The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study
The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these as...
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MDPI AG
2021-03-01
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| Online Access: | https://www.mdpi.com/2227-9059/9/3/286 |
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| author | Gualtiero I. Colombo Vanessa Bianconi Alice Bonomi Sara Simonelli Mauro Amato Beatrice Frigerio Alessio Ravani Cecilia Vitali Daniela Sansaro Daniela Coggi Massimo R. Mannarino Kai P. Savonen Sudhir Kurl Bruna Gigante Andries J. Smit Philippe Giral Elena Tremoli Laura Calabresi Fabrizio Veglia Matteo Pirro Damiano Baldassarre on behalf of the IMPROVE Study Group |
| author_facet | Gualtiero I. Colombo Vanessa Bianconi Alice Bonomi Sara Simonelli Mauro Amato Beatrice Frigerio Alessio Ravani Cecilia Vitali Daniela Sansaro Daniela Coggi Massimo R. Mannarino Kai P. Savonen Sudhir Kurl Bruna Gigante Andries J. Smit Philippe Giral Elena Tremoli Laura Calabresi Fabrizio Veglia Matteo Pirro Damiano Baldassarre on behalf of the IMPROVE Study Group |
| author_sort | Gualtiero I. Colombo |
| collection | DOAJ |
| description | The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMT<sub>max</sub>; cIMT<sub>mean–max</sub> of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMT<sub>mean</sub>) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, <i>p</i> < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMT<sub>max</sub> and cIMT<sub>mean–max</sub>, but not with PF CC-IMT<sub>mean</sub>, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMT<sub>max</sub> or cIMT<sub>mean–max</sub> were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMT<sub>max</sub> and cIMT<sub>mean–max</sub> when the CETP concentration was below the median (HDL-C × CETP interaction, <i>p </i>= 0.001 and <i>p </i>= 0.003 for cIMT<sub>max</sub> and cIMT<sub>mean–max</sub>, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMT<sub>max</sub>. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMT<sub>max</sub>. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMT<sub>max</sub>. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent. |
| first_indexed | 2024-03-10T13:20:31Z |
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| language | English |
| last_indexed | 2024-03-10T13:20:31Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-a4f3cdccf3ab4a1aa625d0f6d2216bab2023-11-21T10:04:09ZengMDPI AGBiomedicines2227-90592021-03-019328610.3390/biomedicines9030286The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE StudyGualtiero I. Colombo0Vanessa Bianconi1Alice Bonomi2Sara Simonelli3Mauro Amato4Beatrice Frigerio5Alessio Ravani6Cecilia Vitali7Daniela Sansaro8Daniela Coggi9Massimo R. Mannarino10Kai P. Savonen11Sudhir Kurl12Bruna Gigante13Andries J. Smit14Philippe Giral15Elena Tremoli16Laura Calabresi17Fabrizio Veglia18Matteo Pirro19Damiano Baldassarre20on behalf of the IMPROVE Study GroupCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Medicine, University of Perugia, 06129 Perugia, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyDepartment of Medicine, University of Perugia, 06129 Perugia, ItalyFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, 70100 Kuopio, FinlandInstitute of Public Health and Clinical Nutrition, University of Eastern Finland, 70210 Kuopio, FinlandDepartment of Medicine, Karolinska Institutet, 17177 Stockholm, SwedenDepartment of Medicine, University Medical Center Groningen, 9700 RB Groningen, The NetherlandsDepartment of Endocrinology, Metabolism, and Prevention of Cardiovascular Diseases, Hôpital Pitié-Salpêtrière—Sorbonne University, 75651 Paris, FranceCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyDepartment of Medicine, University of Perugia, 06129 Perugia, ItalyCentro Cardiologico Monzino IRCCS, 20138 Milan, ItalyThe impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMT<sub>max</sub>; cIMT<sub>mean–max</sub> of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMT<sub>mean</sub>) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, <i>p</i> < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMT<sub>max</sub> and cIMT<sub>mean–max</sub>, but not with PF CC-IMT<sub>mean</sub>, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMT<sub>max</sub> or cIMT<sub>mean–max</sub> were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMT<sub>max</sub> and cIMT<sub>mean–max</sub> when the CETP concentration was below the median (HDL-C × CETP interaction, <i>p </i>= 0.001 and <i>p </i>= 0.003 for cIMT<sub>max</sub> and cIMT<sub>mean–max</sub>, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMT<sub>max</sub>. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMT<sub>max</sub>. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMT<sub>max</sub>. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.https://www.mdpi.com/2227-9059/9/3/286cholesteryl ester transfer proteinHDL-Catherosclerosissingle-nucleotide polymorphismscarotid intima-media thickness |
| spellingShingle | Gualtiero I. Colombo Vanessa Bianconi Alice Bonomi Sara Simonelli Mauro Amato Beatrice Frigerio Alessio Ravani Cecilia Vitali Daniela Sansaro Daniela Coggi Massimo R. Mannarino Kai P. Savonen Sudhir Kurl Bruna Gigante Andries J. Smit Philippe Giral Elena Tremoli Laura Calabresi Fabrizio Veglia Matteo Pirro Damiano Baldassarre on behalf of the IMPROVE Study Group The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study Biomedicines cholesteryl ester transfer protein HDL-C atherosclerosis single-nucleotide polymorphisms carotid intima-media thickness |
| title | The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study |
| title_full | The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study |
| title_fullStr | The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study |
| title_full_unstemmed | The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study |
| title_short | The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study |
| title_sort | association between hdl c and subclinical atherosclerosis depends on cetp plasma concentration insights from the improve study |
| topic | cholesteryl ester transfer protein HDL-C atherosclerosis single-nucleotide polymorphisms carotid intima-media thickness |
| url | https://www.mdpi.com/2227-9059/9/3/286 |
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