{"id":{"repo_id":"lund","oai_identifier":"oai:lup.lub.lu.se:4460e18c-5cda-49bc-9906-781fc3156d03"},"canonical_url":"https://search.dev.ndltd.org/etd/lund/oai:lup.lub.lu.se:4460e18c-5cda-49bc-9906-781fc3156d03","repository":{"repo_id":"lund","name":"University of Lund","base_url":"https://lup.lub.lu.se/oai"},"display":{"title":"Cardiovascular Risk Genes in Prevention and Treatment Response","abstract":"GENERAL AIM: To investigate how common single-nucleotide-polymorphisms (SNPs) that associate with cardiovascular disease (CVD) could be used in prevention and treatment of CVD. SUBJECTS: Subjects from the population-based Malmö-Diet-and-Cancer-(MDC)-Study (n=30447) and hypertensives from the Nordic-Diltiazem-(NORDIL)-Study (n=10881). METHODS AND RESULTS: A nine-SNP-lipid-genetic-risk-score was related to fluvastatin treatment-response in 395 MDC subjects with asymptomatic carotid atherosclerosis. In women, a higher score (conferring unfavorable baseline-lipid-levels) correlated with HDL-increase (P=0.001), explaining 11.6-12.9% of the variance in HDL-change. A 13-SNP-myocardial-infarction-(MI)-genetic-risk-score was related to carotid atherosclerosis-markers in 4022 MDC-subjects. The MI-gene-score associated with carotid-bulb-intima-media-thickness (IMT) (beta=0.038 standard deviations of IMT per MI-gene-score-quintile; P-trend=0.005) and plaque (odds-ratio per MI-gene-score-quintile=1.11; 95% confidence interval (CI):1.04-1.18; P=0.001) in multivariable models. It was tested if eight blood-pressure-associated SNPs affected antihypertensive treatment-response in 3863 Swedish hypertensives from NORDIL. No robust associations were identified. Finally, interactions between life-style-factors and the CVD-SNP rs4977574 on chromosome 9p21 were evaluated in 24944 MDC-subjects during 15 years follow-up. There were interactions between rs4977574 and smoking on incident CAD (P=0.035) and CVD-mortality (P=0.012). The risk conferred by rs4977574 in never-smokers (n=9642; Hazard-ratio(HR) per risk-allele(CAD)=1.26; 95%CI:1.13-1.40; HR per risk-allele(CVD-mortality)=1.40; 95%CI:1.20-1.63) was attenuated in smokers (n=7000; HR per risk-allele(CAD)=1.05; 95%CI:0.95-1.16; HR per risk-allele(CVD-mortality)=1.08; 95%CI:0.94-1.23). CONCLUSIONS: CVD-genetics identifies subjects with markers of subclinical atherosclerosis, suggesting that early atherosclerosis-prevention may be targeted to such individuals. Smoking attenuates the relative influence of the thus far strongest identified polygenic CVD-risk-locus, implying potential utility of common CVD-genetics in mainly conventional lower-risk subjects. Lipid-polymorphisms may predict statin-induced HDL-increase in women, but eight blood-pressure-SNPs did not affect antihypertensive treatment-response.","abstract_html":"GENERAL AIM: To investigate how common single-nucleotide-polymorphisms (SNPs) that associate with cardiovascular disease (CVD) could be used in prevention and treatment of CVD. SUBJECTS: Subjects from the population-based Malmö-Diet-and-Cancer-(MDC)-Study (n=30447) and hypertensives from the Nordic-Diltiazem-(NORDIL)-Study (n=10881). METHODS AND RESULTS: A nine-SNP-lipid-genetic-risk-score was related to fluvastatin treatment-response in 395 MDC subjects with asymptomatic carotid atherosclerosis. In women, a higher score (conferring unfavorable baseline-lipid-levels) correlated with HDL-increase (P=0.001), explaining 11.6-12.9% of the variance in HDL-change. A 13-SNP-myocardial-infarction-(MI)-genetic-risk-score was related to carotid atherosclerosis-markers in 4022 MDC-subjects. The MI-gene-score associated with carotid-bulb-intima-media-thickness (IMT) (beta=0.038 standard deviations of IMT per MI-gene-score-quintile; P-trend=0.005) and plaque (odds-ratio per MI-gene-score-quintile=1.11; 95% confidence interval (CI):1.04-1.18; P=0.001) in multivariable models. It was tested if eight blood-pressure-associated SNPs affected antihypertensive treatment-response in 3863 Swedish hypertensives from NORDIL. No robust associations were identified. Finally, interactions between life-style-factors and the CVD-SNP rs4977574 on chromosome 9p21 were evaluated in 24944 MDC-subjects during 15 years follow-up. There were interactions between rs4977574 and smoking on incident CAD (P=0.035) and CVD-mortality (P=0.012). The risk conferred by rs4977574 in never-smokers (n=9642; Hazard-ratio(HR) per risk-allele(CAD)=1.26; 95%CI:1.13-1.40; HR per risk-allele(CVD-mortality)=1.40; 95%CI:1.20-1.63) was attenuated in smokers (n=7000; HR per risk-allele(CAD)=1.05; 95%CI:0.95-1.16; HR per risk-allele(CVD-mortality)=1.08; 95%CI:0.94-1.23). CONCLUSIONS: CVD-genetics identifies subjects with markers of subclinical atherosclerosis, suggesting that early atherosclerosis-prevention may be targeted to such individuals. Smoking attenuates the relative influence of the thus far strongest identified polygenic CVD-risk-locus, implying potential utility of common CVD-genetics in mainly conventional lower-risk subjects. Lipid-polymorphisms may predict statin-induced HDL-increase in women, but eight blood-pressure-SNPs did not affect antihypertensive treatment-response.","abstract_has_math":false,"creators":["Hamrefors, Viktor"],"institution":"Hypertension and Cardiovascular Disease","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014","date_published":"2014","updated_at":"2026-07-24T02:59:49Z","subjects":["Cardiology and Cardiovascular Disease","blood pressure treatment","hypertension","statins","dyslipidemia","cardiovascular prevention","cardiovascular genetics","stroke","coronary artery disease","chromosome 9p21","pharmacogenetics","pharmacogenomics"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["urn:isbn:978-91-87651-40-3"],"render_values":[{"text":"urn:isbn:978-91-87651-40-3","href":null,"code":true}]}]},"links":{"outbound_url":"https://lup.lub.lu.se/record/4253338","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Hamrefors, Viktor"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014"]},{"key":"dc:publisher","label":"Institution","values":["Hypertension and Cardiovascular Disease"]},{"key":"dc:type","label":"Dc Type","values":["thesis/doccomp","info:eu-repo/semantics/doctoralThesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Cardiology and Cardiovascular Disease","blood pressure treatment","hypertension","statins","dyslipidemia","cardiovascular prevention","cardiovascular genetics","stroke","coronary artery disease","chromosome 9p21","pharmacogenetics","pharmacogenomics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://lup.lub.lu.se/record/4253338","urn:isbn:978-91-87651-40-3","https://portal.research.lu.se/files/3843288/4253343.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["GENERAL AIM: To investigate how common single-nucleotide-polymorphisms (SNPs) that associate with cardiovascular disease (CVD) could be used in prevention and treatment of CVD. SUBJECTS: Subjects from the population-based Malmö-Diet-and-Cancer-(MDC)-Study (n=30447) and hypertensives from the Nordic-Diltiazem-(NORDIL)-Study (n=10881). METHODS AND RESULTS: A nine-SNP-lipid-genetic-risk-score was related to fluvastatin treatment-response in 395 MDC subjects with asymptomatic carotid atherosclerosis. In women, a higher score (conferring unfavorable baseline-lipid-levels) correlated with HDL-increase (P=0.001), explaining 11.6-12.9% of the variance in HDL-change. A 13-SNP-myocardial-infarction-(MI)-genetic-risk-score was related to carotid atherosclerosis-markers in 4022 MDC-subjects. The MI-gene-score associated with carotid-bulb-intima-media-thickness (IMT) (beta=0.038 standard deviations of IMT per MI-gene-score-quintile; P-trend=0.005) and plaque (odds-ratio per MI-gene-score-quintile=1.11; 95% confidence interval (CI):1.04-1.18; P=0.001) in multivariable models. It was tested if eight blood-pressure-associated SNPs affected antihypertensive treatment-response in 3863 Swedish hypertensives from NORDIL. No robust associations were identified. Finally, interactions between life-style-factors and the CVD-SNP rs4977574 on chromosome 9p21 were evaluated in 24944 MDC-subjects during 15 years follow-up. There were interactions between rs4977574 and smoking on incident CAD (P=0.035) and CVD-mortality (P=0.012). The risk conferred by rs4977574 in never-smokers (n=9642; Hazard-ratio(HR) per risk-allele(CAD)=1.26; 95%CI:1.13-1.40; HR per risk-allele(CVD-mortality)=1.40; 95%CI:1.20-1.63) was attenuated in smokers (n=7000; HR per risk-allele(CAD)=1.05; 95%CI:0.95-1.16; HR per risk-allele(CVD-mortality)=1.08; 95%CI:0.94-1.23). CONCLUSIONS: CVD-genetics identifies subjects with markers of subclinical atherosclerosis, suggesting that early atherosclerosis-prevention may be targeted to such individuals. Smoking attenuates the relative influence of the thus far strongest identified polygenic CVD-risk-locus, implying potential utility of common CVD-genetics in mainly conventional lower-risk subjects. Lipid-polymorphisms may predict statin-induced HDL-increase in women, but eight blood-pressure-SNPs did not affect antihypertensive treatment-response."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:source","label":"Dc Source","values":["Lund University Faculty of Medicine Doctoral Dissertation Series; 2014:16 (2014)","ISSN: 1652-8220"]},{"key":"dc:title","label":"Title","values":["Cardiovascular Risk Genes in Prevention and Treatment Response"]}]}],"canonical_facts":{"dc:creator":["Hamrefors, Viktor"],"dc:date":["2014"],"dc:description":["GENERAL AIM: To investigate how common single-nucleotide-polymorphisms (SNPs) that associate with cardiovascular disease (CVD) could be used in prevention and treatment of CVD. SUBJECTS: Subjects from the population-based Malmö-Diet-and-Cancer-(MDC)-Study (n=30447) and hypertensives from the Nordic-Diltiazem-(NORDIL)-Study (n=10881). METHODS AND RESULTS: A nine-SNP-lipid-genetic-risk-score was related to fluvastatin treatment-response in 395 MDC subjects with asymptomatic carotid atherosclerosis. In women, a higher score (conferring unfavorable baseline-lipid-levels) correlated with HDL-increase (P=0.001), explaining 11.6-12.9% of the variance in HDL-change. A 13-SNP-myocardial-infarction-(MI)-genetic-risk-score was related to carotid atherosclerosis-markers in 4022 MDC-subjects. The MI-gene-score associated with carotid-bulb-intima-media-thickness (IMT) (beta=0.038 standard deviations of IMT per MI-gene-score-quintile; P-trend=0.005) and plaque (odds-ratio per MI-gene-score-quintile=1.11; 95% confidence interval (CI):1.04-1.18; P=0.001) in multivariable models. It was tested if eight blood-pressure-associated SNPs affected antihypertensive treatment-response in 3863 Swedish hypertensives from NORDIL. No robust associations were identified. Finally, interactions between life-style-factors and the CVD-SNP rs4977574 on chromosome 9p21 were evaluated in 24944 MDC-subjects during 15 years follow-up. There were interactions between rs4977574 and smoking on incident CAD (P=0.035) and CVD-mortality (P=0.012). The risk conferred by rs4977574 in never-smokers (n=9642; Hazard-ratio(HR) per risk-allele(CAD)=1.26; 95%CI:1.13-1.40; HR per risk-allele(CVD-mortality)=1.40; 95%CI:1.20-1.63) was attenuated in smokers (n=7000; HR per risk-allele(CAD)=1.05; 95%CI:0.95-1.16; HR per risk-allele(CVD-mortality)=1.08; 95%CI:0.94-1.23). CONCLUSIONS: CVD-genetics identifies subjects with markers of subclinical atherosclerosis, suggesting that early atherosclerosis-prevention may be targeted to such individuals. Smoking attenuates the relative influence of the thus far strongest identified polygenic CVD-risk-locus, implying potential utility of common CVD-genetics in mainly conventional lower-risk subjects. Lipid-polymorphisms may predict statin-induced HDL-increase in women, but eight blood-pressure-SNPs did not affect antihypertensive treatment-response."],"dc:format":["application/pdf"],"dc:identifier":["https://lup.lub.lu.se/record/4253338","urn:isbn:978-91-87651-40-3","https://portal.research.lu.se/files/3843288/4253343.pdf"],"dc:language":["eng"],"dc:publisher":["Hypertension and Cardiovascular Disease"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Lund University Faculty of Medicine Doctoral Dissertation Series; 2014:16 (2014)","ISSN: 1652-8220"],"dc:subject":["Cardiology and Cardiovascular Disease","blood pressure treatment","hypertension","statins","dyslipidemia","cardiovascular prevention","cardiovascular genetics","stroke","coronary artery disease","chromosome 9p21","pharmacogenetics","pharmacogenomics"],"dc:title":["Cardiovascular Risk Genes in Prevention and Treatment Response"],"dc:type":["thesis/doccomp","info:eu-repo/semantics/doctoralThesis","text"]},"updated_at":"2026-07-24T02:59:49Z"}