Infotrieve]
  34. Kannel WB, D’Agostino RB, Silbershatz H. Blood pressure and cardiovascular morbidity and mortality rates in the elderly. Am Heart J. 1997; 134: 758–763.[CrossRef][Medline] [Order article via Infotrieve]
  35. Cruickshank JM. J curve in antihypertensive therapy: does it exist? A personal point of view. Cardiovasc Drugs Ther. 1994; 8: 757–760.[CrossRef][Medline] [Order article via Infotrieve]
  36. D’Agostino RB, Belanger AJ, Kannel WB, Cruickshank JM. Relation of low diastolic blood pressure to coronary heart disease death in presence of myocardial infarction: the Framingham Study. BMJ. 1991; 303: 385–389.[Medline] [Order article via Infotrieve]
  37. Farnett L, Mulrow CD, Linn WD, Lucey CR, Tuley MR. The J -curve phenomenon and the treatment of hypertension: is there a point beyond which pressure reduction is dangerous? JAMA. 1991; 265: 489–495.[Abstract]
  38. Alderman MH. Blood pressure J-curve: is it cause or effect? Curr Opin Nephrol Hypertens. 1996; 5: 209–213.[CrossRef][Medline] [Order article via Infotrieve]
  39. MacMahon S, Rodgers A, Neal B, Chalmers J. Blood pressure lowering for the secondary prevention of myocardial infarction and stroke. Hypertension. 1997; 29: 537–538.[Free Full Text]
  40. Sleight P. Lowering of blood pressure and artery stiffness. Lancet. 1997; 349: 362.[CrossRef]
  41. Sleight P. Lowering of blood pressure and artery stiffness. Lancet. 1997; 349: 955–956.[Medline] [Order article via Infotrieve]
  42. Neaton JD, Wentworth D, for the Multiple Risk Factor Intervention Trial Research Group. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease: overall findings and differences by age for 316,099 white men. Arch Intern Med. 1992; 152: 56–64.[Abstract]
  43. Flack JM, Neaton J, Grimm R Jr, Shih J, Cutler J, Ensrud K, MacMahon S, for the Multiple Risk Factor Intervention Trial Research Group. Blood pressure and mortality among men with prior myocardial infarction. Circulation. 1995; 92: 2437–2445.[Abstract/Free Full Text]
  44. McMurray J, McInnes GT. The J-curve hypothesis. Lancet. 1992; 339: 561–562.[Medline] [Order article via Infotrieve]
  45. Pfeffer MA. Angiotensin-converting enzyme inhibition in congestive heart failure: benefit and perspective. Am Heart J. 1993; 126 (pt 2): 789–793.[CrossRef][Medline] [Order article via Infotrieve]
  46. Hansson L, Lindholm LH, Ekbom T, Dahlof B, Lanke J, Schersten B, Wester PO, Hedner T, de Faire U. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity: the Swedish Trial in Old Patients with Hypertension-2 study. Lancet. 1999; 354: 1751–1756.[CrossRef][Medline] [Order article via Infotrieve]
  47. Staessen J, Fagard R, Thijs L, Celis H, Arabidze G, Birkenhager W, Bulpitt C, de Leeuw PD, Dollery C, Fletcher AE, Forette F, Leonetti G, Nachev C, O’Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet. 1997; 350: 757–764.[CrossRef][Medline] [Order article via Infotrieve]
  48. PROGRESS Collaborative Group. The lowering of blood-pressure after stroke. Lancet. 2001; 358: 1994–1995.[Medline] [Order article via Infotrieve]
  49. Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability From Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Cambridge, Mass: Harvard University Press; 1996.
  50. Report by the Management Committee. The Australian therapeutic trial in mild hypertension. Lancet. 1980; 1: 1261–1267.[Medline] [Order article via Infotrieve]
  51. Control of moderately raised blood pressure: report of a co-operative randomized controlled trial. BMJ. 1973; 3: 434–436.[Medline] [Order article via Infotrieve]
  52. Carter AB. Hypotensive therapy in stroke survivors. Lancet. 1970; 1: 485–489.[Medline] [Order article via Infotrieve]
  53. Coope J, Warrender TS. Randomised trial of treatment of hypertension in elderly patients in primary care. BMJ. 1986; 293: 1145–1151.[Medline] [Order article via Infotrieve]
  54. The Dutch TIA Trial Study Group. Trial of secondary prevention with atenolol after transient ischemic attack or nondisabling ischemic stroke. Stroke. 1993; 24: 543–548.[Abstract/Free Full Text]
  55. Amery A, Birkenhager W, Brixko P, Bulpitt C, Clement D, Deruyttere M, De Schaepdryver A, Dollery C, Fagard R, Forette F. Mortality and morbidity results from the European Working Party on High Blood Pressure in the Elderly trial. Lancet. 1985; 1: 1349–1354.[Medline] [Order article via Infotrieve]
  56. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program, I: reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA. 1979; 242: 2562–2571.[Abstract]
  57. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program, II: mortality by race-sex and age. JAMA. 1979; 242: 2572–2577.[Abstract]
  58. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-up Program, III: reduction in stroke incidence among persons with high blood pressure. JAMA. 1982; 247: 633–638.[Abstract]
  59. The effect of treatment on mortality in "mild" hypertension: results of the Hypertension Detection and Follow-up Program. N Engl J Med. 1982; 307: 976–980.[Abstract]
  60. Effect of stepped care treatment on the incidence of myocardial infarction and angina pectoris: 5-year findings of the Hypertension Detection and Follow-up Program. Hypertension. 1984; 6(pt 2): I198–I206.
  61. Hypertension-Stroke Cooperative Study Group. Effect of antihypertensive treatment on stroke recurrence. JAMA. 1974; 229: 409–418.[CrossRef][Medline] [Order article via Infotrieve]
  62. MRC Working Party. Medical Research Council trial of treatment of hypertension in older adults: principal results. BMJ. 1992; 304: 405–412.[Medline] [Order article via Infotrieve]
  63. Medical Research Council Working Party. MRC trial of treatment of mild hypertension: principal results. BMJ. 1985; 291: 97–104.[Medline] [Order article via Infotrieve]
  64. Helgeland A. Treatment of mild hypertension: a five year controlled drug trial: the Oslo study. Am J Med. 1980; 69: 725–732.[CrossRef][Medline] [Order article via Infotrieve]
  65. Leren P, Helgeland A. Oslo Hypertension Study. Drugs. 1986; 31 (suppl 1): 41–45.[Medline] [Order article via Infotrieve]
  66. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 265: 3255–3264.[Abstract]
  67. Dahlof B, Lindholm LH, Hansson L, Schersten B, Ekbom T, Wester PO. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Lancet. 1991; 338: 1281–1285.[CrossRef][Medline] [Order article via Infotrieve]
  68. Smith WM. Treatment of mild hypertension: results of a ten-year intervention trial. Circ Res. 1977; 40 (suppl 1): I98–I105.[Medline] [Order article via Infotrieve]
  69. Effects of treatment on morbidity in hypertension: results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967; 202: 1028–1034.[CrossRef][Medline] [Order article via Infotrieve]
  70. Effects of treatment on morbidity in hypertension, II: results in patients with diastolic blood pressure averaging 90 through 114 mm Hg. JAMA. 1970; 213: 1143–1152.[CrossRef][Medline] [Order article via Infotrieve]
  71. Perry HM Jr. Treatment of mild hypertension: preliminary results of a two-year feasibility trial. Circ Res. 1977; 40 (suppl 1): I180–I187.[Medline] [Order article via Infotrieve]
  72. Veterans Administration–National Heart, Lung, and Blood Institute Study Group for Evaluating Treatment in Mild Hypertension. Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial: plan and preliminary results of a two-year feasibility trial for a multicenter intervention study to evaluate the benefits versus the disadvantages of treating mild hypertension. Ann N Y Acad Sci. 1978; 304: 267–292.[Abstract]
  73. Wolff FW, Lindeman RD. Effects of treatment in hypertension: results of a controlled study. J Chron Dis. 1966; 19: 227–240.[CrossRef][Medline] [Order article via Infotrieve]
  74. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G, for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000; 342: 145–153.[Abstract/Free Full Text]
  75. MacMahon S, Sharpe N, Gamble G, Clague A, Mhurchu CN, Clark T, Hart H, Scott J, White H, for the PART-2 Collaborative Research Group. Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease: Prevention of Atherosclerosis with Ramipril. J Am Coll Cardiol. 2000; 36: 438–443.[Abstract/Free Full Text]
  76. Cashin-Hemphill L, Holmvang G, Chan RC, Pitt B, Dinsmore RE, Lees RS, for the QUIET Investigators. Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no answer yet: QUinapril Ischemic Event Trial. Am J Cardiol. 1999; 83: 43–47.[CrossRef][Medline] [Order article via Infotrieve]
  77. Teo KK, Burton JR, Buller CE, Plante S, Catellier D, Tymchak W, et al. Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: the Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). Circulation. 2000; 102: 1748–1754.[Abstract/Free Full Text]
  78. Eriksson S, Olofsson BO, Wester PO. Atenolol in secondary prevention after stroke. Cerebrovasc Dis. 1995; 5: 21–25.
  79. Pitt B, Byington RP, Furberg CD, Hunninghake DB, Mancini GB, Miller ME, Riley W. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. Circulation. 2000; 102: 1503–1510.[Abstract/Free Full Text]
  80. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 288: 2981–2997.[Abstract/Free Full Text]
  81. Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, Johnston CI, McNeil JJ, Macdonald GJ, Marley JE, Morgan TO, West MJ; Second Australian National Blood Pressure Study. A comparison of outcomes with angiotensin-converting–enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003; 348: 583–592.[Abstract/Free Full Text]
  82. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg BE, Wester PO, Bjork JE. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet. 1999; 353: 611–616.[CrossRef][Medline] [Order article via Infotrieve]
  83. Casiglia E, Spolaore P, Mazza A, Ginocchio G, Colangeli G, Onesto C, Di Menza G, Pegoraro L, Ambrosio GB. Effect of two different therapeutic approaches on total and cardiovascular mortality in a Cardiovascular Study in the Elderly (CASTEL). Jpn Heart J. 1994; 35: 589–600.[Medline] [Order article via Infotrieve]
  84. Black HR, Elliott WJ, Grandits G, Grambsch P, Lucente T, White WB, Neaton JD, Grimm RH Jr, Hansson L, Lacourciere Y, Muller J, Sleight P, Weber MA, Williams G, Wittes J, Zanchetti A, Anders RJ, CONVINCE Research Group. Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial. JAMA. 2003; 289: 2073–2082.[Abstract/Free Full Text]
  85. Zanchetti A, Bond MG, Hennig M, Neiss A, Mancia G, Dal Palu C, Hansson L, Magnani B, Rahn KH, Reid JL, Rodicio J, Safar M, Eckes L, Rizzini P, European Lacidipine Study on Atherosclerosis Investigators. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation. 2002; 106: 2422–2427.[Abstract/Free Full Text]
  86. Brown MJ, Palmer CR, Castaigne A, de Leeuw PW, Mancia G, Rosenthal T, Ruilope LM. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the international nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet. 2000; 356: 366–372.[CrossRef][Medline] [Order article via Infotrieve]
  87. Borhani NO, Mercuri M, Borhani PA, Buckalew VM, Canossa-Terris M, Carr AA, Kappagoda T, Rocco MV, Schnaper HW, Sowers JR, Bond MG. Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS): a randomized controlled trial. JAMA. 1996; 276: 785–791.[Abstract]
  88. National Intervention Cooperative Study in Elderly Hypertensives Study Group. Randomized double-blind comparison of a calcium antagonist and a diuretic in elderly hypertensives. Hypertension. 1999; 34: 1129–1133.[Abstract/Free Full Text]
  89. Hansson L, Hedner T, Lund-Johansen P, Kjeldsen SE, Lindholm LH, Syvertsen JO, Lanke J, de Faire U, Dahlof B, Karlberg BE. Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study. Lancet. 2000; 356: 359–365.[CrossRef][Medline] [Order article via Infotrieve]
  90. Zanchetti A, Rosei EA, Dal Palu C, Leonetti G, Magnani B, Pessina A. The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness. J Hypertens. 1998; 16: 1667–1676.[CrossRef][Medline] [Order article via Infotrieve]
  91. Rosei EA, Dal Palu C, Leonetti G, Magnani B, Pessina A, Zanchetti A, for the VHAS Investigators. Clinical results of the Verapamil in Hypertension and Atherosclerosis Study. J Hypertens. 1997; 15: 1337–1344.[CrossRef][Medline] [Order article via Infotrieve]
  92. Tatti P, Pahor M, Byington RP, Di Mauro P, Guarisco R, Strollo G, Strollo F. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998; 21: 597–603.[Abstract]
  93. Easton DF, Peto J, Babiker AG. Floating absolute risk: an alternative to relative risk in survival and case-control analysis avoiding an arbitrary reference group. Stat Med. 1991; 10: 1025–1035.[Medline] [Order article via Infotrieve]



This article has been cited by other articles:


Home page
 PNHome page
C Sudlow
Preventing further vascular events after a stroke or transient ischaemic attack: an update on medical management
Practical Neurology, June 1, 2008; 8(3): 141 - 157.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
N. S. Beckett, R. Peters, A. E. Fletcher, J. A. Staessen, L. Liu, D. Dumitrascu, V. Stoyanovsky, R. L. Antikainen, Y. Nikitin, C. Anderson, et al.
Treatment of Hypertension in Patients 80 Years of Age or Older
N. Engl. J. Med., May 1, 2008; 358(18): 1887 - 1898.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
A. Towfighi, J. L. Saver, R. Engelhardt, and B. Ovbiagele
A midlife stroke surge among women in the United States
Neurology, November 13, 2007; 69(20): 1898 - 1904.
[Abstract] [Full Text] [PDF]

Home page
 CJASNHome page
S. Khella and M. B. Bleicher
Stroke and Its Prevention in Chronic Kidney Disease
Clin. J. Am. Soc. Nephrol., November 1, 2007; 2(6): 1343 - 1351.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. M. Samuelson, J. Yamamoto, E. I. Levy, A. H. Siddiqui, and L. N. Hopkins
The Argument to Support Broader Application of Extracranial Carotid Artery Stent Technology
Circulation, October 2, 2007; 116(14): 1602 - 1610.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
L. M. Thorn, C. Forsblom, J. Fagerudd, K. Pettersson-Fernholm, R. Kilpikari, P.-H. Groop, and on behalf of the FinnDiane Study Group
Clustering of Risk Factors in Parents of Patients With Type 1 Diabetes and Nephropathy
Diabetes Care, May 1, 2007; 30(5): 1162 - 1167.
[Abstract] [Full Text] [PDF]

</