Association of Paraoxonase-1 Q192R (rs662) Single Nucleotide Variation with Cardiovascular Risk in Coffee Harvesters of Central Colombia

Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, hydrolyzes several organophosphate pesticides and oxidized lipids. The PON1 Q192R polymorphism affects the catalytic efficiency and is considered a risk factor for pesticide intoxication and cardiovascular disease (CVD) but the association is not consistent between individuals or populations. We aimed to study the association of PON1 Q192R polymorphism with CVD risk in coffee harvesters of central Colombia. Demographics were collected from 205 subjects via standardized questionnaires. Lipid profiles and serum butyrylcholinesterase (BChE) were measured by standard procedures. The calculated 10-year atherosclerotic CVD (ASCVD) risk was used as the cardiovascular risk estimate. Q192R genotype was determined by real-time PCR. Prevalence of hypertension, hypercholesterolemia, and the 10-year ASCVD risk was 33%, 62%, and 22%, respectively. BChE levels were no indicative of recent pesticide exposure, although a positive correlation was observed with BChE and hypercholesterolemia. The Q192R genotype frequencies were 38% (QQ), 44% (QR), and 18% (RR). We found an association of the 192Q genotype with hypertension. The results of this study signal the importance to evaluate the influence and potential interactions of BChE and PON1 192Q allele with known genetic and environmental factors implicated in the pathogenesis of CVD.

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Genetic polymorphisms of paraoxonase 1 and susceptibility to atherogenesis

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh1310629g ◽

2013 ◽

Vol 141 (9-10) ◽

pp. 629-633 ◽

Cited By ~ 8

Author(s):

Ivana Grubisa ◽

Petar Otasevic ◽

Nada Dimkovic ◽

Ivana Nedeljkovic ◽

Bosko Toljic ◽

...

Keyword(s):

Oxidative Stress ◽

Clinical Manifestations ◽

Density Lipoprotein ◽

Rflp Analysis ◽

Catalytic Efficiency ◽

Paraoxonase 1 ◽

Gene Variants ◽

Pon1 Gene ◽

Genotype Frequencies ◽

Significant Difference

Introduction. Paraoxonase 1 (PON1) is a multifunctional enzyme associated with high-density lipoprotein particles (HDL). It is a cellular antioxidant that hydrolyses oxidized macromolecules, especially low-density lipoproteins (ox-LDL). Because increased oxidative stress is believed to play a crucial role in the initiation and propagation of atherosclerosis, coding (Q192R and L55M) and promoter (C(-107)T) region polymorphisms of pon1 gene, that are responsible for catalytic efficiency, activity and the level of the enzyme, have been of great interest as a potential markers of susceptibility for atherogenesis. Objective. The aim of the study was to assess possible association between these pon1 gene variants and clinical manifestations of the atherosclerosis and oxidative stress. Methods. A total of 60 angiographically documented patients with manifested atherosclerotic disease and 100 control individuals were analyzed. Genomic DNA was isolated from the peripheral blood cells and genotyping was performed using polymerase chain reaction followed by the restriction fragment length polymorphism (PCR-RFLP) analysis. Results No significant difference in allele and genotype frequencies of all three examined polymorphisms was found between the atherosclerotic patients and healthy controls. The obtained results could not support an association of pon1 gene variants with the oxidative stress and atherogenesis. Conclusion. These polymorphisms cannot be considered risk factors of atherosclerosis in Serbian population. A larger study is required in order to establish possible contribution of pon1 variants to atherosclerosis-related cardiovascular diseases.

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Acute Stress-Induced Blood Lipid Reactivity in Hypertensive and Normotensive Men and Prospective Associations with Future Cardiovascular Risk

Journal of Clinical Medicine ◽

10.3390/jcm10153400 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3400

Author(s):

Cathy Degroote ◽

Roland von Känel ◽

Livia Thomas ◽

Claudia Zuccarella-Hackl ◽

Jens C. Pruessner ◽

...

Keyword(s):

Essential Hypertension ◽

Cardiovascular Risk ◽

Stress Reactivity ◽

Density Lipoprotein ◽

Blood Lipid ◽

Lipoprotein Cholesterol ◽

Cvd Risk ◽

P Values ◽

D Dimer

Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension.

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Cardiovascular risk in obese patients with chronic periodontitis: a clinical controlled study

Revista de Odontologia da UNESP ◽

10.1590/s1807-25772013000300008 ◽

2013 ◽

Vol 42 (3) ◽

pp. 188-195 ◽

Cited By ~ 2

Author(s):

Juliana Rico Pires ◽

Thaís Uenoyama Dezem ◽

Eliane Marçon Barroso ◽

Benedicto Egbert Corrêa de Toledo ◽

Sally Cristina Moutinho Monteiro ◽

...

Keyword(s):

Cardiovascular Risk ◽

Periodontal Disease ◽

Total Cholesterol ◽

Chronic Periodontitis ◽

Cardiovascular Events ◽

Density Lipoprotein ◽

Controlled Study ◽

Moderate Increase ◽

Obese Patients ◽

Cvd Risk

INTRODUCTION: Studies have shown that obesity is considered a risk factor for the development of periodontal disease and cardiovascular events. OBJECTIVE: The objective was to evaluate the risk for cardiovascular diseases (CVDs) in obese patients with and without periodontal. MATERIAL AND METHOD: One hundred patients were divided into four groups: Group O - obese without chronic periodontitis (n=25); Group OP - obese with chronic periodontitis (n=25); Group NO - non-obese without chronic periodontitis (n=25); and Group NOP - non-obese with chronic periodontitis (n=25). Demographic and laboratorial data (total cholesterol, high-density lipoprotein - HDL and low-density lipoprotein - LDL, triglycerides, and glucose); anthropometric measurements (body mass index - BMI; waist circumference - WC; body fat - BF); blood pressure; and periodontal parameters (bleeding on probing - BOP, periodontal probing depth - PPD, and the clinical attachment level - CAL) were evaluated. Cardiovascular risk was obtained according to the PROCAM's score. The correlation between obesity, periodontal disease and risk for CVD was verified by Spearman's test (α = 0.05). RESULT: The group OP showed a statistically higher rate of PPD > 7 mm (11.2 ± 2.03) when compared with other groups, as well as higher levels of triglycerides, total cholesterol, and LDL (p<0.05). The risk for CVD was statistically higher in the group OP (28.1 ± 3.3) when compared with group O (16.5 ± 3.5), group NOP (12.8 ± 3.9), and group NO (7.7 ± 0.9). Obesity and periodontal disease are directly related to a moderate increase in CVD risk (r = 0.53, p <0.0001 and r = 0.62, p <0.0001, respectively). CONCLUSION: It was concluded that obesity and periodontal disease increases the risk to cardiovascular events.

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404Impact of cardiovascular risk factors for the development of cardiovascular disease: Results from MORGAM and BiomarCaRE consortia

European Heart Journal ◽

10.1093/eurheartj/ehz747.0100 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

C Magnussen

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Cardiovascular Risk ◽

Substantial Reduction ◽

Density Lipoprotein ◽

Daily Smoking ◽

Cvd Risk ◽

Coronary Death ◽

Cardiac Revascularization ◽

The Impact

Abstract Background Knowledge about the impact of modifiable risk factors for cardiovascular disease (CVD) onset is essential to improve CVD prevention. Purpose We estimated population-attributable fractions (PAFs) of body-mass-index (BMI), systolic blood pressure (SBP), diabetes, blood lipids (non-high-density lipoprotein cholesterol; non-HDL-C) and daily smoking for CVD. Methods Harmonized data from MOnica Risk, Genetics, Archiving and Monograph (MORGAM) and Biomarkers for Cardiovascular Risk Assessment in Europe (BiomaCaRE) consortia were used to calculate hazard ratios (HRs; 95% CI) and PAFs for incident CVD (myocardial infarction or coronary death, unstable angina, cardiac revascularization, ischemic stroke). PAFs for single risk factors or any combination of them were estimated using methods by Laaksonen 2011. Results We included 150,190 participants (77,801 men and 72,389 women) without CVD at baseline. Strongest associations were seen for SBP ≥160 mmHg (HR 1.79, 1.67–1.92 men; HR 1.93, 1.75–2.14 women), diabetes (HR 2.02, 1.86–2.20 men; HR 2.29, 2.06–2.55 women), non-HDL-C ≥220 mg/dL (HR 3.11, 2.49–3.88 men; HR 2.27, 1.68–3.05 women), daily smoking (HR 1.82, 1.73–1,90 men; HR 2.16, 2.0–2.33 women). Table 1 provides PAFs for incident CVD. Overall PAFs for men and women were 73.7% (67.7–79.1) and 73.3% (64.9–80.9). Table 1. PAFs (%) for 5-year incident CVD Risk factor/category PAFs (95% CI), men PAFs (95% CI), women Underweight 0.1 (−0.1, 0.3) 0.2 (−0.1, 0.6) Pre-obesity 6.6 (4.3, 8.9) 4.3 (1.5, 6.9) Obesity 3.9 (2.7, 5.3) 8.0 (5.3, 10.5) SBP 130 to <140 mmHg 2.8 (1.7, 4.0) 2.7 (1.3, 4.0) SBP 140 to <160 mmHg 9.7 (8.1, 11.3) 9.3 (6.7, 11.6) SBP ≥160 mmHg 11.3 (9.7, 12.8) 18.9 (16.2, 21.8) Diabetes 5.2 (4.5, 6.2) 7.8 (6.5, 9.4) non-HDL-C 100 to <145 mg/dL 4.3 (1.8, 6.4) 3.3 (0.5, 6.5) non-HDL-C 145 to <185 mg/dL 13.9 (9.8, 17.5) 11.3 (6.0, 16.2) non-HDL-C 185 to <220 mg/dL 15.8 (12.8, 18.4) 12.8 (8.8, 17.0) non-HDL-C ≥220 mg/dL 16.7 (14.6, 18.5) 17.0 (12.5, 21.1) Daily smoking 16.5 (15.0, 18.3) 12.3 (10.7, 13.7) The N CVD events/N used was 8,302/77,801 for men and 4,071/72,389 for women. Conclusion Uncontrolled risk factors, especially non-HDL-C and SBP in the highest category, daily smoking and diabetes had the highest impact for incident CVD. All risk factors combined accounted for a PAF of 73%. Targeting risk factors would lead to a substantial reduction of CVD onset. Acknowledgement/Funding BiomarCaRE: EU Seventh Framework Programme (FP7/2007-2013), No. HEALTH-F2-2011-278913. MORGAM: EU FP 7 CHANCES (HEALTH-F3-2010-242244).

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Markers of Increased Cardiovascular Risk in Postmenopausal Women: Focus on Oxidized-LDL and HDL Subpopulations

Disease Markers ◽

10.1155/2013/724706 ◽

2013 ◽

Vol 35 ◽

pp. 85-96 ◽

Cited By ~ 21

Author(s):

Filipa Mascarenhas-Melo ◽

José Sereno ◽

Edite Teixeira-Lemos ◽

Sandra Ribeiro ◽

Petronila Rocha-Pereira ◽

...

Keyword(s):

Uric Acid ◽

Cardiovascular Risk ◽

Postmenopausal Women ◽

Oxidized Ldl ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Population Based ◽

Paraoxonase 1 ◽

Healthy Population ◽

Necrosis Factor Alpha

Objective. To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers.Methods. 56 men and 68 women (48 pre- and 20 postmenopause) were enrolled in the study. The following markers were analyzed: blood pressure (BP), body mass index (BMI), waist circumference (WC), glucose, total cholesterol (total-c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), oxidized-LDL (Ox-LDL), HDL-c and subpopulations, paraoxonase-1 activity, hsCRP, uric acid, tumor necrosis factor alpha (TNF-α), adiponectin, vascular endothelial growth factor (VEGF), and intercellular adhesion molecular 1 (ICAM1).Results.Relative to the women, men present significantly increased BMI, WC, BP, glucose, total-c, TGs, LDL-c, Ox-LDL, uric acid, and TNF-αand reduced adiponectin and total and large HDL-c. The protective profile of women is lost after menopause with a significantly increased BMI, WC, BP, glucose, LDL-c, Ox-LDL, hsCRP, and VEGF and decreased total and large HDL-c. Significant correlations were found in women population and in postmenopausal women between Ox-LDL and total, large, and small HDL-c and between TNF-αand total, large, and small HDL-c, LDL-c, and Ox-LDL.Conclusions. Men present higher CVR than women who lost protection after menopause, evidenced by nontraditional markers, including Ox-LDL and HDL subpopulations.

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Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1

Clinical Science ◽

10.1042/cs20040187 ◽

2004 ◽

Vol 107 (5) ◽

pp. 435-447 ◽

Cited By ~ 176

Author(s):

Sara P. DEAKIN ◽

Richard W. JAMES

Keyword(s):

Environmental Factors ◽

Serum Concentration ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Serum Levels ◽

Paraoxonase 1 ◽

Pon1 Activity ◽

Human Populations ◽

Genetic And Environmental Factors ◽

Oxidatively Modified

PON1 (paraoxonase-1) is an HDL (high-density lipoprotein)-associated enzyme capable of hydrolysing diverse substrates from OP (organophosphate) toxins to oxidized phospholipids. As such, it has been linked with both the prevention of OP poisoning and inhibition of atherosclerosis initiated by oxidatively modified LDL (low-density lipoprotein). Mice deficient in PON1 are more susceptible to OP poisoning and oxidative stress and more prone to develop atherosclerosis than their wild-type siblings. There are a number of polymorphisms in the PON1 gene which affect serum PON1 activity and concentration. Many (but not all) studies in human populations have suggested that these polymorphisms may be a risk factor for atherosclerosis. The serum concentration of PON1 across the general population is highly variable and there is some debate as to whether genotype or phenotype (i.e. the quantity or quality of the enzyme) is most accurately associated with risk of disease development. What is clear is that factors influencing serum levels of PON1, be they genetic or environmental, will, in turn, affect the capacity of HDL to protect LDL from oxidation and, consequently, may be linked to atherosclerosis. This review will focus on mechanisms which determine the serum concentration of PON1, including gene expression and genetic polymorphisms, protein secretion and association with HDL, pharmacological and environmental factors.

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Fasting and non-fasting lipid profile for cardiovascular risk assessments using China ASCVD risk estimator and Europe SCORE risk charts in Chinese participants

10.21203/rs.3.rs-60051/v1 ◽

2020 ◽

Author(s):

Shi-Lan Zhang ◽

Xiao Du ◽

Jin Xu ◽

Qun-yan Xiang ◽

Ling Liu

Keyword(s):

Cardiovascular Risk ◽

Blood Lipids ◽

Risk Estimation ◽

Kappa Statistic ◽

Serum Levels ◽

Cvd Risk ◽

Risk Charts ◽

Ascvd Risk ◽

Risk Estimator ◽

Score Risk

Abstract Background Previous studies have shown that non-fasting lipids have similar values in cardiovascular risk estimation as fasting, but it is not clear whether this could also be applicable to Chinese participants.Methods A total of 127 (76 men, 51 women) participants without atherosclerotic cardiovascular diseases (ASCVD) were enrolled in the study. Serum levels of blood lipids were monitored at 0 h, 2 h and 4 h after a daily breakfast. Ten-year cardiovascular disease (CVD) risk was estimated with China ASCVD risk estimator and Europe SCORE risk charts. Kappa statistic was used to determine agreement among estimators.Results there was substantial agreement between China ASCVD risk estimator based on fasting and non-fasting lipid profiles (Kappa = 0.731 or 0.718, P < 0.001), but poorly agreement between China ASCVD risk estimator and SCORE low- or high-risk chart (Kappa = 0.339 or 0.300, P < 0.001).Conclusions Promoting use of non-fasting blood lipids in diagnosis, evaluation, and prediction of CVD are feasible. Furthermore, non-fasting blood lipids could be used in China ASCVD risk estimator to evaluate assess 10-year risk of ASCVD among Chinese general participants.

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Nutrition Intervention for Reduction of Cardiovascular Risk in African Americans Using the 2019 American College of Cardiology/American Heart Association Primary Prevention Guidelines

Nutrients ◽

10.3390/nu13103422 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3422

Author(s):

Kim Allan Williams ◽

Ibtihaj Fughhi ◽

Setri Fugar ◽

Monica Mazur ◽

Sharon Gates ◽

...

Keyword(s):

Cardiovascular Risk ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Heart Association ◽

Nutrition Intervention ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Ascvd Risk ◽

Hs Crp

Introduction: The 2019 American College of Cardiology/American Heart Association (ACC/AHA) Prevention Guidelines emphasize reduction in dietary sodium, cholesterol, refined carbohydrates, saturated fat and sweetened beverages. We hypothesized that implementing this dietary pattern could reduce cardiovascular risk in a cohort of volunteers in an urban African American (AA) community church, during a 5-week ACC/AHA-styled nutrition intervention, assessed by measuring risk markers and adherence, called HEART-LENS (Helping Everyone Assess Risk Today Lenten Nutrition Study). Methods: The study population consisted of 53 volunteers who committed to eat only home-delivered non-dairy vegetarian meals (average daily calories 1155, sodium 1285 mg, cholesterol 0 mg; 58% carbohydrate, 17% protein, 25% fat). Body mass index (BMI) and fasting serum markers of cardiometabolic and risk factors were measured, with collection of any dietary deviation. Results: Of 53 volunteers, 44 (mean age 60.2 years, 37 women) completed the trial (88%); 1 was intolerant of the meals, 1 completed both blood draws but did not eat delivered food, and 7 did not return for the tests. Adherence to the diet was reported at 93% in the remaining 44. Cardiometabolic risk factors improved significantly, highlighted by a marked reduction in serum insulin (−43%, p = 0.000), hemoglobin A1c (6.2% to 6.0%, p = 0.000), weight and BMI (−10.2 lbs, 33 to 31 kg/m2, p = 0.000), but with small reductions of fasting glucose (−6%, p = 0.405) and triglyceride levels (−4%, p = 0.408). Additionally, improved were trimethylamine-N-oxide (5.1 to 2.9 µmol/L, −43%, p = 0.001), small dense low-density lipoprotein cholesterol (LDL) (24.2 to 19.1 mg/dL, −21%, p = 0.000), LDL (121 to 104 mg/dL, −14%, p = 0.000), total cholesterol (TC) (190 to 168 mg/dL, −12%, p = 0.000), and lipoprotein (a) (LP(a)) (56 to 51 mg/dL, −11%, p = 0.000); high sensitivity C-reactive protein (hs-CRP) was widely variable but reduced by 16% (2.5 to 2.1 ng/mL, p = NS) in 40 subjects without inflammatory conditions. Soluble urokinase plasminogen activator (suPAR) levels were not significantly changed. The ACC/AHA pooled cohort atherosclerotic cardiovascular disease (ASCVD) risk scores were calculated for 41 and 36 volunteers, respectively, as the ASCVD risk could not be calculated for 3 subjects with low lipid fractions at baseline and 8 subjects after intervention (p = 0.184). In the remaining subjects, the mean 10-year risk was reduced from 10.8 to 8.7%, a 19.4% decrease (p = 0.006), primarily due to a 14% decrease in low-density lipoprotein cholesterol and a 10 mm Hg (6%) reduction in systolic blood pressure. Conclusions: In this prospective 5-week non-dairy vegetarian nutrition intervention with good adherence consistent with the 2019 ACC/AHA Guidelines in an at-risk AA population, markers of cardiovascular risk, cardiometabolism, and body weight were significantly reduced, including obesity, low-density lipoprotein cholesterol (LDLc) density, LP(a), inflammation, and ingestion of substrates mediating production of trimethylamine-N-oxide (TMAO). Albeit reduced, hs-CRP and suPAR, were not lowered consistently. This induced a significant decrease in the 10-year ASCVD risk in this AA cohort. If widely adopted, this could dramatically reduce and possibly eradicate, the racial disparity in ASCVD events and mortality, if 19% of the 21% increase is eliminated by this lifestyle change.

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New Markers of Early Cardiovascular Risk in Multiple Sclerosis Patients: Oxidized-LDL Correlates with Clinical Staging

Disease Markers ◽

10.1155/2013/567162 ◽

2013 ◽

Vol 34 (5) ◽

pp. 341-348 ◽

Cited By ~ 34

Author(s):

Filipe Palavra ◽

Daniela Marado ◽

Filipa Mascarenhas-Melo ◽

José Sereno ◽

Edite Teixeira-Lemos ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cardiovascular Risk ◽

Oxidized Ldl ◽

Density Lipoprotein ◽

Paraoxonase 1 ◽

Clinical Staging ◽

Clinical Activity ◽

Serum Triglycerides ◽

Cross Sectional ◽

Multiple Sclerosis Patients

OBJECTIVES: This study aimed to characterize a population of multiple sclerosis (MS) patients in terms of traditional and new cardiovascular risk factors and assess their putative correlation with clinical disease activity (evaluated by the Expanded Disability Status Scale [EDSS]).METHODS: Thirty relapsing MS patients and 66 subjects, matched by age and sex, were enrolled in this cross-sectional study. For each subject, anthropometric data were collected and classical biochemical (including lipid profile, glucose and C reactive protein [CRP] levels) and novel markers (paraoxonase 1 [PON1] enzyme activity and contents of high-density lipoprotein [HDL] cholesterol, oxidized low-density lipoprotein [Ox-LDL], tumor necrosis factor [TNF]-alfa, vascular endothelial growth factor [VEGF] and adiponectin) were studied.RESULTS: In patients group, 23 women and 7 men were included, aged 35.00 (28.25–40.25) years and scoring a median of 2.00 (1.50–3.13) in EDSS. Comparing with controls, the most relevant differences encountered were: increased serum triglycerides (P< 0.001), Ox-LDL (P< 0.001) as well as Ox-LDL/LDL ratio and reduced small HDL (P= 0.040), accompanied by a trend to increased VEGF concentration. LDL content, especially Ox-LDL, showed positive and significant correlation with EDSS (r= 0.458;P= 0.011) and VEGF (r= 0.453;P= 0.014).CONCLUSIONS: MS patients presented a profile of early CV risk, being Ox-LDL contents a putative good marker and having correlation with the clinical activity of the disease.

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Abstract 97: Association of the Serum Myeloperoxidase/High-Density Lipoprotein Particle Ratio and Incident Cardiovascular Events in a Multi-Ethnic Population: Observations From the Dallas Heart Study

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.97 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Htet W Khine ◽

John F Teiber ◽

Robert W Haley ◽

Amit Khera ◽

Anand Rohatgi

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

Particle Concentration ◽

Coronary Revascularization ◽

Density Lipoprotein ◽

Cox Proportional Hazards ◽

High Density ◽

Paraoxonase 1 ◽

Cvd Risk ◽

Increased Risk

Introduction: Myeloperoxidase (MPO) promotes oxidation of lipoproteins whereas high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO can induce dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We hypothesized that increased serum levels of MPO indexed to HDL particle concentration would be associated with an adverse phenotype with increased CVD risk and tested this hypothesis in a large multiethnic population free of CVD at baseline. Methods: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD (57% women, 49% black). The associations of the MPO/HDLp ratio with incident ASCVD (first nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors (age, sex, race, hypertension, smoking, total cholesterol, and statin use). The median follow-up period was 9.4 years. Results: MPO/HDLp was associated directly with total cholesterol, C-reactive protein, interleukin 18, and body mass index, and inversely with PON1 arylesterase activity, HDL-C, and HDL size. In adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total CVD (aHR, 1.91, 95% CI 1.27-2.85). Conclusion: Increasing MPO indexed to HDL particle concentration at baseline is associated with increased risk of incident CVD events in a population initially free of CVD, reflecting increased inflammation and decreased PON1 arylesterase activity. This is the first report of the MPO/HDLp ratio in a large human cohort. Further studies are warranted investigating MPO/HDLp as a biomarker of HDL metabolism and CVD risk.

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