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C-Reactive Protein and the Risk of Developing Hypertension
Howard D. Sesso, ScD, MPH;
Julie E. Buring, ScD;
Nader Rifai, PhD;
Gavin J. Blake, MD, MPH;
J. Michael Gaziano, MD, MPH;
Paul M. Ridker, MD, MPH
JAMA. 2003;290:2945-2951.
ABSTRACT
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Context Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce.
Objective To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension.
Design, Setting, and Participants A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected.
Main Outcome Measure Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg.
Results During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP.
Conclusion C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.
INTRODUCTION
The C-reactive protein is a marker of systemic inflammation that has been associated with an increased risk of incident myocardial infarction and stroke.1-5 Inflammation has also been hypothesized to play a role in the development of hypertension, and cross-sectional evidence demonstrates higher C-reactive protein levels among those individuals with elevated blood pressure (BP).6-11 Higher levels of C-reactive protein may increase BP by reducing nitric oxide production in endothelial cells,12-13 resulting in vasoconstriction and increased production of endothelin 1.14-15 C-reactive protein may also function as a proatherosclerotic factor by up-regulating angiotensin type 1 receptor expression.16
Inflammation has been shown to correlate with endothelial dysfunction17 and relate to the renin-angiotensin system.18 As a result, it has been hypothesized that hypertension may be in part an inflammatory disorder. However, clinical data linking inflammation with incident hypertension are scarce.19 We therefore determined whether elevated C-reactive protein levels in normotensive individuals are associated with an increased risk of developing hypertension.
METHODS
Study Population
The Women's Health Study is an ongoing randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer, which began in 1992.20 In 1992, a total of 39 876 female US health professionals aged 45 years or older without prior myocardial infarction, stroke, transient ischemic attack, and cancer (except nonmelanoma skin cancer) were enrolled and randomized into the study.
Before randomization, baseline blood samples were collected from 28 345 participants and stored in liquid nitrogen until analysis. Samples were then transferred to a core laboratory facility in which they were assayed for C-reactive protein with a validated high-sensitivity assay (Denka Seiken Co, Tokyo, Japan).5 Of the samples received, 27 939 were evaluated and assayed for C-reactive protein. The baseline population was then restricted to 20 525 women without hypertension, defined as having no self-reported past or current history of hypertension, no past or current history of antihypertensive treatment, a systolic BP of less than 140 mm Hg, and a diastolic BP of less than 90 mm Hg at study entry. Baseline BP was reported in 1 of 9 ordinal systolic BP categories ranging from less than 110 mm Hg to at least 180 mm Hg and 7 ordinal diastolic BP categories ranging from less than 65 mm Hg to at least 105 mm Hg. A single measurement of self-reported BP in health professionals has been shown to be highly correlated with measured systolic BP (r = 0.72) and diastolic BP (r = 0.60).21
Outcome Ascertainment
Incident cases of hypertension were defined by meeting at least 1 of 4 criteria: self-reports of a new physician diagnosis on follow-up questionnaires at years 1 and 3, and all annual questionnaires thereafter; self-reports of newly initiated antihypertensive treatment at years 1, 3, and 4; self-reported systolic BP of at least 140 mm Hg; or self-reported diastolic BP of at least 90 mm Hg. Women reporting a new physician diagnosis of hypertension also provided the month and year of diagnosis. A missing date for a physician diagnosis or hypertension defined by another criterion was assigned a date of incident hypertension by randomly selecting a date between the current and previous annual questionnaire. Those individuals developing major concomitant diseases, the management of which may have impact on BP, at or after baseline but before the development of hypertension, including myocardial infarction, stroke, pulmonary embolism, and peripheral vascular disease, were censored at that date of diagnosis and not considered an incident case of hypertension. Based on this definition, 5365 cases of incident hypertension developed during a median follow-up of 7.8 years (range, 0.001-8.82 years).
Data Analyses
Women were first compared according to level of C-reactive protein by using mean values or proportions of baseline risk factors to assess potential confounding. Because hormone therapy increases the level of C-reactive protein,22-23 levels were based on the quintiles of C-reactive protein among the subset of women not taking hormone therapy. We used Cox proportional hazards regression model analyses to compute the relative risks (RRs) and 95% confidence intervals (CIs) of incident hypertension for increasing plasma C-reactive protein levels, with the lowest level as the referent. Models first included only C-reactive protein, then were adjusted for age and randomized treatment assignment. The final multivariable model added body mass index (calculated as weight in kilograms divided by the square of height in meters), smoking status, exercise, alcohol consumption, parental history of myocardial infarction before age 60 years, diabetes, postmenopausal hormone use, and hypercholesterolemia (either any baseline history of cholesterol-lowering medication use or a physician diagnosis of high cholesterol or a self-reported cholesterol of at least 240 mg/dL [ 6.22 mmol/L]). Linear trend tests across levels of plasma C-reactive protein levels were performed by using the median value for each level as an ordinal variable.
Both stratified and joint models incorporating C-reactive protein and either systolic BP or diastolic BP were also considered. Women in the upper half of the prehypertension BP classification according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)24 (either systolic BP of 130-139 mm Hg or diastolic BP of 85-89 mm Hg) were excluded from these analyses out of concern for potential misclassification and the vast majority of these women became hypertensive during follow-up. Joint models of C-reactive protein and BP used clinically relevant cut points for C-reactive protein: less than 1, 1 to less than 3, and 3 or more mg/L.25 A test for interaction between C-reactive protein, BP, and the risk of developing hypertension was assessed with C-reactive protein as a continuous variable and BP as an ordinal variable. All analyses were performed with SAS version 8 (SAS Institute Inc, Cary, NC), using a 2-tailed P = .05 for significance.
RESULTS
Baseline characteristics of the study population according to levels of C-reactive protein are shown in Table 1. As expected, traditional coronary risk factors were more prevalent among those participants with elevated levels of C-reactive protein. During a median follow-up of 7.8 years for the 20 525 women comprising the baseline population, 5365 women developed hypertension either on the basis of newly initiated treatment (n = 2295 [43%]) or having a systolic BP of at least 140 mm Hg or diastolic BP of at least 90 mm Hg (n = 3070 [57%]).
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Table 1. Comparison of Baseline Characteristics Among 20 525 Women According to Level of C-Reactive Protein*
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Overall, there was a positive association between increasing levels of C-reactive protein and risk of developing hypertension (Table 2). In crude models, the RRs of developing hypertension increased from the lowest (referent) to the highest level of C-reactive protein (linear trend P<.001), such that those participants with levels of C-reactive protein in excess of 3.5 mg/L had an RR of 2.50 (95% CI, 2.27-2.75). In risk factor–adjusted models as well as those that additionally adjusted for baseline BP, risks were attenuated but retained a positive association with risk of developing hypertension (linear trend P<.001). For example, in models additionally adjusting for baseline BP, women with increasing levels of C-reactive protein had RRs of hypertension of 1.04 (95% CI, 0.92-1.17), 1.11 (95% CI, 0.99-1.24), 1.19 (95% CI, 1.07-1.33), and 1.34 (95% CI, 1.20-1.50; linear trend P<.001). Analyses stratified by use or nonuse of hormone therapy showed essentially identical results. In log-transformed models that considered C-reactive protein as a continuous variable, similar strong effects were observed that were all statistically significant (for 1-SD increase of C-reactive protein, adjusted RR, 1.14; 95% CI, 1.11-1.17).
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Table 2. Hypertension by Levels of C-Reactive Protein in All Women, According to Nonusers and Users of Hormone Therapy
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We also considered more restrictive definitions of hypertension to address potential misclassification. The multivariable RRs of hypertension restricted to women initiating treatment, having a physician diagnosis, having a systolic BP of at least 160 mm Hg, or having a diastolic BP of at least 95 mm Hg during follow-up (4982 of 5365 women developing hypertension) for increasing levels of C-reactive protein were 1.00, 1.06 (95% CI, 0.94-1.20), 1.18 (95% CI, 1.05-1.33), 1.30 (95% CI, 1.16-1.46), and 1.52 (95% CI, 1.36-1.70; linear trend P<.001). Alternatively, analyses of hypertension restricted to women initiating treatment or having a physician diagnosis during follow-up (2295 of 5365 women developing hypertension) resulted in RRs for increasing levels of C-reactive protein of 1.00, 1.03 (95% CI, 0.87-1.22), 1.02 (95% CI, 0.86-1.20), 1.14 (95% CI, 0.97-1.33), and 1.41 (95% CI, 1.20-1.65; linear trend P<.001).
We next examined the age-adjusted and multivariable-adjusted associations between C-reactive protein and the risk of developing hypertension stratified by either systolic BP or diastolic BP. In Table 3, increasing levels of C-reactive protein were associated with an increased risk of developing hypertension at all levels of baseline BP in fully-adjusted models, even among women with baseline systolic BP of less than 110 mm Hg and baseline diastolic BP of less than 65 mm Hg. Additional adjustment for diastolic BP in models stratified by systolic BP, or for systolic BP in models stratified by diastolic BP, did not change the RRs from our fully-adjusted models. The consideration of log-transformed C-reactive protein as a continuous variable also generated statistically significant results decreased to a systolic BP of 110 mm Hg and a diastolic BP of 65 mm Hg (for 1-SD increase of C-reactive protein among women with systolic BP 110-119 mm Hg, adjusted RR, 1.12; 95% CI, 1.10-1.18, and for 1-SD increase of C-reactive protein among women with diastolic BP 65-74 mm Hg, adjusted RR, 1.14; 95% CI, 1.08-1.20).
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Table 3. Hypertension (Age-Adjusted and Multivariable-Adjusted) by Levels of C-Reactive Protein, According to Baseline Systolic and Diastolic Blood Pressure*
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Overall, there were 7065, 6920, and 6540 women with C-reactive protein levels of less than 1, 1 to less than 3, and 3 or more mg/L, respectively, cut points recently set forth in clinical guidelines.25 For these clinical cut points of C-reactive protein, the RRs of developing hypertension in crude analyses were 1.00, 1.46 (95% CI, 1.36-1.57), and 2.11 (95% CI, 1.97-2.26; linear trend P<.001) respectively; in risk factor–adjusted models, the RRs were 1.00, 1.16 (95% CI, 1.08-1.25), and 1.42 (95% CI, 1.31-1.54; linear trend P<.001) respectively. To evaluate the robustness of the findings among women without major coronary risk factors, we limited analyses to women who were nonsmokers, not using hormone therapy, had a body mass index of less than 30, and did not have diabetes and hypercholesterolemia (n = 6795; 1384 incident cases of hypertension). In this subgroup of women, the age-adjusted RRs were 1.00, 1.26 (95% CI, 1.11-1.42), and 1.69 (95% CI, 1.47-1.94; linear trend P<.001) for corresponding C-reactive protein levels of less than 1, 1 to less than 3, and 3 or more mg/L, respectively. In risk factor–adjusted models, the RRs were 1.00, 1.24 (95% CI, 1.10-1.40), and 1.64 (95% CI, 1.42-1.89; linear trend P<.001) respectively.
To further explore the joint effects of C-reactive protein and BP, we considered clinical cut points of C-reactive protein and its association with hypertension in combination with baseline BP (Figure 1). For systolic BP, a significant statistical interaction with C-reactive protein was observed (P<.001). C-reactive protein levels of 1 to 3 and more than 3 mg/L conferred an additional risk of developing hypertension in women in which systolic BP levels were classified as normal (<120 mm Hg) or prehypertension (<130 mm Hg) by the JNC 7 guidelines, with significant RRs compared with women with a systolic BP of less than 110 mm Hg and C-reactive protein level of less than 1 mg/L (all P<.001). For diastolic BP, a similar additive effect was observed, although the interaction did not reach statistical significance (P = .11).
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Figure. Association Between Increasing Levels of C-Reactive Protein and Systolic and Diastolic Blood Pressure
The multivariable relative risk (95% confidence interval [CI]) of hypertension in 20 525 women with a C-reactive protein (CRP) level of less than 1 mg/L and a systolic blood pressure (BP) of less than 110 mm Hg as the referent, or a CRP level of less than 1 mg/L and a diastolic BP of less than 65 mm Hg as the referent.
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COMMENT
This study provides evidence that baseline levels of C-reactive protein are modestly but independently associated with an increased risk of incident hypertension, even among those with very low initial systolic BP and diastolic BP as classified by the JNC 7.24 This finding for C-reactive protein was independent of baseline levels of systolic BP and diastolic BP. Similar effects were observed among those participants without baseline coronary risk factors and in analyses where C-reactive protein was considered as a continuous variable. These data suggest that inflammation may have a potentially important role in the development of hypertension.
Despite the fact that up to 50 million US individuals are affected,24 the etiology of hypertension often remains unclear. These data from the Women's Health Study represent the first major prospective analysis of the association between C-reactive protein and incident hypertension and are consistent with the findings for other inflammation-sensitive plasma proteins, including fibrinogen,  1-antitrypsin, haptoglobin, orosomucoid, and ceruloplasmin.19 Previous evidence of an association between C-reactive protein and BP has been derived solely from cross-sectional studies in which no causal link can be established.6-9 In those studies, C-reactive protein has been more strongly associated with systolic BP than diastolic BP, which is consistent with the emerging importance of systolic BP as a means of cardiovascular risk prediction.26
Although the current data provide evidence for a critical role of inflammation in the development of hypertension, the mechanisms of this effect are uncertain and require further evaluation. C-reactive protein has been reported to decrease production of nitric oxide by endothelial cells12-13 and thus might indirectly promote vasoconstriction, leukocyte adherence, platelet activation, oxidation, and thrombosis.14-15,27 C-reactive protein also has been reported to have proatherosclerotic properties by upregulating angiotensin type-1 receptor expression,16 affecting the renin-angiotensin system and contributing to the pathogenesis of hypertension. These changes are all indicative of progressive atherosclerosis and endothelial dysfunction,28 with structural and functional changes in the endothelium ultimately leading to the development of hypertension.29 These findings are supported by cross-sectional associations not only for C-reactive protein but also IL-6, intercellular adhesion molecule 1, and tumor necrosis factor with either BP or hypertension.8-9,30
Higher levels of C-reactive protein also play an important role in the induction of plasminogen activator inhibitor 1 (PAI-1), a marker of impaired fibrinolysis and atherothrombosis.15, 31 The recent novel finding that C-reactive protein increases PAI-1 expression and activity in human aortic endothelial cells15 supports a possible mechanism by which the association between C-reactive protein and the development of hypertension is mediated. Patients with hypertension have markedly higher levels of PAI-1 than normotensive patients,32 and both systolic and diastolic BP were significantly (P<.001) and positively associated with PAI-1 levels in the Framingham offspring cohort.33
Potential limitations of our study warrant discussion. As in any epidemiologic study, residual confounding is of concern. After controlling for other known risk factors for both hypertension and atherothrombosis, as well as baseline BP, our results remained significant. We observed similar results in subgroup analyses limited to those participants without baseline coronary risk factors. We relied on a single baseline measurement of C-reactive protein. However, C-reactive protein has been shown to be stable over long periods of follow-up, with little or no diurnal variation.34-35
In our study, incident hypertension was based on self-reported BP, treatment, physician diagnosis, or all 3 combined. To address this potential limitation, we performed a separate study in which an 86% validation rate for self-reported hypertension was observed, consistent with other studies.36-37 For example, in a comparable population in the Nurses' Health Study, 99% of women who reported high BP confirmed their diagnosis based on medical records.37 Sensitivity analyses considering various definitions of hypertension also yielded consistent and significant linear trends across increasing levels of C-reactive protein. Any impact of misclassification would likely be random, biasing our observed RRs toward the null hypothesis.
Although hypertension awareness, treatment, and control rates have increased during the past 3 decades, the identification of individuals at risk for hypertension remains a high priority.24 These data provide evidence that inflammation may be an important mechanism through which hypertension develops.
AUTHOR INFORMATION
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Corresponding Author and Reprints: Howard D. Sesso, ScD, MPH, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, 900 Commonwealth Ave E, Boston, MA 02215-1204 (e-mail: hsesso{at}hsph.harvard.edu).
Author Contributions: Dr Sesso had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Sesso, Blake, Gaziano, Ridker.
Acquisition of data: Buring, Rifai, Gaziano, Ridker.
Analysis and interpretation of data: Sesso, Gaziano, Ridker.
Drafting of the manuscript: Sesso, Ridker.
Critical revision of the manuscript for important intellectual content: Buring, Rifai, Blake, Gaziano, Ridker.
Statistical expertise: Sesso, Gaziano.
Obtained funding: Sesso, Buring, Gaziano, Ridker.
Administrative, technical, or material support: Rifai, Blake, Gaziano, Ridker.
Study supervision: Gaziano, Ridker.
Funding/Support: This study was supported by research grants CA-47988 and HL-43851 from the National Institutes of Health (Bethesda, Md), Scientist Development grant 0130290N from the American Heart Association (Dallas, Tex), with additional support from Pharmacia Inc, the Doris Duke Foundation (New York, NY), the Donald W. Reynolds Foundation (Las Vegas, Nev), and the Leducq Foundation (Paris, France).
Role of the Sponsor: The National Institutes of Health, American Heart Association, Pharmacia, the Doris Duke Foundation, the Donald W. Reynolds Foundation, and the Leducq Foundation did not participate in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.
Acknowledgment: We are grateful to the staff of the Women's Health Study and to the 39 876 dedicated and conscientious female health professionals who are participating in this trial.
Financial Disclosure: Dr Ridker is named as a co-inventor on patents filed by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease and is a Donald W. Reynolds Investigator and receives additional support from the Doris Duke Charitable Foundation and the Leducq Foundation.
Author Affiliations: Department of Medicine, Center for Cardiovascular Disease Prevention and the Division of Preventive Medicine (Drs Sesso, Buring, Blake, Gaziano, and Ridker), and Department of Medicine, Donald W. Reynolds Center for Cardiovascular Research (Drs Sesso, Buring, and Ridker), Brigham and Women's Hospital and Harvard Medical School; Department of Epidemiology, Harvard School of Public Health (Drs Sesso and Buring); and Department of Laboratory Medicine, Children's Hospital and Harvard Medical School (Dr Rifai), Boston, Mass.
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Transforming growth factor-{beta}1 869T/C, but not interleukin-6 -174G/C, polymorphism associates with hypertension in rheumatoid arthritis
Panoulas et al.
Rheumatology (Oxford) 2009;48:113-118.
ABSTRACT
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Uric Acid and Insulin Sensitivity and Risk of Incident Hypertension
Forman et al.
Arch Intern Med 2009;169:155-162.
ABSTRACT
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Association Between Protein-Bound Sialic Acid and High-Sensitivity C-Reactive Protein in Essential Hypertension: A Possible Indication of Underlying Cardiovascular Risk
Sathiyapriya et al.
ANGIOLOGY 2009;59:721-726.
ABSTRACT
Relations of Biomarkers Representing Distinct Biological Pathways to Left Ventricular Geometry
Velagaleti et al.
Circulation 2008;118:2252-2258.
ABSTRACT
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Dyslipidaemia as a predictor of hypertension in middle-aged men
Laaksonen et al.
Eur Heart J 2008;29:2561-2568.
ABSTRACT
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Vascular biomarkers of cognitive performance in a community-based elderly population: the Dublin Healthy Ageing study
Chin et al.
Age Ageing 2008;37:559-564.
ABSTRACT
| FULL TEXT
Hypertension in rheumatoid arthritis
Panoulas et al.
Rheumatology (Oxford) 2008;47:1286-1298.
ABSTRACT
| FULL TEXT
Association of Parental Hypertension With Concentrations of Select Biomarkers in Nonhypertensive Offspring
Lieb et al.
Hypertension 2008;52:381-386.
ABSTRACT
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Relations of Inflammatory Biomarkers and Common Genetic Variants With Arterial Stiffness and Wave Reflection
Schnabel et al.
Hypertension 2008;51:1651-1657.
ABSTRACT
| FULL TEXT
C-Reactive Protein Inhibits Endothelium-Dependent Nitric Oxide-Mediated Dilation of Retinal Arterioles via Enhanced Superoxide Production
Nagaoka et al.
IOVS 2008;49:2053-2060.
ABSTRACT
| FULL TEXT
Tissue Factor and Monocyte Chemoattractant Protein-1 Expression in Hypertensive Individuals with Normal or Increased Carotid Intima-Media Wall Thickness
Sardo et al.
Clin. Chem. 2008;54:814-823.
ABSTRACT
| FULL TEXT
Risk of type 2 diabetes mellitus in those with hypertension: reply
Conen et al.
Eur Heart J 2008;29:953-954.
FULL TEXT
Effect of valsartan compared with valsartan/hydrochlorothiazide on plasma levels of cellular adhesion molecules: the Val-MARC trial
Conen et al.
Heart 2008;94:e13-e13.
ABSTRACT
| FULL TEXT
Effects of Ramipril on Endothelial Function and the Expression of Proinflammatory Cytokines and Adhesion Molecules in Young Normotensive Subjects With Successfully Repaired Coarctation of Aorta A Randomized Cross-Over Study.
Brili et al.
J Am Coll Cardiol 2008;51:742-749.
ABSTRACT
| FULL TEXT
Rationale, Design, and Methodology of the Women's Genome Health Study: A Genome-Wide Association Study of More Than 25 000 Initially Healthy American Women
Ridker et al.
Clin. Chem. 2008;54:249-255.
ABSTRACT
| FULL TEXT
Benefit of Low-Fat Over Low-Carbohydrate Diet on Endothelial Health in Obesity
Phillips et al.
Hypertension 2008;51:376-382.
ABSTRACT
| FULL TEXT
Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease
Tonelli et al.
Circulation 2008;117:163-168.
ABSTRACT
| FULL TEXT
A Prospective Study of Cigarette Smoking and Risk of Incident Hypertension in Women
Bowman et al.
J Am Coll Cardiol 2007;50:2085-2092.
ABSTRACT
| FULL TEXT
Inflammation in the genesis of hypertension and its complications the role of angiotensin II
Li et al.
Nephrol Dial Transplant 2007;22:3107-3109.
FULL TEXT
Relation of Left Ventricular Hypertrophy With Systemic Inflammation and Endothelial Damage in Resistant Hypertension
Salles et al.
Hypertension 2007;50:723-728.
ABSTRACT
| FULL TEXT
Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis
Panoulas et al.
Rheumatology (Oxford) 2007;46:1477-1482.
ABSTRACT
| FULL TEXT
Multimarker Approach to Evaluate the Incidence of the Metabolic Syndrome and Longitudinal Changes in Metabolic Risk Factors: The Framingham Offspring Study
Ingelsson et al.
Circulation 2007;116:984-992.
ABSTRACT
| FULL TEXT
Whole- and refined-grain intakes and the risk of hypertension in women
Wang et al.
Am. J. Clin. Nutr. 2007;86:472-479.
ABSTRACT
| FULL TEXT
Junctional Adhesion Molecule-1 May Have a Wider Role in Cardiovascular Disease
Cheung and Ong
Hypertension 2007;50:e22-e22.
FULL TEXT
C-Reactive Protein and Risk of Breast Cancer
Zhang et al.
JNCI J Natl Cancer Inst 2007;99:890-894.
ABSTRACT
| FULL TEXT
Hypoadiponectinemia as a Predictor for the Development of Hypertension: A 5-Year Prospective Study
Chow et al.
Hypertension 2007;49:1455-1461.
ABSTRACT
| FULL TEXT
C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk: Moving an Inflammatory Hypothesis Toward Consensus
Ridker
J Am Coll Cardiol 2007;49:2129-2138.
ABSTRACT
| FULL TEXT
Diet, Exercise, and C-Reactive Protein Levels in People With Abdominal Obesity: The ATTICA Epidemiological Study
Pitsavos et al.
ANGIOLOGY 2007;58:225-233.
ABSTRACT
Effect of a High-Fiber Diet vs a Fiber-Supplemented Diet on C-Reactive Protein Level
King et al.
Arch Intern Med 2007;167:502-506.
ABSTRACT
| FULL TEXT
Low-Grade Inflammation Is a Risk Factor for Clinical Stroke Events in Addition to Silent Cerebral Infarcts in Japanese Older Hypertensives: The Jichi Medical School ABPM Study, Wave 1
Ishikawa et al.
Stroke 2007;38:911-917.
ABSTRACT
| FULL TEXT
Multiple Biomarkers and the Risk of Incident Hypertension
Wang et al.
Hypertension 2007;49:432-438.
ABSTRACT
| FULL TEXT
Response to Interleukin-6 Antagonists for the Management of Hypertension
Luther and Brown
Hypertension 2007;49:e19-e19.
FULL TEXT
C-Reactive Protein Causes Downregulation of Vascular Angiotensin Subtype 2 Receptors and Systolic Hypertension in Mice
Vongpatanasin et al.
Circulation 2007;115:1020-1028.
ABSTRACT
| FULL TEXT
Age, Blood Pressure, and Retinal Vessel Diameter: Separate Effects and Interaction of Blood Pressure and Age
Kaushik et al.
IOVS 2007;48:557-561.
ABSTRACT
| FULL TEXT
Comparison of Interleukin-6 and C-Reactive Protein for the Risk of Developing Hypertension in Women
Sesso et al.
Hypertension 2007;49:304-310.
ABSTRACT
| FULL TEXT
The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part I: Pathophysiology and Clinical Trial Evidence (Risk Factors Through Stable Coronary Artery Disease)
Dzau et al.
Circulation 2006;114:2850-2870.
FULL TEXT
New-onset hypertension and inflammatory response/poor outcome in acute ischemic stroke
Rodriguez-Yanez et al.
Neurology 2006;67:1973-1978.
ABSTRACT
| FULL TEXT
Genetic Variation Is Associated With C-Reactive Protein Levels in the Third National Health and Nutrition Examination Survey
Crawford et al.
Circulation 2006;114:2458-2465.
ABSTRACT
| FULL TEXT
Positive Association Between Plasma Fibrinogen Level and Incident Hypertension Among Men: Population-Based Cohort Study
Shankar et al.
Hypertension 2006;48:1043-1049.
ABSTRACT
| FULL TEXT
Inflammation and Atherothrombosis: From Population Biology and Bench Research to Clinical Practice
Libby and Ridker
J Am Coll Cardiol 2006;48:A33-A46.
ABSTRACT
| FULL TEXT
Quantitative trait locus on chromosome 20q13 for plasma levels of C-reactive protein in healthy whites: the HERITAGE Family Study
Lakka et al.
Physiol. Genomics 2006;27:103-107.
ABSTRACT
| FULL TEXT
The search for a link between inflammation and hypertension--contribution from Bartter's/Gitelman's syndromes
Pagnin et al.
Nephrol Dial Transplant 2006;21:2340-2342.
FULL TEXT
C-Reactive Protein Is an Intermediate Step Between Obesity and Hypertension--Reply
Lakoski et al.
Arch Intern Med 2006;166:1527-1527.
FULL TEXT
C-Reactive Protein in Hypertensive Disorders in Pregnancy
Paternoster et al.
CLIN APPL THROMB HEMOST 2006;12:330-337.
ABSTRACT
C-reactive protein in atherosclerosis: A causal factor?
Paffen and deMaat
Cardiovasc Res 2006;71:30-39.
ABSTRACT
| FULL TEXT
Valsartan, Blood Pressure Reduction, and C-Reactive Protein: Primary Report of the Val-MARC Trial
Ridker et al.
Hypertension 2006;48:73-79.
ABSTRACT
| FULL TEXT
Novel anti-inflammatory drugs in hypertension
Hermann and Ruschitzka
Nephrol Dial Transplant 2006;21:859-864.
FULL TEXT
Inflammation and hypertension: the search for a link
Pauletto and Rattazzi
Nephrol Dial Transplant 2006;21:850-853.
FULL TEXT
C-Reactive Protein and Metabolic Syndrome in Elderly Women: A 12-year follow-up study
Hassinen et al.
Diabetes Care 2006;29:931-932.
FULL TEXT
Metabolic Syndrome and the Risk of Stroke in Middle-Aged Men
Kurl et al.
Stroke 2006;37:806-811.
ABSTRACT
| FULL TEXT
C-Reactive Protein Concentration and Incident Hypertension in Young Adults: The CARDIA Study.
Lakoski et al.
Arch Intern Med 2006;166:345-349.
ABSTRACT
| FULL TEXT
Endothelin-1 expression in vascular adventitial fibroblasts
An et al.
Am. J. Physiol. Heart Circ. Physiol. 2006;290:H700-H708.
ABSTRACT
| FULL TEXT
C-reactive protein in patients with COPD, control smokers and non-smokers
Pinto-Plata et al.
Thorax 2006;61:23-28.
ABSTRACT
| FULL TEXT
Cost-Effectiveness of Ambulatory Blood Pressure: A Reanalysis
Krakoff
Hypertension 2006;47:29-34.
ABSTRACT
| FULL TEXT
A Prospective Study of Plasma Lipid Levels and Hypertension in Women
Sesso et al.
Arch Intern Med 2005;165:2420-2427.
ABSTRACT
| FULL TEXT
Effect of exercise training on plasma levels of C-reactive protein in healthy adults: the HERITAGE Family Study
Lakka et al.
Eur Heart J 2005;26:2018-2025.
ABSTRACT
| FULL TEXT
Insulin Resistance and Hypertension: The Chicken-Egg Question Revisited
Hu and Stampfer
Circulation 2005;112:1678-1680.
FULL TEXT
Incidence of Myocardial Infarction and Death in Relation to Walking-Induced Calf Pain and Plasma Levels of Inflammation-Sensitive Proteins
Lind et al.
ANGIOLOGY 2005;56:507-516.
ABSTRACT
Association of C-Reactive Protein With Blood Pressure
Bautista et al.
Arterioscler. Thromb. Vasc. Bio. 2005;25:e137-e138.
FULL TEXT
Risk of hypertension and reduced kidney function after acute gastroenteritis from bacteria-contaminated drinking water
Garg et al.
CMAJ 2005;173:261-268.
ABSTRACT
| FULL TEXT
C-Reactive Protein and Electrocardiographic ST-Segment Depression Additively Predict Mortality: The Strong Heart Study
Okin et al.
J Am Coll Cardiol 2005;45:1787-1793.
ABSTRACT
| FULL TEXT
Longitudinal study of soy food intake and blood pressure among middle-aged and elderly Chinese women
Yang et al.
Am. J. Clin. Nutr. 2005;81:1012-1017.
ABSTRACT
| FULL TEXT
Association of C-Reactive Protein With Blood Pressure and Hypertension: Life Course Confounding and Mendelian Randomization Tests of Causality
Smith et al.
Arterioscler. Thromb. Vasc. Bio. 2005;25:1051-1056.
ABSTRACT
| FULL TEXT
C-reactive protein does not relax vascular smooth muscle: effects mediated by sodium azide in commercially available preparations
Swafford et al.
Am. J. Physiol. Heart Circ. Physiol. 2005;288:H1786-H1795.
ABSTRACT
| FULL TEXT
Low-Grade Albuminuria and the Risks of Hypertension and Blood Pressure Progression
Wang et al.
Circulation 2005;111:1370-1376.
ABSTRACT
| FULL TEXT
C-Reactive Protein Levels Are Not Associated with Increased Risk for Colorectal Cancer in Women
Zhang et al.
ANN INTERN MED 2005;142:425-432.
ABSTRACT
| FULL TEXT
Arterial Stiffness and Hypertension: A Two-Way Street?
Franklin
Hypertension 2005;45:349-351.
FULL TEXT
Low-Grade Inflammation and Microalbuminuria in Hypertension
Pedrinelli et al.
Arterioscler. Thromb. Vasc. Bio. 2004;24:2414-2419.
ABSTRACT
| FULL TEXT
Inflammation, Abdominal Obesity, and Smoking as Predictors of Hypertension
Niskanen et al.
Hypertension 2004;44:859-865.
ABSTRACT
| FULL TEXT
Retinal Arteriolar Narrowing Is Associated With 5-Year Incident Severe Hypertension: The Blue Mountains Eye Study
Smith et al.
Hypertension 2004;44:442-447.
ABSTRACT
| FULL TEXT
Hypertensive Response to Acute Stress Is Attenuated in Interleukin-6 Knockout Mice
Lee et al.
Hypertension 2004;44:259-263.
ABSTRACT
| FULL TEXT
Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation
Fliser et al.
Circulation 2004;110:1103-1107.
ABSTRACT
| FULL TEXT
From bedside to bench to bedside: role of renin-angiotensin-aldosterone system in remodeling of resistance arteries in hypertension
Schiffrin and Touyz
Am. J. Physiol. Heart Circ. Physiol. 2004;287:H435-H446.
FULL TEXT
Should C-Reactive Protein Be Added to Metabolic Syndrome and to Assessment of Global Cardiovascular Risk?
Ridker et al.
Circulation 2004;109:2818-2825.
ABSTRACT
| FULL TEXT
Other articles noted
Evid. Based Med. 2004;9:63-64.
FULL TEXT
Link Between Elevated CRP and Incident Hypertension
Journal Watch Cardiology 2004;2004:3-3.
FULL TEXT
Is Hypertension an Inflammatory Condition?
JWatch General 2004;2004:3-3.
FULL TEXT
Cardiovascular News
SoRelle
Circulation 2003;108
:e9079-e9080.
FULL TEXT
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