Journal of Cardiovascular Disease Research An Official Publication of SciBiolMed.Org (A publishing division of Phcog.Net)

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1 ISSN: Journal of Cardiovasular Disease Researh An Offiial Publiation of SiBiolMed.Org (A publishing division of Phog.Net) Our mission, Your Outstanding Researh Work Volume 7, Issue 2, Apr-Jun, 2016 About Journal Journal of Cardiovasular Disease Researh (J Cardiovas. Dis. Res.) [ [ISSN: Print , Online ] An offiial publiation of Sibiolmed.Org ( it is a double-blind peer-reviewed, open aess international irulating professional journal led by a group of researh sientists, vasular disease experts and ardiologists oming from North Ameria, Asia and Europe et. Indexed and Abstrated in : The journal is indexed with Caspur, Chemial Abstrats, CNKI (China National Knowledge Infrastruture), DOAJ, EBSCO Publishing's Eletroni Databases, Expanded Aademi ASAP, Genamis JournalSeek, Google Sholar, Health & Wellness Researh Center, Health Referene Center Aademi, Hinari, Index Copernius, MANTIS, OpenJGate, PrimoCentral, ProQuest, Simago Journal Ranking, SCOLOAR, SCOPUS, SIIC databases, Summon by Serial Solutions and Ulrih's International Periodial Diretory JCDR - Providing Cutting Edge Researh information on Cardiovasular Diseases Senior International Editor: Dr. Dayi Hu Editor : Dr. Peng Zhou

2 J Cardiovas Disease Res., 2016; 7(2): A Multifaeted Peer Reviewed Journal in the field of Cardiology Original Artile Castelli Index and estimative of LDL- partile size may still help in the linial pratie? Sandra Maria Barbalho 1, Riardo José Tofano 2, Marelo Dib Behara 1, Karina Quesada 1, Daniel Pereira Coqueiro 3, Claudemir Gregório Mendes 1 1 Department of Biohemistry and Celular Biology Medial Shool of Marília UNIMAR, Av. Higino Muzzi Filho 1001, Marília, São Paulo, BRAZIL. 2 Medial Dotor, Cardiologist of the Cardia Surgery Unit and Hemodynamis - Medial Shool, Av. Higino Muzzi Filho 1001, Marília, São Paulo, BRAZIL. 3 Professor at Fauldade de Ensino Superior do Interior Paulista - FAIP - Marília, SP, Brazil and PhD student at Unifesp, São Paulo, BRAZIL. ABSTRACT Bakground: There are many fators affeting the maintenane of a healthy in the population without oronary artery disease as plasmati lipids and anthropometri parameters. This study aimed to evaluate the orrelation between the Castelli Index I, Castelli Index II and the estimated size of the LDL- partile with the presene of Coronary Artery Disease risk fators in patients undergoing oronary angiography. Methods: Anthropometri (waist irumferene and body mass index) and biohemial parameters (glyaemia, total holesterol, triglyerides, LDL-, HDL- and high sensitivity C-reative protein) from 95 patients undergoing oronary arteriography were olleted. Castelli Index I (TC/HDL-), Castelli Index II (LDL-/HDL-) and the estimate of LDL partile size (TG/HDL-) were alulated. Results: Our findings show that, in general, for abnormal values of the three rations ited above, there was a positive orrelation with inreased levels of serum lipids and that there are high perentages of subjets with inreased values of WC, BMI and hscrp and also the presene of MS, physial inativity and family story of heart disease. Most patients with severe lesions in the arteries presented altered Castelli Index II and small dense LDL- partile. Conlusion: The use of these tree ratios may represent simple parameters for estimating ardiovasular risks patients with heart disease diagnosis in order to work on seondary prevention. Key words: HDL-, LDL-, Triglyerides, Total Cholesterol, Coronary Angiography. Correspondene: Sandra Maria Barbalho Department of Biohemistry, Medial Shool of Marília, UNIMAR, Av. Higino Muzzi Filho 1001, Marília, SP, BRAZIL. Phone: Submission Date: ; Review ompleted: ; Aepted Date: smbarbalho@gmail.om DOI : /jdr INTRODUCTION Cardiovasular disease (CAD) is a serious publi health problem in both sexes worldwide. It is strongly assoiated to the Metaboli Syndrome (MS) that omprises a number of risk fators that plays a fundamental role in high morbidity. MS is usually manifested by insulin resistane and modifiations in the referene ranges HDL- and triglyerides (TG), waist irumferene (WC), blood pressure, C-reative protein (CRP) and obesity. This last ondition is haraterized by high levels of pro inflammatory mediators. 1 3 Plasma lipids play diret importane in the prevention of ardiovasular omorbidities. As a result, they have beome therapeuti targets for minimizing the potential risks. Dyslipidemia is assoiated with redued HDL- levels and LDL- partile size. The small dense LDL- partiles (sdldl-) are related to the formation of atherosleroti plaques beause of the redution of the affinity with the LDL- reeptor and inreased possibility of being inorporated in the intima of the vessel. Some authors have been using the Castelli Index I and II index (whih respetively relate to the ratio Total Cholesterol (TC/HDL- and LDL-/HDL-) in addition to estimate of LDL- partiles (TG/HDL-) to assist in the assessment of ardiovasular risk. 1,4-9 The biomarkers have been extensively studied as potential CAD risk fators and an be onsidered in the linial stratifiation of these diseases. Calulated indexes obtained from laboratory measurements and the evaluation of plasma biomarkers are ommonly used in CAD risk assessment. 10 Based on these assumptions, this study aimed to evaluate the orrelation between the Castelli Index I (CI-I), Castelli Index II (CI-II) and the estimated size of the LDL- partile with the presene of CAD risk fators in patients undergoing oronary angiography. METHODS Ethial Priniples This study was approved by the Ethis Committee of the University of Marilia (Protool 449/Reord / ) and began only after the partiipants signed a Free and Informed Consent Form (Resolution 196/10 of Otober 1996 National Health Counil CNS). The proedures used during the experimental protool followed the ethial standards of the Institutional Ethis Committee and the Helsinki Delaration of 1975, revised in Subjets: data olletion The patients were 54 men and 43 women (aged from 36 to 88 years old) undergoing oronary arteriography. After signing the Free and Informed Consent, they answered a questionnaire on soioeonomi data, family history of CAD, smoking and alohol habits, physial ativity and use of statin. Blood pressure (BP), waist irumferene (WC) and body mass index (BMI) were also evaluated. Blood was obtained to determine glyaemia, triglyerides (TG), total holesterol (TC), low-density lipoprotein holesterol (LDL-), highdensity lipoprotein holesterol (HDL-) and hs-crp (high sensitivity C-reative protein). The blood was drawn when the patient was already atheterized for the angiography proedure. The exams were performed after the protool of the São Franiso Laboratory at the University Journal of Cardiovasular Disease Researh, Vol 7, Issue 2, Apr-Jun,

3 Hospital, University of Marilia, SP, Brazil and the results followed Lloyd- Jones et al. 11 The indexes were alulated as follows: TC/HDL- (CI-I) and LDL-/ HDL- (CI-II) that advoates normal values respetively when less than 4.4 and 2.9. The estimate of LDL- partile size (TG/HDL-) should be higher than 2 mg/dl. 4 Statistis Our results were analyzed with the statistial program R version Qualitative variables were obtained by alulating the absolute and relative frequenies. We used Pearson s hi-square test and Fisher s exat test or its extension for omparison of the ategorial variables. A level of signifiane α of 5% was applied to all the onlusions obtained from the inferential analysis. RESULTS Values for IC-I and IC-II were onsidered altered when higher than, respetively 4.4 and 2.9. The estimate of LDL- partile size was onsidered altered when smaller than 2 mg/dl. There were statistially signifiant differenes between subjets lassified as normal and altered CI-I (Table 1) for family story of heart, LDL-, TG and onsequently for TC and HDL-. It is also possible to observe that subjets with inreased WC, sedentary, without using statin, with severe lesion in the atheterization report and with MS represented high perentages of altered CI-I. Table 2 shows signifiant differenes between the group with altered and normal values for CI-II only for family story of heart, total holesterol levels, LDL- and HDL-. However, we an see that subjets with inreased WC, BMI and hscrp, with presene of MS, who do not exerise and do not use statin and with severe lesion in the atheterization report present high perentage of altered CI-II. In Table 3 we an observe that signifiant differenes only for the presene of hypertension, atheterization report (the most serious injuries predominated in individuals with altered TG/HDL-) and to the levels of HDL- and LDL-. It is important to point that patients with inreased WC and hscrp levels and who have MS, do not exerise or use statin were lassified as possessing sdldl- partile. Subjets with smoking habits are more likely to exhibit altered values for CI-I, CI-II and sdldl-. DISCUSSION Several fators may influene the ourrene of ardiovasular disease (CAD) as smoking, obesity, physial inativity, high levels of total holesterol and low levels of HDL-, high blood pressure and insulin resistane. These fators aount for 61% of CAD deaths and more than 75% of deaths resulting from ishemi and hypertensive heart diseases There is a onsensus in the literature that the management of hyperlipidemia should be done in order to prevent CAD but many doubts about the assoiation of the lipids have yet to be solved. As pointed before, CI-I and CI-II and the ratio TG/HDL- may assist in vasular risk assessment sine they are important preditors of aute myoardial infartion. The presene of sdldl- is related to the development of atherogenesis due to its low affinity for LDL- reeptors and greater suseptibility to peroxidation. 4,5,7,8,14,15 Our results show that, in general, for abnormal values of the three ratios ited above, there was a positive assoiation with inreased levels of serum lipids and that there are high perentages of subjets with inreased WC, BMI and hscrp and also the presene of MS, physial Table 1: Charateristis of the patients, aording to TC/HDL- (Castelli Index I) TC/HDL- Waist irunferene high % % normal % % Physial ativity praties yes % % no % % Use of statin yes % % no % % Hypertension yes % % no % % Smoking habit yes % % no % % yes % % no % % BMI normal % % overweight % % obesity % % Catheterization report nolesion % % d mild 4 9.5% 4 7.5% moderate 3 7.1% % severe % % Presene of plaques none % % unilateral % % bilateral % % multiple % % Proedure linial % % surgial % 5 9.4% angioplasty % % Total holesterol high % % <0.001 normal % % HDL- low % % <0.001 normal % % Glyemia normal % % % % Diabetes % % LDL- high % % <0.001 normal % % TG high % % <0.001 normal % % hscrp (risk) low % % moderate % % high % % Metaboli syndrome yes % % d no 3 7.1% % Pearson s hi-square test; d Extension of Fisher s exat test. *BMI: body mass index; hscrp: high sensibility C reative protein. inativity and family story of heart disease. Most patients with severe lesions in the arteries presented altered CI-II and sdldl-. Vieira et al. 15 found similar results. Piotrowiz et al. 13 also found high perentages of obesity, high LDL- values and family history in patients with ardiovasular risk. The inrease in BMI and WC is related to CAD due to the prodution of inflammatory mediators suh as interleukin-6, adiponetin, inhibi- Journal of Cardiovasular Disease Researh, Vol 7, Issue 2, Apr-Jun,

4 Table 2: Charateristis of the patients, aording to LDL/HDL- (Castelli Index II) LDL-/HDL- Waist irunferene high % % normal % % Physial ativity praties yes % % no % % Use of statin yes % % no % % Hypertension yes % % no % % Smoking habit yes % % no % % yes % % no % % BMI normal % % overweight % % obesity % % Catheterization report nolesion % % d mild % 4 6.3% moderate 1 3.3% % severe % % Presene of plaques none % % unilateral % % bilateral % % multiple % % Proedure linial % % d surgial % % angioplasty % % Total holesterol high % % <0.001 normal % % HDL- low % % normal % % Glyemia normal % % % % Diabetes % % LDL- high % % <0.001 normal % % TG high % % normal % % hscrp (risk) low % % moderate % % high % % Metaboli syndrome yes % % >0.999 d no % % Pearson s hi-square test; d Extension of Fisher s exat test. *BMI: body mass index; hscrp: high sensibility C reative protein. tor of plasminogen ativator -1 and tumor nerosis fator α. The imbalane in the release of these hemial mediators assoiated with physial inativity hanges several fators assoiated with CAD favoring the development of a low intensity inflammatory proess that results in a loal immune response haraterized by inreased prodution of inflammatory biomarkers as hscrp and prodution of free radials that damage the vasular endothelium. Authors have shown that high Table 3: Charateristis of the patients, aording to TG/HDL- TG/HDL- Waist irunferene high % % Physial ativity praties normal % % yes % % no % % Use of statin yes % % no % % Hypertension yes % % no % % Smoking habit yes % % no % % yes % % no % % BMI normal % % overweight % % obesity % % Catheterization report nolesion % % d mild 2 3.0% % moderate % % severe % % Presene of plaques none % % unilateral % % bilateral % % multiple % 1 3.6% Proedure linial % % d surgial % 1 3.6% angioplasty % % Total holesterol high % % normal % % HDL- low % % <0.001 normal % % Glyemia normal % % % % Diabetes % % LDL- high % % normal % % TG high % 0 0.0% <0.001 normal % % hscrp (risk) low % % moderate % % high % % Metaboli syndrome yes % % d no 5 7.5% % Pearson s hi-square test; d Extension of Fisher s exat test. *BMI: body mass index; hscrp: high sensibility C reative protein. levels of hscrp, regardless of the lipid profile, inrease the risk of aute myoardial infartion. 2,16,17 This protein is produed by the liver and regulated by ytokines IL-1, IL -6 and TNF-α. It may also be produed by adipoytes and inreases 88 Journal of Cardiovasular Disease Researh, Vol 7, Issue 2, Apr-Jun, 2016

5 in response to ative infetion or aute inflammation. Moderate inreases are assoiated with hroni inflammatory onditions suh as atheroslerosis. 2,3,18-20 Our results also show that the group with altered TG/HDL- has higher perentages of subjets with higher values of TC and LDL- and dereased HDL- levels. It is also possible to observe that this group presented the higher perentages of arterial severe lesions and higher number of plaques. HDL- and TG levels and sdldl- may be onsidered independent risk fators for CAD. 4 Vieira et al. 15 and Yadav et al. 21 showed that triglyeride levels represent a preditor of sdldl-, while inreased levels of HDL- are preditive for larger LDL- partile. Mogarekar, Kulkari 22 suggest that the quality of sdldl- is more important than only LDL- levels. Manabe et al. 23 and Nishikido et al. 24 found perentages signifiantly higher of patients with CAD assoiated with sdldl. The sdldl- (diameter less than 25.5 nm) is assoiated with three times higher rate of myoardial infartion. 1 9 Even observing high perentages of individuals possessing dyslipidemia, more than 80% of the patients related lipid lowering treatment. The use of the ratios proposed by CI-I, CI-II and the estimate of LDL- partile size may represent simple parameters for estimating ardiovasular risks without worrying with the use and interpretation of logarithms that an beome unfeasible in linial pratie. They may also be effetive to evaluate the effetiveness of therapies that have been used by the dotor. Besides, they allow the minimization of the high osts that would be required by using speialized tehniques and the need of qualified team for performing the logarithms and sores proposed by numerous studies in the literature. CONCLUSION It is extremely important to have a omplete metaboli profile from patients with heart disease diagnosis in order to work on seondary prevention. Our results show that Castelli Index and the ratio TG/ HDL- are positively assoiated to modifiations in the lipid profile, BMI, WC and hscrp levels as well as the physial inativity and the presene of MS. Improvement of these risk fators may provide a better life expetane for the patients. ACKNOWLEDGEMENT We thank the patients who partiipated in this study. CONFLICT OF INTEREST All authors delare no onflit of interests and no funding supports. REFERENCES 1. The National Cholesterol Eduation Program (NCEP) Expert Panel on Detetion, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285(19): Coffman E, Rihmond-Bryant J. Multiple biomarker models for improved risk estimation of speifi ardiovasular diseases related to metaboli syndrome: a ross-setional study. Popul Health Metr. 2015;13(1):1. doi: /s Jiménez MC, Rexrode KM, Glynn RJ, Ridker PM, Gaziano JM, Sesso HD. 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Castelli Index and estimative of LDL- partile size may still help in the linial pratie?. J Cardiovas Disease Res. 2016;7(2):86-9. Journal of Cardiovasular Disease Researh, Vol 7, Issue 2, Apr-Jun,