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CARDIOVASCULAR

RISK FACTORS

Edited by Armen Yuri Gasparyan

Cardiovascular Risk Factors

Edited by Armen Yuri Gasparyan

Published by InTech

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Copyright © 2012 InTech

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First published March, 2012

Printed in Croatia

A free online edition of this book is available at www.intechopen.com

Additional hard copies can be obtained from [email protected]

Cardiovascular Risk Factors, Edited by Armen Yuri Gasparyan

p. cm.

ISBN 978-953-51-0240-3

Contents

Preface IX

Chapter 1 Cardiovascular Risk Investigation: When Should It Start? 1

Anabel Nunes Rodrigues, Gláucia Rodrigues de Abreu

and Sônia Alves Gouvêa

Chapter 2 Early Identification of Cardiovascular

Risk Factors in Adolescents and

Follow-Up Intervention Strategies 17

Heather Lee Kilty and Dawn Prentice

Chapter 3 Novel and Traditional Cardiovascular

Risk Factors in Adolescents 61

Alice P.S. Kong and Kai Chow Choi

Chapter 4 Cardiovascular Risk Factors in the Elderly 81

Melek Z. Ulucam

Chapter 5 Vascular Inflammation: A New Horizon

in Cardiovascular Risk Assessment 103

Vinayak Hegde and Ishmael Ching

Chapter 6 Alterations in the Brainstem Preautonomic

Circuitry May Contribute to Hypertension

Associated with Metabolic Syndrome 141

Bradley J. Buck, Lauren K. Nolen, Lauren G. Koch,

Steven L. Britton and Ilan A. Kerman

Chapter 7 Cardiometabolic Syndrome 161

Alkerwi Ala’a, Albert Adelin

and Guillaume Michèle

Chapter 8 Relationship Between Cardiovascular Risk Factors

and Periodontal Disease: Current Knowledge 193

Sergio Granados-Principal, Nuri El-Azem,

Jose L. Quiles, Patricia Perez-Lopez,

Adrian Gonzalez and MCarmen Ramirez-Tortosa

VI Contents

Chapter 9 Cardiovascular Risk Assessment

in Diabetes and Chronic Kidney Diseases:

A New Insight and Emerging Strategies 217

Ali Reza Khoshdel

Chapter 10 Non Invasive Assessment of Cardiovascular

Risk Profile: The Role of the Ultrasound Markers 251

Marco Matteo Ciccone, Michele Gesualdo,

Annapaola Zito, Cosimo Mandurino,

Manuela Locorotondo and Pietro Scicchitano

Chapter 11 Endothelial Progenitor Cell Number:

A Convergence of Cardiovascular Risk Factors 265

Michel R. Hoenig and Frank W. Sellke

Chapter 12 Nitric Oxide Signalling in

Vascular Control and Cardiovascular Risk 279

Annette Schmidt

Chapter 13 An Anti-Inflammatory Approach in

the Therapeutic Choices for

the Prevention of Atherosclerotic Events 301

Aldo Pende and Andrea Denegri

Chapter 14 Gender-Specific Aspects in the Clinical

Presentation of Cardiovascular Disease 327

Chiara Leuzzi, Raffaella Marzullo, Emma Tarabini Castellani

and Maria Grazia Modena

Chapter 15 The Role of Stress in a Pathogenesis of CHD 337

Taina Hintsa, Mirka Hintsanen,

Tom Rosenström and Liisa Keltikangas-Järvinen

Chapter 16 Pulse Pressure and Target Organ Damage 365

Adel Berbari and Abdo Jurjus

Chapter 17 Low-Level Exposure to

Lead as a Cardiovascular Risk Factor 387

Anna Skoczynska and Marta Skoczynska

Chapter 18 Obstructive Sleep Apnoea Syndrome

as a Systemic Low-Grade Inflammatory Disorder 411

Carlos Zamarrón, Emilio Morete and Felix del Campo Matias

Chapter 19 New Cardiovascular Risk

Factors and Physical Activity 433

Nicolás Terrados and Eduardo Iglesias-Gutiérrez

Contents VII

Chapter 20 Dietary Supplements and Cardiovascular Disease: What

is the Evidence and What Should We Recommend? 449

Satoshi Kashiwagi and Paul L. Huang

Chapter 21 Mediterranean Diet and Cardiovascular Risk 465

Javier Delgado-Lista, Ana I. Perez-Caballero,

Pablo Perez-Martinez, Antonio Garcia-Rios,

Jose Lopez-Miranda and Francisco Perez-Jimenez

Preface

An Insight on Cardiovascular Risk Factors: Challenges and

Opportunities

Our understanding of the implications of cardiovascular risk factors has greatly

improved over the past two decades. It has been postulated that numerous risk factors

and markers of inflammation and immune response trigger pathologic changes in the

vascular wall from early life, leading to atherosclerotic cardiovascular disease in later

life [1]. It has also been widely recognized that no single risk factor causes

atherosclerotic disease, and that the likelihood of the disease depends on a

multifactorial genetic and environmental background. The complex nature of risk

factors and their interdependence implies the need of multidirectional preventive

measures, which should be monitored and assessed with the use of multiple

demographic, clinical, genetic and laboratory parameters.

Over the past decades, the dominating concept of cardiovascular prevention has been

based on the initial results of the landmark Framingham Heart Study, which linked

the burden of cardiovascular disease with a combination of traditional risk factors,

such as age, sex, arterial hypertension, hyperlipidemia, smoking, obesity, diabetes, and

sedentary lifestyle. The study led to the validation and wide-spread use of the

Framingham Risk Score, which is an indispensable tool for stratifying cardiovascular

risk and treatment by clinicians and deploying strategies for community-based

primary preventive measures by health administrators [2, 3].

The decades-long application of the Framingham Risk Score in different populations

worldwide has also revealed its inherent limitations and led to the development of

several alternative tools (e.g., SCORE [Systematic Coronary Risk Evaluation],

Reynolds Risk Score, QRISK [QRESEARCH Cardiovascular Risk Algorithm]) [4].

Though the new tools have addressed some problems, none of these has been

universally accepted, raising concerns over ethnicity, psychosocial background,

comorbidities, drug therapies, and validity of biomarkers incorporated in the risk

scores. For example, a recent large study showed that currently available risk scores

do not provide precise estimates of cardiovascular risk in patients with rheumatoid

arthritis [5], leaving the issue of risk-score-based cardiovascular prevention in this

particular population uncertain. The guidance based on cardiovascular risk scores in

patients with inflammatory disorders may either underestimate, which is more likely,

X Preface

or overestimate the real risk. Given the results of statistical analyses in large cohorts,

an attempt was made to correct values of risk scores in patients with rheumatoid

arthritis by using a 1.5 multiplier [6]. In practice, however, the latter approach was not

regarded as realistic [7], necessitating more research into cardiovascular

pathophysiology and therapies in inflammatory disorders.

There are still many uncertainties over the interaction between traditional and novel

risk factors leading to premature cardiovascular morbidity and mortality in the

general population and in patients with diseases predisposing to vascular damage and

accelerated atherothrombosis. Systemic inflammation has long been regarded as a

crucial factor of premature cardiovascular disease. Initial evidence for this stems from

the Physicians’ Health Study [8], which highlighted the significance of subclinical

inflammation and slight elevation of C-reactive protein (CRP) level undetectable by

conventional laboratory tests. A more recent large trial, the Justification for Use of statins

in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), reaffirmed that

the suppression of low-grade inflammation (CRP just above 2 mg/l) can bring benefits in

terms of primary cardiovascular prevention in the general population [9]. The JUPITER

study also proved that the greatest cardiovascular risk reduction as a result of

antiinflammatory therapy with rosuvastatin is expected in subjects with the highest

levels of CRP. Whether the same or even greater risk reduction can be derived in high￾and low-grade inflammatory disorders and whether statins can occupy their niche in the

combined treatment of the patients are still a matter of debate, which may be resolved

once the results of specifically designed and powered trials become available [10-12].

Several lines of evidence, mainly derived from retrospective cohort studies, suggest

that systemic inflammation drives atherogenesis in cohorts of patients with systemic

lupus erythematosus (SLE) and rheumatoid arthritis (RA). The exposure to high-grade

inflammation is a crucial pathogenic factor in these patients, justifying aggressive

antiinflammatory treatment, which, in turn, proved to reduce atherosclerotic burden

among other disease-modifying effects [13-15]. The link between inflammation and

atherosclerotic cardiovascular disease, however, is not universally evident across

cohorts of patients with inflammatory disorders [16]. A recent systematic review on

vascular function in RA revealed discrepancies across numerous cross-sectional and

longitudinal studies, and questioned the direct link between rheumatoid inflammation

and vasculopathy [17]. Moreover, numerous studies of varying levels of evidence

suggested the lack of association between persistent low-grade inflammation and

atherosclerotic vascular disease in patients with systemic vasculitides, including those

with Wegener granulomatosis [18] and Behçet disease (BD) [19], the latter viewed as a

model of venous thrombosis [20]. Obviously, the reported discrepancies indicate the

complexity of atherogenic pathways and warrant further research into novel

cardiovascular risk markers.

Over the past decade, several promising markers of inflammation-mediated

atherosclerosis have emerged. Of these, markers of activated platelets, such as platelet￾bound P-selectin, CD40 ligand, beta-thromboglobulin, platelet factor 4, platelet-

Preface XI

derived microparticles, as well as platelet count and size have been tested in the

general population, in cohorts of patients with RA and some other inflammatory

disorders in association with cardiovascular risk factors and vascular end-points [21-

23]. Mean platelet volume was shown to be a readily available, well-standardized

marker of inflammation and thrombosis predictive of atherosclerotic vascular end￾points in some well-designed retrospective and prospective cohort studies [24].

Furthermore, a suggestion was made to routinely assess mean platelet volume and a

set of other markers of platelet activation and their genetic variability to guide

antiplatelet therapies and overall cardiovascular prevention [25].

With the advent of noninvasive vascular imaging tools, our understanding of the

mechanisms of accelerated atherosclerosis has further deepened. The availability of

standardized ultrasound techniques for assessing flow-mediated dilation of the

brachial artery, intimal-medial thickness (IMT) and atherosclerotic plaques in the

common carotid artery holds particular promise for instrumental diagnostics of

macrovascular pathology and prediction of vascular events across populations of

healthy subjects and patients [26, 27]. Most notably, the largest ARIC (Atherosclerosis

Risk in Communities) study involving 13,145 subjects proposed a new model for

prediction of 10-year coronary heart disease risk, best assessed when carotid IMT and

plaques added to the traditional cardiovascular risk factors model [28]. A recent meta￾analysis, based on 22 retrospective cohort studies, proved the increase of carotid IMT

in RA patients and affirmed the use of IMT for evaluation of cardiovascular burden in

this population of patients [29]. Finally, the latest prospective cohort study with 64 RA

patients, followed up for a mean of 3.6 years, revealed an association of traditional

cardiovascular risk factors and low-dose corticosteroids, but not systemic inflammation

with plaque formation [30]. These data coupled with a comparative study of IMT and

atherosclerotic plaques in patients with SLE or familial Mediterranean fever [31], shed

light on the interactions of cardiovascular and inflammation-mediated risk factors in the

process of atherogenesis, and may suggest the use of noninvasive markers of carotid

alterations for modelling cardiovascular risk across populations of healthy subjects and

those with low- and high-grade inflammatory disorders.

Some other tools for cardiovascular risk prediction are now under evaluation. Of these,

coronary artery calcium score assessed by multi-detector computed tomography seems

particularly useful for primary cardiovascular predictive models and for stratifying

patients in the emergency setting [32]. Another promising technique is intravascular

ultrasound employed by invasive cardiologists for detecting vulnerable atherosclerotic

plaques and guiding pharmacotherapy and invasive procedures in cardiovascular

disease [33]. Though these techniques allow more precise evaluation of atherosclerotic

burden, their wide-spread use for community-based cardiovascular prevention is limited

owing to the narrow scope of implications, financial concerns, and invasive nature.

Overall, recent advances in understanding of sophisticated pathways of atherogenesis

and the emergence of a multitude of laboratory and instrumental markers of

atherosclerosis are seemingly shifting preventive and therapeutic strategies toward

XII Preface

multi-dimentional and more personalized approaches. Better equipped and well

supplied by old and new cardiovascular drugs communities as well as cardiological

and general internal medicine units are now required to comprehensively evaluate

cardiovascular risk and closely monitor efficiency of cardiovascular prevention. As a

prime example, the efficiency of preventive use of an old drug, acetyl salicylic acid, is

now known to be dependent on the physicians and patients’ adherence to its

administration as well as on the correction of low-grade inflammation and comorbid

conditions which may attenuate the clinical implications of the therapy [34, 35]. In

addition, the elucidation of a wide range of pleiotropic effects of statins and the strong

evidence favoring their use for primary and secondary prevention, particularly in

conditions associated with systemic inflammation (based on the data from the

JUPITER trial), have reserved a place for this class of drugs next to acetyl salicylic acid,

angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and

beta-blockers in the schemes of combined therapies of cardiovascular disease. More

recent studies, however, tapered some of the enthusiasm with the universal

applicability of statins, owing to the lack of benefit and risk of adverse effects, such as

liver and kidney dysfunction, myopathy, and cataract, particularly in high-risk groups

of patients, such as those with heart failure and kidney disease [36, 37]. Finally, the

rationale for a more differentiated approach to cardiovascular prevention by different

drugs of the same class has recently been appreciated thanks to the evidence from the

landmark HOPE (Heart Outcomes Prevention Evaluation) and ONTARGET (The

Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial)

trials suggesting that among numerous ACE inhibitors and angiotensin II receptor

blockers only ramipril and telmisartan bring most benefits of cardiovascular

protection in high-risk populations of patients [38].

Undoubtedly, knowledge of cardiovascular risk factors has greatly advanced over the

past decades. Old dogmas over cholesterol as the only target of cardiovascular

prevention have been replaced by theories supporting the diversity of atherosclerotic

pathways and the need for combined and personalized interventions. The modern

armamentarium of cardiovascular prevention is enriched with the abundance of

efficacious nonpharmacological and pharmacological means. Many more are still

subject of large-scale research studies, and initiatives are underway to bring more

benefits and better care for the population-at-large.

Armen Yuri Gasparyan and

George D. Kitas

Department of Rheumatology, Clinical Research Unit,

Dudley Group NHS Foundation Trust

(A Teaching Trust of University of Birmingham),

Russell's Hall Hospital,

Dudley, West Midlands DY1 2HQ,

United Kingdom

Preface XIII

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Preface XV

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