The Pennsylvania State University The Graduate School College of Health and Human Development EFFECTS OF CAFFEINE, STRESS, AND FAMILY HISTORY OF HYPERTENSION ON BLOOD PRESSURE AND BLOOD MARKERS OF CARDIOVASCULAR DISEASE RISK A Thesis in Biobehavioral Health by Isabella M. Rodrigues © 2005 Isabella M. Rodrigues Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy December 2005 ii The thesis of Isabella M. Rodrigues was reviewed and approved* by the following: Laura Cousino Klein Associate Professor of Biobehavioral Health Thesis Advisor Chair of Committee Frank M. Ahern Senior Research Associate Department of Biobehavioral Health Lynn T. Kozlowski Professor of Biobehavioral Health Head of the Department of Biobehavioral Health Robert M. Stern Distinguished Professor of Psychology *Signatures are on file in the Graduate School iii ABSTRACT Cardiovascular disease has been the leading cause of death in the United States since 1918. A number of studies have investigated the connection between caffeine, primarily through coffee, and its potentially detrimental effects on cardiovascular health. The vast majority of such investigations have been focused on blood cholesterol, while other blood markers of cardiovascular disease such as fibrinogen and C-reactive protein and their relationship with caffeine has been vastly understudied. A large number of studies have reported that both fibrinogen and C-reactive protein can be useful predictors of future cardiovascular disease, but their relationship with caffeine remains unknown. Furthermore, to this date, no published studies have reported on the effects of psychological stress on these blood markers, either alone, or in combination with caffeine, and no gender differences have been reported. The current study examined the effects of caffeine and psychological stress on a population particularly vulnerable to future development of cardiovascular disease, those with a parental history of hypertension. This study used a 2 (gender; 26 men, 26 women) X 2 (drug condition; 26 no caffeine, 26 3.3mg/kg caffeine) experimental design. Participants came to a initial screening session where blood was drawn for a cholesterol assessment and extensive health screening to ensure that all participants were healthy. Qualified participants then completed a 3.5 hour experimental session to examine stress reactivity to caffeine or no caffeine exposure. Blood pressure and heart rate were collected during the experimental session, as well as 3 blood samples at baseline, stress, and recovery for later assessment of cortisol, C-reactive protein (CRP) and fibrinogen levels, and, for females, progesterone and estradiol to confirm luteal phase cycle status. Findings from this study revealed increases in fibrinogen levels in response to caffeine, but no significant CRP changes. However, significant increase in CRP levels were observed when post-hoc analyses were conducted that involved the grouping of participants into low, moderate, and high CRP risk group based on baseline CRP levels. Systolic blood pressure significantly increased in males and females in response to both the stressor and caffeine. Diastolic blood pressure and heart rate significantly increased in males and females in response to the stressor, but not in response to caffeine. Implications of these findings are discussed, as well as methodological differences between this dissertation project and previous research. Suggestions for future studies and the contribution of the current study to the literature are presented. iv TABLE OF CONTENTS LIST OF FIGURES .....................................................................................................ix LIST OF TABLES.......................................................................................................xiii ACKNOWLEDGEMENTS.........................................................................................xiv CHAPTER 1: INTRODUCTION................................................................................1 Scope of the Problem............................................................................................1 Blood Markers of Cardiovascular Health.............................................................3 Cholesterol.....................................................................................................3 Fibrinogen......................................................................................................5 C-Reactive Protein (CRP) .............................................................................7 Summary........................................................................................................11 Caffeine, Cholesterol, and Triglycerides..............................................................11 Early findings ................................................................................................11 Epidemiological studies examining the relationship between coffee and blood lipids.............................................................................................12 Potential mechanisms that contribute to the relationship between coffee consumption and cholesterol levels: Human studies..............................16 Potential mechanisms that contribute to the relationship between coffee consumption and cholesterol levels: Animal studies .............................23 Coffee oil diterpenes’ effects on cholesterol: Cafestol and kahweol ............26 v Additional biobehavioral factors that may contribute to the effects of caffeine on cholesterol and cardiovascular disease................................30 Genetic influences..................................................................................30 Sex differences .......................................................................................33 Tobacco smoking ...................................................................................34 Caffeine and coffee effects on fibrinogen .....................................................36 Caffeine, coffee, and CRP levels...................................................................37 Conclusions ...................................................................................................38 CHAPTER 2: EXPERIMENT.....................................................................................45 Overview...............................................................................................................45 Hypotheses............................................................................................................45 Methods ................................................................................................................52 Participants. ...................................................................................................52 Recruitment. ..................................................................................................52 Exclusionary criteria......................................................................................53 Family History of hypertension selection......................................................55 Protocol.................................................................................................................56 Cholesterol screening session........................................................................56 Drug...............................................................................................................58 Laboratory session.........................................................................................58 Baseline. ........................................................................................................59 vi Stress protocol. ..............................................................................................60 Blood collection and storage. ........................................................................62 CHAPTER 3: RESULTS.............................................................................................65 Stressor and Caffeine Administration Confirmation ............................................65 Self-report measures......................................................................................65 Serum cortisol................................................................................................67 Blood Markers of Cardiovascular Disease Risk...................................................68 Fibrinogen......................................................................................................68 C-Reactive protein.........................................................................................69 Blood pressure and Heart Rate .............................................................................70 Systolic blood pressure..................................................................................71 Diastolic blood pressure ................................................................................71 Heart rate .......................................................................................................72 Post-Hoc CRP Analyses: CRP Risk Group..........................................................72 Summary of Hypotheses.......................................................................................76 CHAPTER 4: GENERAL DISCUSSION...................................................................104 Overview...............................................................................................................104