- Email: [email protected]
Heterogeneity of Low-Density Lipoprotein Particle Number at Normal Concentrations of Lipoprotein (a) in Hyperlipidemia Patients
252
Journal of Clinical Lipidology, Vol 6, No 3, June 2012
102 The HS-Omega-3 Index Is Favorably Associated with Triglycerides and Inflammatory Markers: Data from 100,000 Patients William S. Harris, PhD, Stephen Varvel, PhD, James Borowski, MS, Jenny Ward, MS, Joe McConnell, PhD, James V. Pottala, MS, (Richmond, VA) Synopsis: The HS-Omega-3 Index (RBC eicosapentaenoic acid + docosahexaenoic acid; EPA + DHA) has been shown to be independently and inversely related to risk for sudden cardiac death and for acute coronary syndromes (ACS). This relationship could be mediated by effects of omega-3 fatty acids (O3FA) on other coronary heart disease (CHD) risk markers. Purpose: The purpose of this study was to examine the cross-sectional relationships between the HS-Omega-3 Index and selected lipid/lipoprotein fractions and inflammatory markers in a large clinical dataset. Methods: Data on the HS-Omega-3 Index and lipid (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides) and inflammatory markers (C-reactive protein [CRP] and Lipoprotein-associated phospholipase A2 [LpPLA2]) were collected from tests performed at HDL. No information other than age and sex were available for these clinical samples. Nonparametric splines with 95% confidence bands were used for exploratory analysis. Partial (adjusted for age) Pearson’s correlations were calculated cross-sectionally between the Index and the biomarkers; non-normally distributed variables were logtransformed. Results: The most significant difference between genders was that in women the omega-3 index had a direct relation with HDL-C; however, in men they were independent (Table 1 and Figure 1). The other biomarkers had similar magnitudes between genders. The inflammatory markers had the strongest (inverse) correlation with the omega-3 index and LDL-C had the weakest. Conclusions: The inverse association between the HSOmega-3 Index and coronary heart disease could be, in part, mediated by favorable relations with known risk markers.
Table 1
Age-adjusted correlations with Ln(Omega-3 Index)
Biomarker
Male
N
Female
n
Ln(TGs) HDL-C LDL-C Ln(CRP) Lp-PLA2
20.095 0.006* 20.085 20.165 20.147
52,944 52,930 52,933 47,596 52,772
20.139 0.108 20.062 20.146 20.121
55,566 55,539 55,542 49,334 55,264
TGs, triglycerides. *P 5 .18, all other P , .0001.
Figure 1 Relationship between the omega-3 index (mean [SD] of 5.2% [2.0%]) and biomarkers shown using splines with 95% confidence bands. Upper bounds of biomarkers are about their mean + 3SD.
103 Heterogeneity of Low-Density Lipoprotein Particle Number at Normal Concentrations of Lipoprotein (a) in Hyperlipidemia Patients Hector Malave, MD, Richard Wright, MD, Tara Dall, MD, Barney Beaver, DO, Ray Pourfarzib, PhD, (Atlanta, GA) Synopsis: Lipoprotein (a) [Lp(a)] is used commercially as a marker to predict cardiovascular disease. The clinical utility of routine measurement of Lp(a) is unclear. Furthermore, limited data are available that can be used to evaluate the relationship between low-density lipoprotein particle number (LDL-P) and Lp(a) concentration. Purpose: To determine the correlation between LDL-P and Lp(a) in an unselected population of patients undergoing lipid analysis. Methods: Cases comprised subjects with at least one of the following diagnoses in the database as reported by the ordering physician: hyperlipidemia, clinical coronary heart disease, diabetes mellitus, or symptomatic carotid artery disease. LDL-P levels were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Lipids and Lp(a) were measured by standardized automated methods, and LDL cholesterol was calculated by the Friedewald equation. The query for the NMR and Lp(a) were obtained from January 1, 2009, through October 31, 2011, with a sample size of 3024 subjects. Results: Among the 3024 subjects, the mean age was 60 6 16 years (51% female). The mean Lp(a) concentration was 83 mg/dL, and the mean LDL-P concentration was 1389 nmol/L. There was no correlation between Lp(a) and LDL-P levels (r2 5 0.0012). At Lp(a) levels of less than
Abstracts 30 mg/dL, 23% had LDL-P concentrations less than 1001 nmol/L, 25% were between 1001 and 1299 nmol/L, and 52% of the subjects were greater than 1300 nmol/L. At low LDL-P concentration less than 1000 nmol/L, approximately 41% of the subjects had Lp (a) concentrations less than 30 mg/dL. Conclusions: These data demonstrate that many patients with normal Lp(a) levels of less than 30 mg/dL, had discordant elevation of LDL-P concentration, with 52% of them having LDL-P levels greater than 1300 nmol/L. These results suggest that many patients with low Lp(a) concentrations could retain significant residual atherogenic risk because of their high LDL-P levels.
104 Circulating HDL/Apolipoprotein A1 des Q243 Ratio Is Significantly Correlated with Coronary Artery Disease and Diabetes Mellitus Boriana R. Nikolova, MD, Matthew R. Schaab, PhD, Chad R. Borges, PhD, David Drachman, PhD, Christian S. Breburda, MD, (Phoenix, AZ) Synopsis: Recently, oxidized high-density lipoprotein (HDL) and in particular apolipoproteins have become available for routine measurement. Yet their significance as a cardiac risk factor is not fully understood. Purpose: We hypothesize that the ratio HDL/apolipoprotein A1 (Apo A1) des Q243 is associated with risk factors of heart diseases. Methods: We studied blood samples from 100 consecutive patients who presented for cardiovascular evaluation. Clinical and diagnostic data for these patients were collected. Electrospray ionization-based mass spectrometric immunoassay was used to ascertain the relative degree of C-terminal glutamine residue truncation (des-Q243) of Apo A1. Results: We tested 100 patients with a mean age of 54 (611) years, male (n 5 59) and female (n 5 41). In these
Figure 1 Association of HDL/apoA1 des Q243 ratio with CAD and DM. CAD, coronary artery disease; DM, diabetes mellitus.
253 Table 1 and DM
Association of HDL/apoA1 des Q243 ratio with CAD
Number of patients HDL/apoA1 des Q243 p.c. HDL/apoA1 des Q243 2-tailed
CAD
DM
38 0.236 0.045
32 0.231 0.049
CAD, coronary artery disease; DM, diabetes mellitus; HDL, highdensity lipoprotein.
100 patients, 38 had been previously diagnosed with coronary artery disease, 25 had an angiographically confirmed diagnosis of myocardial infarct, and 32 patients had diabetes mellitus (DM). Our test results showed a significant positive correlation between the ratio of HDL/ apoA1 des Q243 and CAD (Pearson correlation 5 0.236, sig. [2-tailed] 5 0.045) and between the ratio of HDL/ apoA1 des Q243 and DM (Pearson Correlation 5 0.231, sig. [2-tailed] 5 0.049). Conclusions: HDL/apoA1 des Q243 ratio is significantly correlated with the presence of coronary artery disease and DM and holds promise as a new cardiac risk factor.
105 Changes in Lipoprotein-associated Phospholipase A2 with Ezetimibe/Simvastatin Co-administered with ER Niacin in Type II Hyperlipidemia Ngoc-Anh Le, PhD, Monica Farkas-Epperson, PhD, Ran Jin, MD, Andrew M. Tershakovec, MD, MPH, David R. Neff, DO, Robert Wolfert, PhD, Joanne E. Tomassini, PhD, Peter Wilson, MD, (Atlanta, GA) Synopsis: High levels of lipoprotein-associated phospholipase A2 (LpPLA2) are associated with increased risk of cardiovascular disease. LpPLA2 is an inflammatory enzyme marker and is less prone to effects of systemic infection as are other inflammatory markers such as Creactive protein (hsCRP). In a previously reported study, co-administration of ezetimibe/simvastatin (E/S) 10/20 mg with extended-release niacin up to 2 g/day (N) reduced low-density lipoprotein cholesterol and increased highdensity lipoprotein cholesterol levels significantly more than E/S and N alone in patients with type IIa/IIb hyperlipidemia (T2HLP) during 24 weeks. The combination also decreased hsCRP levels significantly more than N, and comparably with E/S. Purpose: The current study examines the effect of combination E/S+N versus N and E/S therapies on LpPLA2 concentration (PLAC) and activity (ACAM) in T2HLP patients during 24 weeks. Methods: This was an analysis of a 24-week, multicenter, randomized, double-blind study in T2HLP patients who received E/S (10/20 mg), N (2g), or combination E/S+N. N was titrated over 12 weeks to 2 g/day from an initial
Journal of Clinical Lipidology, Vol 6, No 3, June 2012
102 The HS-Omega-3 Index Is Favorably Associated with Triglycerides and Inflammatory Markers: Data from 100,000 Patients William S. Harris, PhD, Stephen Varvel, PhD, James Borowski, MS, Jenny Ward, MS, Joe McConnell, PhD, James V. Pottala, MS, (Richmond, VA) Synopsis: The HS-Omega-3 Index (RBC eicosapentaenoic acid + docosahexaenoic acid; EPA + DHA) has been shown to be independently and inversely related to risk for sudden cardiac death and for acute coronary syndromes (ACS). This relationship could be mediated by effects of omega-3 fatty acids (O3FA) on other coronary heart disease (CHD) risk markers. Purpose: The purpose of this study was to examine the cross-sectional relationships between the HS-Omega-3 Index and selected lipid/lipoprotein fractions and inflammatory markers in a large clinical dataset. Methods: Data on the HS-Omega-3 Index and lipid (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides) and inflammatory markers (C-reactive protein [CRP] and Lipoprotein-associated phospholipase A2 [LpPLA2]) were collected from tests performed at HDL. No information other than age and sex were available for these clinical samples. Nonparametric splines with 95% confidence bands were used for exploratory analysis. Partial (adjusted for age) Pearson’s correlations were calculated cross-sectionally between the Index and the biomarkers; non-normally distributed variables were logtransformed. Results: The most significant difference between genders was that in women the omega-3 index had a direct relation with HDL-C; however, in men they were independent (Table 1 and Figure 1). The other biomarkers had similar magnitudes between genders. The inflammatory markers had the strongest (inverse) correlation with the omega-3 index and LDL-C had the weakest. Conclusions: The inverse association between the HSOmega-3 Index and coronary heart disease could be, in part, mediated by favorable relations with known risk markers.
Table 1
Age-adjusted correlations with Ln(Omega-3 Index)
Biomarker
Male
N
Female
n
Ln(TGs) HDL-C LDL-C Ln(CRP) Lp-PLA2
20.095 0.006* 20.085 20.165 20.147
52,944 52,930 52,933 47,596 52,772
20.139 0.108 20.062 20.146 20.121
55,566 55,539 55,542 49,334 55,264
TGs, triglycerides. *P 5 .18, all other P , .0001.
Figure 1 Relationship between the omega-3 index (mean [SD] of 5.2% [2.0%]) and biomarkers shown using splines with 95% confidence bands. Upper bounds of biomarkers are about their mean + 3SD.
103 Heterogeneity of Low-Density Lipoprotein Particle Number at Normal Concentrations of Lipoprotein (a) in Hyperlipidemia Patients Hector Malave, MD, Richard Wright, MD, Tara Dall, MD, Barney Beaver, DO, Ray Pourfarzib, PhD, (Atlanta, GA) Synopsis: Lipoprotein (a) [Lp(a)] is used commercially as a marker to predict cardiovascular disease. The clinical utility of routine measurement of Lp(a) is unclear. Furthermore, limited data are available that can be used to evaluate the relationship between low-density lipoprotein particle number (LDL-P) and Lp(a) concentration. Purpose: To determine the correlation between LDL-P and Lp(a) in an unselected population of patients undergoing lipid analysis. Methods: Cases comprised subjects with at least one of the following diagnoses in the database as reported by the ordering physician: hyperlipidemia, clinical coronary heart disease, diabetes mellitus, or symptomatic carotid artery disease. LDL-P levels were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Lipids and Lp(a) were measured by standardized automated methods, and LDL cholesterol was calculated by the Friedewald equation. The query for the NMR and Lp(a) were obtained from January 1, 2009, through October 31, 2011, with a sample size of 3024 subjects. Results: Among the 3024 subjects, the mean age was 60 6 16 years (51% female). The mean Lp(a) concentration was 83 mg/dL, and the mean LDL-P concentration was 1389 nmol/L. There was no correlation between Lp(a) and LDL-P levels (r2 5 0.0012). At Lp(a) levels of less than
Abstracts 30 mg/dL, 23% had LDL-P concentrations less than 1001 nmol/L, 25% were between 1001 and 1299 nmol/L, and 52% of the subjects were greater than 1300 nmol/L. At low LDL-P concentration less than 1000 nmol/L, approximately 41% of the subjects had Lp (a) concentrations less than 30 mg/dL. Conclusions: These data demonstrate that many patients with normal Lp(a) levels of less than 30 mg/dL, had discordant elevation of LDL-P concentration, with 52% of them having LDL-P levels greater than 1300 nmol/L. These results suggest that many patients with low Lp(a) concentrations could retain significant residual atherogenic risk because of their high LDL-P levels.
104 Circulating HDL/Apolipoprotein A1 des Q243 Ratio Is Significantly Correlated with Coronary Artery Disease and Diabetes Mellitus Boriana R. Nikolova, MD, Matthew R. Schaab, PhD, Chad R. Borges, PhD, David Drachman, PhD, Christian S. Breburda, MD, (Phoenix, AZ) Synopsis: Recently, oxidized high-density lipoprotein (HDL) and in particular apolipoproteins have become available for routine measurement. Yet their significance as a cardiac risk factor is not fully understood. Purpose: We hypothesize that the ratio HDL/apolipoprotein A1 (Apo A1) des Q243 is associated with risk factors of heart diseases. Methods: We studied blood samples from 100 consecutive patients who presented for cardiovascular evaluation. Clinical and diagnostic data for these patients were collected. Electrospray ionization-based mass spectrometric immunoassay was used to ascertain the relative degree of C-terminal glutamine residue truncation (des-Q243) of Apo A1. Results: We tested 100 patients with a mean age of 54 (611) years, male (n 5 59) and female (n 5 41). In these
Figure 1 Association of HDL/apoA1 des Q243 ratio with CAD and DM. CAD, coronary artery disease; DM, diabetes mellitus.
253 Table 1 and DM
Association of HDL/apoA1 des Q243 ratio with CAD
Number of patients HDL/apoA1 des Q243 p.c. HDL/apoA1 des Q243 2-tailed
CAD
DM
38 0.236 0.045
32 0.231 0.049
CAD, coronary artery disease; DM, diabetes mellitus; HDL, highdensity lipoprotein.
100 patients, 38 had been previously diagnosed with coronary artery disease, 25 had an angiographically confirmed diagnosis of myocardial infarct, and 32 patients had diabetes mellitus (DM). Our test results showed a significant positive correlation between the ratio of HDL/ apoA1 des Q243 and CAD (Pearson correlation 5 0.236, sig. [2-tailed] 5 0.045) and between the ratio of HDL/ apoA1 des Q243 and DM (Pearson Correlation 5 0.231, sig. [2-tailed] 5 0.049). Conclusions: HDL/apoA1 des Q243 ratio is significantly correlated with the presence of coronary artery disease and DM and holds promise as a new cardiac risk factor.
105 Changes in Lipoprotein-associated Phospholipase A2 with Ezetimibe/Simvastatin Co-administered with ER Niacin in Type II Hyperlipidemia Ngoc-Anh Le, PhD, Monica Farkas-Epperson, PhD, Ran Jin, MD, Andrew M. Tershakovec, MD, MPH, David R. Neff, DO, Robert Wolfert, PhD, Joanne E. Tomassini, PhD, Peter Wilson, MD, (Atlanta, GA) Synopsis: High levels of lipoprotein-associated phospholipase A2 (LpPLA2) are associated with increased risk of cardiovascular disease. LpPLA2 is an inflammatory enzyme marker and is less prone to effects of systemic infection as are other inflammatory markers such as Creactive protein (hsCRP). In a previously reported study, co-administration of ezetimibe/simvastatin (E/S) 10/20 mg with extended-release niacin up to 2 g/day (N) reduced low-density lipoprotein cholesterol and increased highdensity lipoprotein cholesterol levels significantly more than E/S and N alone in patients with type IIa/IIb hyperlipidemia (T2HLP) during 24 weeks. The combination also decreased hsCRP levels significantly more than N, and comparably with E/S. Purpose: The current study examines the effect of combination E/S+N versus N and E/S therapies on LpPLA2 concentration (PLAC) and activity (ACAM) in T2HLP patients during 24 weeks. Methods: This was an analysis of a 24-week, multicenter, randomized, double-blind study in T2HLP patients who received E/S (10/20 mg), N (2g), or combination E/S+N. N was titrated over 12 weeks to 2 g/day from an initial