TY  - JOUR
AU  - Schneider, A.E.
AU  - Chen, K.*
AU  - Breitner-Busch, S.
C1  - 73149
C2  - 56930
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 622-624
TI  - The pathogenetic link between ozone pollution and cardiovascular disease.
JO  - J. Am. Coll. Cardiol.
VL  - 85
IS  - 6
PB  - Elsevier Science Inc
PY  - 2025
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Background: Conventional low-density lipoprotein cholesterol (LDL-C) quantification includes cholesterol attributable to lipoprotein(a) (Lp(a)-C) due to their overlapping densities. Objectives: The purposes of this study were to compare the association between LDL-C and LDL-C corrected for Lp(a)-C (LDLLp(a)corr) with incident coronary heart disease (CHD) in the general population and to investigate whether concomitant Lp(a) values influence the association of LDL-C or apolipoprotein B (apoB) with coronary events. Methods: Among 68,748 CHD-free subjects at baseline LDLLp(a)corr was calculated as “LDL-C—Lp(a)-C,” where Lp(a)-C was 30% or 17.3% of total Lp(a) mass. Fine and Gray competing risk-adjusted models were applied for the association between the outcome incident CHD and: 1) LDL-C and LDLLp(a)corr in the total sample; and 2) LDL-C and apoB after stratification by Lp(a) mass (≥/<90th percentile). Results: Similar risk estimates for incident CHD were found for LDL-C and LDL-CLp(a)corr30 or LDL-CLp(a)corr17.3 (subdistribution HR with 95% CI) were 2.73 (95% CI: 2.34-3.20) vs 2.51 (95% CI: 2.15-2.93) vs 2.64 (95% CI: 2.26-3.10), respectively (top vs bottom fifth; fully adjusted models). Categorization by Lp(a) mass resulted in higher subdistribution HRs for uncorrected LDL-C and incident CHD at Lp(a) ≥90th percentile (4.38 [95% CI: 2.08-9.22]) vs 2.60 [95% CI: 2.21-3.07]) at Lp(a) <90th percentile (top vs bottom fifth; Pinteraction0.39). In contrast, apoB risk estimates were lower in subjects with higher Lp(a) mass (2.43 [95% CI: 1.34-4.40]) than in Lp(a) <90th percentile (3.34 [95% CI: 2.78-4.01]) (Pinteraction0.49). Conclusions: Correction of LDL-C for its Lp(a)-C content provided no meaningful information on CHD-risk estimation at the population level. Simple categorization of Lp(a) mass (≥/<90th percentile) influenced the association between LDL-C or apoB with future CHD mostly at higher Lp(a) levels.
AU  - Arnold, N.*
AU  - Blaum, C.*
AU  - Goßling, A.*
AU  - Brunner, F.J.*
AU  - Bay, B.*
AU  - Zeller, T.*
AU  - Ferrario, M.M.*
AU  - Brambilla, P.*
AU  - Cesana, G.*
AU  - Leoni, V.*
AU  - Palmieri, L.*
AU  - Donfrancesco, C.*
AU  - Ojeda, F.*
AU  - Linneberg, A.*
AU  - Söderberg, S.*
AU  - Iacoviello, L.*
AU  - Gianfagna, F.*
AU  - Costanzo, S.*
AU  - Sans, S.*
AU  - Veronesi, G.*
AU  - Thorand, B.
AU  - Peters, A.
AU  - Tunstall-Pedoe, H.*
AU  - Kee, F.*
AU  - Salomaa, V.*
AU  - Schnabel, R.B.*
AU  - Kuulasmaa, K.*
AU  - Blankenberg, S.*
AU  - Waldeyer, C.*
AU  - Koenig, W.*
C1  - 70962
C2  - 55839
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 165-177
TI  - Impact of lipoprotein(a) level on low-density lipoprotein cholesterol– or apolipoprotein B–related risk of coronary heart disease.
JO  - J. Am. Coll. Cardiol.
VL  - 84
IS  - 2
PB  - Elsevier Science Inc
PY  - 2024
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Background: The association between nonoptimal temperatures and cardiovascular mortality risk is recognized. However, a comprehensive global assessment of this burden is lacking. Objectives: The goal of this study was to assess global cardiovascular mortality burden attributable to nonoptimal temperatures and investigate spatiotemporal trends. Methods: Using daily cardiovascular deaths and temperature data from 32 countries, a 3-stage analytical approach was applied. First, location-specific temperature–mortality associations were estimated, considering nonlinearity and delayed effects. Second, a multivariate meta-regression model was developed between location-specific effect estimates and 5 meta-predictors. Third, cardiovascular deaths associated with nonoptimal, cold, and hot temperatures for each global grid (55 km × 55 km resolution) were estimated, and temporal trends from 2000 to 2019 were explored. Results: Globally, 1,801,513 (95% empirical CI: 1,526,632-2,202,831) annual cardiovascular deaths were associated with nonoptimal temperatures, constituting 8.86% (95% empirical CI: 7.51%-12.32%) of total cardiovascular mortality corresponding to 26 deaths per 100,000 population. Cold-related deaths accounted for 8.20% (95% empirical CI: 6.74%-11.57%), whereas heat-related deaths accounted for 0.66% (95% empirical CI: 0.49%-0.98%). The mortality burden varied significantly across regions, with the highest excess mortality rates observed in Central Asia and Eastern Europe. From 2000 to 2019, cold-related excess death ratios decreased, while heat-related ratios increased, resulting in an overall decline in temperature-related deaths. Southeastern Asia, Sub-Saharan Africa, and Oceania observed the greatest reduction, while Southern Asia experienced an increase. The Americas and several regions in Asia and Europe displayed fluctuating temporal patterns. Conclusions: Nonoptimal temperatures substantially contribute to cardiovascular mortality, with heterogeneous spatiotemporal patterns. Effective mitigation and adaptation strategies are crucial, especially given the increasing heat-related cardiovascular deaths amid climate change.
AU  - Hundessa, S.*
AU  - Huang, W.*
AU  - Zhao, Q.*
AU  - Wu, Y.*
AU  - Wen, B.*
AU  - Alahmad, B.*
AU  - Armstrong, B.*
AU  - Gasparrini, A.*
AU  - Sera, F.*
AU  - Tong, S.*
AU  - Madureira, J.*
AU  - Kyselý, J.*
AU  - Schwartz, J.*
AU  - Vicedo-Cabrera, A.M.*
AU  - Hales, S.*
AU  - Johnson, A.*
AU  - Li, S.*
AU  - Guo, Y.*
AU  - Jaakkola, J.J.K.*
AU  - Ryti, N.*
AU  - Urban, A.*
AU  - Tobias, A.*
AU  - Royé, D.*
AU  - Lavigne, E.*
AU  - Ragettli, M.S.*
AU  - Åström, C.*
AU  - Raz, R.*
AU  - Pascal, M.*
AU  - Kan, H.*
AU  - Goodman, P.*
AU  - Zeka, A.*
AU  - Hashizume, M.*
AU  - Diaz, M.H.*
AU  - Seposo, X.*
AU  - Nunes, B.*
AU  - Kim, H.*
AU  - Lee, W.*
AU  - Iñiguez, C.*
AU  - Guo, Y.L.*
AU  - Pan, S.C.*
AU  - Zanobetti, A.*
AU  - Dang, T.N.*
AU  - Van Dung, D.*
AU  - MCC Collaborators (Schneider, A.E.)
AU  - Entezari, A.*
AU  - Analitis, A.*
AU  - Forsberg, B.*
AU  - Ameling, C.*
AU  - Houthuijs, D.*
AU  - Indermitte, E.*
AU  - Mayvaneh, F.*
AU  - Acquaotta, F.*
AU  - de'Donato, F.*
AU  - Carrasco-Escobar, G.*
AU  - Orru, H.*
AU  - Katsouyanni, K.*
AU  - de Sousa Zanotti Stagliorio Coélho, M.*
AU  - Ortega, N.V.*
AU  - Scovronick, N.*
AU  - Michelozzi, P.*
AU  - Correa, P.M.*
AU  - Nascimento Saldiva, P.H.*
AU  - Abrutzky, R.*
AU  - Osorio, S.*
AU  - Colistro, V.*
AU  - Huber, V.*
AU  - Honda, Y.*
AU  - Kim, Y.*
AU  - Bell, M.*
AU  - Xu, R.*
AU  - Yang, Z.*
AU  - Roradeh, H.*
AU  - Félix Arellano, E.E.*
AU  - Rao, S.*
AU  - Carlos Chua, P.L.*
AU  - da Silva, S.d.N.P.*
AU  - De la Cruz Valencia, C.*
C1  - 70974
C2  - 55845
SP  - 2276-2287
TI  - Global and regional cardiovascular mortality attributable to nonoptimal temperatures over time.
JO  - J. Am. Coll. Cardiol.
VL  - 83
IS  - 23
PY  - 2024
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND: Lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood. OBJECTIVES: The purpose of this study was to investigate the short-term effects of lower air temperature and cold spells on the risk of hospitalization for MI in Sweden. METHODS: This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature (1 km2 resolution) was estimated using machine learning, and percentiles of daily temperatures experienced by individuals in the same municipality were used as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least 2 consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating conditional logistic regression models with distributed lag nonlinear models using lag 0 to 1 (immediate) and 2 to 6 days (delayed) was used to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). RESULTS: A decrease of 1-unit in percentile temperature at a lag of 2 to 6 days was significantly associated with increased risks of total MI, NSTEMI, and STEMI, with ORs of 1.099 (95% CI: 1.057-1.142), 1.110 (95% CI: 1.060-1.164), and 1.076 (95% CI: 1.004-1.153), respectively. Additionally, cold spells at a lag of 2 to 6 days were significantly associated with increased risks for total MI, NSTEMI, and STEMI, with ORs of 1.077 (95% CI: 1.037-1.120), 1.069 (95% CI: 1.020-1.119), and 1.095 (95% CI: 1.023-1.172), respectively. Conversely, lower air temperature and cold spells at a lag of 0 to 1 days were associated with decreased risks for MI. CONCLUSIONS: This nationwide case-crossover study reveals that short-term exposures to lower air temperature and cold spells are associated with an increased risk of hospitalization for MI at lag 2 to 6 days.
AU  - Ni, W.
AU  - Stafoggia, M.*
AU  - Zhang, S.
AU  - Ljungman, P.*
AU  - Breitner-Busch, S.
AU  - Bont, J.*
AU  - Jernberg, T.*
AU  - Atar, D.*
AU  - Agewall, S.*
AU  - Schneider, A.E.
C1  - 71620
C2  - 56315
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 1149-1159
TI  - Short-term effects of lower air temperature and cold spells on myocardial infarction hospitalizations in Sweden.
JO  - J. Am. Coll. Cardiol.
VL  - 84
IS  - 13
PB  - Elsevier Science Inc
PY  - 2024
SN  - 0735-1097
ER  - 

TY  - JOUR
AU  - Mensah, G.A.*
AU  - Fuster, V.*
AU  - Murray, C.J.L.*
AU  - Roth, G.A.*
AU  - Global Burden of Cardiovascular Diseases and Risks Collaborators (Breitner-Busch, S.)
C1  - 70156
C2  - 55028
SP  - 2350-2473
TI  - Global burden of cardiovascular diseases and risks, 1990-2022.
JO  - J. Am. Coll. Cardiol.
VL  - 82
IS  - 25
PY  - 2023
SN  - 0735-1097
ER  - 

TY  - JOUR
AU  - Schneider, A.E.
AU  - Atar, D.*
AU  - Agewall, S.*
C1  - 67723
C2  - 54031
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 1130-1132
TI  - RESPONSE: Climate change and health: Challenges, opportunities, and the need for action.
JO  - J. Am. Coll. Cardiol.
VL  - 81
IS  - 11
PB  - Elsevier Science Inc
PY  - 2023
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES: This study sought to test the association between the rs9349379 genotype and SCAD. METHODS: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
AU  - Adlam, D.*
AU  - Olson, T.M.*
AU  - Combaret, N.*
AU  - Kovacic, J.C.*
AU  - Iismaa, S.E.*
AU  - Al-Hussani, A.*
AU  - O'Byrne, M.M.*
AU  - Bouajila, S.*
AU  - Georges, A.*
AU  - Mishra, K.*
AU  - Braund, P.S.*
AU  - d’Escamard, V.*
AU  - Huang, S.*
AU  - Margaritis, M.*
AU  - Nelson, C.P.*
AU  - de Andrade, M.*
AU  - Kadian-Dodov, D.*
AU  - Welch, C.A.*
AU  - Bouatia-Naji, N.*
AU  - CARDIoGRAMplusC4D Consortium (Gieger, C.
AU  - Meitinger, T.*
AU  - Peters, A.)
C1  - 55791
C2  - 46588
SP  - 58-66
TI  - Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection.
JO  - J. Am. Coll. Cardiol.
VL  - 73
IS  - 1
PY  - 2019
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND Subclinical changes on the electrocardiogram are risk factors for cardiovascular mortality. Recognition and knowledge of electrolyte associations in cardiac electrophysiology are based on only in vitro models and observations in patients with severe medical conditions.OBJECTIVES This study sought to investigate associations between serum electrolyte concentrations and changes in cardiac electrophysiology in the general population.METHODS Summary results collected from 153,014 individuals (54.4% women; mean age 55.1 +/- 12.1 years) from 33 studies (of 5 ancestries) were meta-analyzed. Linear regression analyses examining associations between electrolyte concentrations (mmol/l of calcium, potassium, sodium, and magnesium), and electrocardiographic intervals (RR, QT, QRS, JT, and PR intervals) were performed. The study adjusted for potential confounders and also stratified by ancestry, sex, and use of antihypertensive drugs.RESULTS Lower calcium was associated with longer QT intervals (-11.5 ms; 99.75% confidence interval [CI]: -13.7 to -9.3) and JT duration, with sex-specific effects. In contrast, higher magnesium was associated with longer QT intervals (7.2 ms; 99.75% CI: 1.3 to 13.1) and JT. Lower potassium was associated with longer QT intervals (-2.8 ms; 99.75% CI: -3.5 to -2.0), JT, QRS, and PR durations, but all potassium associations were driven by use of antihypertensive drugs. No physiologically relevant associations were observed for sodium or RR intervals.CONCLUSIONS The study identified physiologically relevant associations between electrolytes and electrocardiographic intervals in a large-scale analysis combining cohorts from different settings. The results provide insights for further cardiac electrophysiology research and could potentially influence clinical practice, especially the association between calcium and QT duration, by which calcium levels at the bottom 2% of the population distribution led to clinically relevant QT prolongation by >5 ms.
AU  - Noordam, R.*
AU  - Young, W.J.*
AU  - Salman, R.*
AU  - Kanters, J.K.*
AU  - van den Berg, M.E.*
AU  - van Heemst, D.*
AU  - Lin, H.J.*
AU  - Barreto, S.M.*
AU  - Biggs, M.L.*
AU  - Biino, G.*
AU  - Catamo, E.*
AU  - Concas, M.P.*
AU  - Ding, J.*
AU  - Evans, D.S.*
AU  - Foco, L.*
AU  - Grarup, N.*
AU  - Lyytikäinen, L.P.*
AU  - Mangino, M.*
AU  - Mei, H.*
AU  - van der Most, P.J.*
AU  - Müller-Nurasyid, M.
AU  - Nelson, C.P.*
AU  - Qian, Y.*
AU  - Repetto, L.*
AU  - Said, M.A.*
AU  - Shah, N.*
AU  - Schramm, K.
AU  - Vidigal, P.G.*
AU  - Weiss, S.*
AU  - Yao, J.*
AU  - Zilhao, N.R.*
AU  - Brody, J.A.*
AU  - Braund, P.S.*
AU  - Brumat, M.*
AU  - Campana, E.*
AU  - Christofidou, P.*
AU  - Caulfield, M.J.*
AU  - de Grandi, A.*
AU  - Dominiczak, A.F.*
AU  - Doney, A.S.F.*
AU  - Eiriksdottir, G.*
AU  - Ellervik, C.*
AU  - Giatti, L.*
AU  - Gögele, M.*
AU  - Graff, C.*
AU  - Guo, X.*
AU  - van der Harst, P.*
AU  - Joshi, P.K.*
AU  - Kähönen, M.*
AU  - Kestenbaum, B.*
AU  - Lima-Costa, M.F.*
AU  - Linneberg, A.*
AU  - Maan, A.C.*
AU  - Meitinger, T.
AU  - Padmanabhan, S.*
AU  - Pattaro, C.*
AU  - Peters, A.
AU  - Petersmann, A.*
AU  - Sever, P.*
AU  - Sinner, M.F.*
AU  - Shen, X.*
AU  - Stanton, A.*
AU  - Strauch, K.
AU  - Soliman, E.Z.*
AU  - Tarasov, K.V.*
AU  - Taylor, K.D.*
AU  - Thio, C.H.L.*
AU  - Uitterlinden, A.G.*
AU  - Vaccargiu, S.*
AU  - Waldenberger, M.
AU  - Robino, A.*
AU  - Correa, A.*
AU  - Cucca, F.*
AU  - Cummings, S.R.*
AU  - Dörr, M.*
AU  - Girotto, G.*
AU  - Gudnason, V.*
AU  - Hansen, T.*
AU  - Heckbert, S.R.*
AU  - Juhl, C.R.*
AU  - Kääb, S.*
AU  - Lehtimäki, T.*
AU  - Liu, Y.*
AU  - Lotufo, P.A.*
AU  - Palmer, C.N.A.*
AU  - Pirastu, M.*
AU  - Pramstaller, P.P.*
AU  - Ribeiro, A.L.P.*
AU  - Rotter, J.I.*
AU  - Samani, N.J.*
AU  - Snieder, H.*
AU  - Spector, T.D.*
AU  - Stricker, B.H.*
AU  - Verweij, N.*
AU  - Wilson, J.F.*
AU  - Wilson, J.G.*
AU  - Jukema, J.W.*
AU  - Tinker, A.*
AU  - Newton-Cheh, C.H.*
AU  - Sotoodehnia, N.*
C1  - 56351
C2  - 47019
CY  - Ste 800, 230 Park Ave, New York, Ny 10169 Usa
SP  - 3118-3131
TI  - Effects of calcium, magnesium, and potassium concentrations on ventricular repolarization in unselected individuals.
JO  - J. Am. Coll. Cardiol.
VL  - 73
IS  - 24
PB  - Elsevier Science Inc
PY  - 2019
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - The primary objective of this study was to analyze the most up-to-date evidence regarding whether and how blood sugar regulation influences cardiovascular health promotion and disease prevention by carrying out an umbrella review. Three separate, systematic literature searches identified 2,343 papers in total. Overall, 44 studies were included for data extraction and analysis. The included systematic reviews and meta-analyses published between January 1, 2016, and December 31, 2017, were of good to very good quality (median Overview Quality Assessment Questionnaire score = 17). Identified evidence suggests that cardiovascular disease (CVD) prevention services should consider regulation of blood glucose as a key target for intervention. Furthermore, the recommendations for effective intervention and service development/training described here for prevention of CVD should be adopted into evidence-based practice guidelines. Multidisciplinary teams should be formed to deliver multicomponent interventions in community-based settings. There may be substantial opportunities for integrating CVD and diabetes prevention services.
AU  - Schwarz, P.E.
AU  - Timpel, P.*
AU  - Harst, L.*
AU  - Greaves, C.J.*
AU  - Ali, M.K.*
AU  - Lambert, J.C.*
AU  - Weber, M.B.*
AU  - Almedawar, M.M.*
AU  - Morawietz, H.*
C1  - 54473
C2  - 45604
CY  - 360 Park Ave South, New York, Ny 10010-1710 Usa
SP  - 1829-1844
TI  - Blood sugar regulation for cardiovascular health promotion and disease prevention JACC health promotion series.
JO  - J. Am. Coll. Cardiol.
VL  - 72
IS  - 15
PB  - Elsevier Science Inc
PY  - 2018
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Background Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. Objectives This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. Methods In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. Results We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10−4 with a range of other diseases/traits. Conclusions We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
AU  - Webb, T.R.*
AU  - Erdmann, J.*
AU  - Stirrups, K.E.*
AU  - Stitziel, N.O.*
AU  - Masca, N.G.D.*
AU  - Jansen, H.*
AU  - Kanoni, S.*
AU  - Nelson, C.P.*
AU  - Ferrario, P.G.*
AU  - König, I.R.*
AU  - Eicher, J.D.*
AU  - Johnson, A.D.*
AU  - Hamby, S.E.*
AU  - Betsholtz, C.*
AU  - Ruusalepp, A.*
AU  - Franzén, O.*
AU  - Schadt, E.E.*
AU  - Bjorkegren, J.L.M.*
AU  - Weeke, P.E.*
AU  - Auer, P.L.*
AU  - Schick, U.M.*
AU  - Lu, Y.*
AU  - Zhang, H.*
AU  - Dubé, M.-P.*
AU  - Goel, A.*
AU  - Farrall, M.*
AU  - Peloso, G.M.*
AU  - Meisinger, C.
AU  - Peters, A.
AU  - van Iperen, E.*
AU  - Kruppa, J.*
AU  - Mahajan, A.*
AU  - Scott, R.A.*
AU  - Willenborg, C.*
AU  - Braund, P.S.*
AU  - van Capelleveen, J.C.*
AU  - Doney, A.S.F.*
AU  - Donnelly, L.A.*
AU  - Asselta, R.*
AU  - Merlini, P.A.*
AU  - Duga, S.*
AU  - Marziliano, N.*
AU  - Denny, J.C.*
AU  - Shaffer, C.*
AU  - El-Mokhtari, N.E.*
AU  - Franke, A.*
AU  - Heilmann, S.*
AU  - Hengstenberg, C.*
AU  - Hoffmann, P.*
AU  - Holmen, O.L.*
AU  - Hveem, K.*
AU  - Jansson, J.H.*
AU  - Jöckel, K.H.*
AU  - Kessler, T.*
AU  - Kriebel, J.
AU  - Müller-Nurasyid, M.
AU  - Strauch, K.
AU  - Waldenberger, M.
AU  - Meitinger, T.
AU  - Kathiresan, S.*
C1  - 50547
C2  - 42409
CY  - New York
SP  - 823-836
TI  - Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease.
JO  - J. Am. Coll. Cardiol.
VL  - 69
IS  - 7
PB  - Elsevier Science Inc
PY  - 2017
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND: Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. OBJECTIVES: Through a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). METHODS: This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. RESULTS: Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. CONCLUSIONS: Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.
AU  - Keenan, T.*
AU  - Zhao, W.*
AU  - Rasheed, A.*
AU  - Ho, W.K.*
AU  - Malik, R.*
AU  - Felix, J.F.*
AU  - Young, R.*
AU  - Shah, N.*
AU  - Samuel, M.A.*
AU  - Sheikh, N.*
AU  - Mucksavage, M.L.*
AU  - Shah, O.*
AU  - Li, J.*
AU  - Morley, M.*
AU  - Laser, A.
AU  - Mallick, N.H.*
AU  - Zaman, K.S.*
AU  - Ishaq, M.*
AU  - Rasheed, S.Z.*
AU  - Memon, F.U.*
AU  - Ahmed, F.*
AU  - Hanif, B.*
AU  - Lakhani, M.S.*
AU  - Fahim, M.*
AU  - Shardha, N.K.*
AU  - Ahmed, N.*
AU  - Mahmood, K.*
AU  - Iqbal, W.*
AU  - Akhtar, S.*
AU  - Raheel, R.*
AU  - O'Donnell, C.J.*
AU  - Hengstenberg, C.*
AU  - Marz, W.*
AU  - Kathiresan, S.*
AU  - Samani, N.*
AU  - Goel, A.*
AU  - Hopewell, J.C.*
AU  - Chambers, J.*
AU  - Cheng, Y.C.*
AU  - Sharma, P.*
AU  - Yang, Q.*
AU  - Rosand, J.*
AU  - Boncoraglio, G.B.*
AU  - Kazmi, S.U.*
AU  - Hakonarson, H.*
AU  - Köttgen, A.*
AU  - Kalogeropoulos, A.*
AU  - Frossard, P.*
AU  - Kamal, A.K.*
AU  - Dichgans, M.*
AU  - Cappola, T.P.*
AU  - Reilly, M.P.*
AU  - Danesh, J.*
AU  - Rader, D.J.*
AU  - Voight, B.F.*
AU  - Saleheen, D.*
C1  - 47788
C2  - 39476
SP  - 407-416
TI  - Causal assessment of serum urate levels in cardiometabolic diseases through a mendelian randomization study.
JO  - J. Am. Coll. Cardiol.
VL  - 67
IS  - 4
PY  - 2016
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death. OBJECTIVES: This meta-analysis sought to gain insights into the genetic determinants of myocardial mass. METHODS: We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment. RESULTS: We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p < 1 × 10(-8). These loci are enriched in regions of open chromatin, histone modifications, and transcription factor binding, suggesting that they represent regions of the genome that are actively transcribed in the human heart. Pathway analyses provided evidence that these loci play a role in cardiac hypertrophy. We further highlighted 67 candidate genes at the identified loci that are preferentially expressed in cardiac tissue and associated with cardiac abnormalities in Drosophila melanogaster and Mus musculus. We validated the regulatory function of a novel variant in the SCN5A/SCN10A locus in vitro and in vivo. CONCLUSIONS: Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
AU  - van der Harst, P.*
AU  - van Setten, J.*
AU  - Verweij, N.*
AU  - Vogler, G.*
AU  - Franke, L.*
AU  - Maurano, M.T.*
AU  - Wang, X.*
AU  - Mateo Leach, I.*
AU  - Eijgelsheim, M.*
AU  - Sotoodehnia, N.*
AU  - Hayward, C.*
AU  - Sorice, R.*
AU  - Meirelles, O.*
AU  - Lyytikäinen, L.-P.*
AU  - Polasek, O.*
AU  - Tanaka, T.*
AU  - Arking, D.E.*
AU  - Ulivi, S.*
AU  - Trompet, S.*
AU  - Müller-Nurasyid, M.
AU  - Smith, A.V.*
AU  - Dörr, M.*
AU  - Kerr, K.F.*
AU  - Magnani, J.W.*
AU  - Del Greco M, F.*
AU  - Zhang, W.*
AU  - Nolte, I.M.*
AU  - Silva, C.T.*
AU  - Padmanabhan, S.*
AU  - Tragante, V.*
AU  - Esko, T.*
AU  - Abecasis, G.R.*
AU  - Adriaens, M.E.*
AU  - Andersen, K.*
AU  - Barnett, P.*
AU  - Bis, J.C.*
AU  - Bodmer, R.*
AU  - Buckley, B.M.*
AU  - Campbell, H.*
AU  - Cannon, M.V.*
AU  - Chakravarti, A.*
AU  - Chen, L.Y.*
AU  - Delitala, A.*
AU  - Devereux, R.B.*
AU  - Doevendans, P.A.*
AU  - Dominiczak, A.F.*
AU  - Ferrucci, L.*
AU  - Ford, I.*
AU  - Gieger, C.
AU  - Harris, T.B.*
AU  - Haugen, E.*
AU  - Heinig, M.
AU  - Hernandez, D.G.*
AU  - Hillege, H.L.*
AU  - Hirschhorn, J.N.*
AU  - Hofman, A.*
AU  - Hubner, N.*
AU  - Hwang, S.J.*
AU  - Iorio, A.*
AU  - Kähönen, M.*
AU  - Kellis, M.*
AU  - Kolcic, I.*
AU  - Kooner, I.K.*
AU  - Kooner, J.S.*
AU  - Kors, J.A.*
AU  - Lakatta, E.G.*
AU  - Lage, K.*
AU  - Launer, L.J.*
AU  - Levy, D.*
AU  - Lundby, A.*
AU  - Macfarlane, P.W.*
AU  - May, D.*
AU  - Meitinger, T.
AU  - Metspalu, A.*
AU  - Nappo, S.*
AU  - Naitza, S.*
AU  - Neph, S.*
AU  - Nord, A.S.*
AU  - Nutile, T.*
AU  - Okin, P.M.*
AU  - Olsen, J.V.*
AU  - Oostra, B.A.*
AU  - Penninger, J.M.*
AU  - Pennacchio, L.A.*
AU  - Pers, T.H.*
AU  - Perz, S.
AU  - Peters, A.
AU  - Pinto, Y.M.*
AU  - Pfeufer, A.
AU  - Pilia, M.G.*
AU  - Pramstaller, P.P.*
AU  - Prins, B.P.*
AU  - Raitakari, O.T.*
AU  - Raychaudhuri, S.*
AU  - Rice, K.M.*
AU  - Rossin, E.J.*
AU  - Rotter, J.I.*
AU  - Schafer, S.*
AU  - Schlessinger, D.*
AU  - Schmidt, C.O.*
AU  - Sehmi, J.*
AU  - Sillje, H.H.W.*
AU  - Sinagra, G.*
AU  - Sinner, M.F.*
AU  - Slowikowski, K.*
AU  - Soliman, E.Z.*
AU  - Spector, T.D.*
AU  - Spiering, W.*
AU  - Stamatoyannopoulos, J.A.*
AU  - Stolk, R.P.*
AU  - Strauch, K.
AU  - Tan, S.T.*
AU  - Tarasov, K.V.*
AU  - Trinh, B.*
AU  - Uitterlinden, A.G.*
AU  - van den Boogaard, M.J.*
AU  - van Duijn, C.M.*
AU  - van Gilst, W.H.*
AU  - Viikari, J.S.*
AU  - Visscher, P.M.*
AU  - Vitart, V.*
AU  - Völker, U.*
AU  - Waldenberger, M.
AU  - Weichenberger, C.X.*
AU  - Westra, H.J.*
AU  - Wijmenga, C.*
AU  - Wolffenbuttel, B.H.*
AU  - Yang, J.*
AU  - Bezzina, C.R.*
AU  - Munroe, P.B.*
AU  - Snieder, H.*
AU  - Wright, A.F.*
AU  - Rudan, I.*
AU  - Boyer, L.A.*
AU  - Asselbergs, F.W.*
AU  - van Veldhuisen, D.J.*
AU  - Stricker, B.H.*
AU  - Psaty, B.M.*
AU  - Ciullo, M.*
AU  - Sanna, S.*
AU  - Lehtimäki, T.*
AU  - Wilson, J.F.*
AU  - Bandinelli, S.*
AU  - Alonso, A.*
AU  - Gasparini, P.*
AU  - Jukema, J.W.*
AU  - Kääb, S.*
AU  - Gudnason, V.*
AU  - Felix, S.B.*
AU  - Heckbert, S.R.*
AU  - de Boer, R.A.*
AU  - Newton-Cheh, C.*
AU  - Hicks, A.A.*
AU  - Chambers, J.C.*
AU  - Jamshidi, Y.*
AU  - Visel, A.*
AU  - Christoffels, V.M.*
AU  - Isaacs, A.*
AU  - Samani, N.J.*
AU  - de Bakker, P.I.*
C1  - 49545
C2  - 40705
CY  - New York
SP  - 1435-1448
TI  - 52 Genetic loci influencing myocardial mass.
JO  - J. Am. Coll. Cardiol.
VL  - 68
IS  - 13
PB  - Elsevier Science Inc
PY  - 2016
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS: We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS: Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
AU  - van der Laan, S.W.*
AU  - Fall, T.*
AU  - Soumare, A.*
AU  - Teumer, A.*
AU  - Sedaghat, S.*
AU  - Baumert, J.J.
AU  - Zabaneh, D.*
AU  - van Setten, J.*
AU  - Isgum, I.*
AU  - Galesloot, T.E.*
AU  - Arpegård, J.*
AU  - Amouyel, P.*
AU  - Trompet, S.*
AU  - Waldenberger, M.
AU  - Dörr, M.*
AU  - Magnusson, P.K.*
AU  - Giedraitis, V.*
AU  - Larsson, A.*
AU  - Morris, A.P.*
AU  - Felix, J.F.*
AU  - Morrison, A.C.*
AU  - Franceschini, N.*
AU  - Bis, J.C.*
AU  - Kavousi, M.*
AU  - O'Donnell, C.*
AU  - Drenos, F.*
AU  - Tragante, V.*
AU  - Munroe, P.B.*
AU  - Malik, R.*
AU  - Dichgans, M.*
AU  - Worrall, B.B.*
AU  - Erdmann, J.*
AU  - Nelson, C.P.*
AU  - Samani, N.J.*
AU  - Schunkert, H.*
AU  - Marchini, J.*
AU  - Patel, R.S.*
AU  - Hingorani, A.D.*
AU  - Lind, L.*
AU  - Pedersen, N.L.*
AU  - de Graaf, J.*
AU  - Kiemeney, L.A.*
AU  - Baumeister, S.E.*
AU  - Franco, O.H.*
AU  - Hofman, A.*
AU  - Uitterlinden, A.G.*
AU  - Koenig, W.*
AU  - Meisinger, C.
AU  - Peters, A.
AU  - Thorand, B.
AU  - Jukema, J.W.*
AU  - Eriksen, B.O.*
AU  - Toft, I.*
AU  - Wilsgaard, T.*
AU  - Onland-Moret, N.C.*
AU  - van der Schouw, Y.T.*
AU  - Debette, S.*
AU  - Kumari, M.*
AU  - Svensson, P.*
AU  - van der Harst, P.*
AU  - Kivimaki, M.*
AU  - Keating, B.J.*
AU  - Sattar, N.*
AU  - Dehghan, A.*
AU  - Reiner, A.P.*
AU  - Ingelsson, E.*
AU  - den Ruijter, H.M.*
AU  - de Bakker, P.I.*
AU  - Pasterkamp, G.*
AU  - Ärnlöv, J.*
AU  - Holmes, M.V.*
AU  - Asselbergs, F.W.*
C1  - 49329
C2  - 41755
CY  - New York
SP  - 934-945
TI  - Cystatin C and cardiovascular disease: A mendelian randomization study.
JO  - J. Am. Coll. Cardiol.
VL  - 68
IS  - 9
PB  - Elsevier Science Inc
PY  - 2016
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - While acute myocardial infarction mortality declines, patients continue to face reinfarction and/or heart failure. The immune system, which intimately interacts with healthy and diseased tissues through resident and recruited leukocytes, is a central interface for a global host response to ischemia. Pathways that enhance the systemic leukocyte supply may be potential therapeutic targets. Pre-clinically, imaging helps to identify immunity's decision nodes, which may serve as such targets. In translating the rapidly-expanding pre-clinical data on immune activity, the difficulty of obtaining multiple clinical tissue samples from involved organs is an obstacle that whole-body imaging can help overcome. In patients, molecular and cellular imaging can be integrated with blood-based diagnostics to assess the translatability of discoveries, including the activation of hematopoietic tissues after myocardial infarction, and serve as an endpoint in clinical trials. In this review, we discuss these concepts while focusing on imaging immune activity in organs involved in ischemic heart disease.
AU  - Nahrendorf, M.*
AU  - Frantz, S.*
AU  - Swirski, F.K.*
AU  - Mulder, W.J.*
AU  - Randolph, G.J.*
AU  - Ertl, G.*
AU  - Ntziachristos, V.
AU  - Piek, J.J.*
AU  - Stroes, E.S.*
AU  - Schwaiger, M.*
AU  - Mann, D.L.*
AU  - Fayad, Z.A.*
C1  - 44433
C2  - 36836
CY  - New York
SP  - 1583-1591
TI  - Imaging systemic inflammatory networks in ischemic heart disease.
JO  - J. Am. Coll. Cardiol.
VL  - 65
IS  - 15
PB  - Elsevier Science Inc
PY  - 2015
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - BACKGROUND: A puzzling feature of the long QT syndrome (LQTS) is that family members carrying the same mutation often have divergent symptoms and clinical outcomes. OBJECTIVES: This study tested the hypothesis that vagal and sympathetic control, as assessed by spectral analysis of spontaneous beat-to-beat variability of RR and QT intervals from standard 24-h electrocardiogram Holter recordings, could modulate the severity of LQTS type 1 (LQT1) in 46 members of a South-African LQT1 founder population carrying the clinically severe KCNQ1 A341V mutation. METHODS: Nonmutation carriers (NMCs) (n = 14) were compared with mutation carriers (MCs) (n = 32), 22 with and 10 without major symptoms. We assessed the effect of circadian rhythm and beta-blocker therapy over traditional time and frequency domain RR and QT variability indexes. RESULTS: The asymptomatic MCs differed significantly from the symptomatic MCs and from NMCs in less vagal control of heart rate and more reactive sympathetic modulation of the QT interval, particularly during daytime when arrhythmia risk for patients with LQT1 is greatest. CONCLUSIONS: The present data identified an additional factor contributing to the differential arrhythmic risk among patients with LQT1 carrying the same mutation. A healthy autonomic control confers a high risk, whereas patients with higher sympathetic control of the QT interval and reduced vagal control of heart rate are at lower risk. This differential "autonomic make-up," likely under genetic control, will allow refinement of risk stratification within families with LQTS, leading to more targeted management.
AU  - Porta, A.*
AU  - Girardengo, G.*
AU  - Bari, V.*
AU  - George, A.L. Jr.*
AU  - Brink, P.A.*
AU  - Goosen, A.*
AU  - Crotti, L.
AU  - Schwartz, P.J.*
C1  - 43192
C2  - 36310
CY  - New York
SP  - 367-374
TI  - Autonomic control of heart rate and QT interval variability influences arrhythmic risk in long QT syndrome type 1.
JO  - J. Am. Coll. Cardiol.
VL  - 65
IS  - 4
PB  - Elsevier Science Inc
PY  - 2015
SN  - 0735-1097
ER  - 

TY  - JOUR
AU  - Crotti, L.
AU  - Schwartz, P.J.*
C1  - 30661
C2  - 33781
CY  - New York
SP  - 1438–1440
TI  - Drug-induced long QT syndrome and exome sequencing: Chinese shadows link past and future.
JO  - J. Am. Coll. Cardiol.
VL  - 63
IS  - 14
PB  - Elsevier Science Inc
PY  - 2014
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - OBJECTIVES: To identify non-redundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk. BACKGROUND: AF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored. METHODS: We performed association testing conditioned on the most significant, independently associated genetic markers at nine established AF loci using two complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases). RESULTS: We observed at least four distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining eight AF loci. A multilocus score comprised of 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements. CONCLUSIONS: The chromosome 4q25 AF locus is architecturally complex and harbors at least four AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity.
AU  - Lubitz, S.A.*
AU  - Lunetta, K.L.*
AU  - Lin, H.*
AU  - Arking, D.E.*
AU  - Trompet, S.*
AU  - Li, G.*
AU  - Krijthe, B.P.*
AU  - Chasman, D.I.*
AU  - Barnard, J.*
AU  - Kleber, M.E.*
AU  - Dörr, M.*
AU  - Ozaki, K.*
AU  - Smith, A.V.*
AU  - Müller-Nurasyid, M.
AU  - Walter, S.*
AU  - Agarwal, S.K.*
AU  - Bis, J.C.*
AU  - Brody, J.A.*
AU  - Chen, L.Y.*
AU  - Everett, B.M.*
AU  - Ford, I.*
AU  - Franco, O.H.*
AU  - Harris, T.B.*
AU  - Hofman, A.*
AU  - Kääb, S.*
AU  - Mahida, S.*
AU  - Kathiresan, S.*
AU  - Kubo, M.*
AU  - Launer, L.J.*
AU  - Macfarlane, P.W.*
AU  - Magnani, J.W.*
AU  - McKnight, B.*
AU  - McManus, D.D.*
AU  - Peters, A.
AU  - Psaty, B.M.*
AU  - Rose, L.M.*
AU  - Rotter, J.I.*
AU  - Silbernagel, G.*
AU  - Smith, J.D.*
AU  - Sotoodehnia, N.*
AU  - Stott, D.J.*
AU  - Taylor, K.D.*
AU  - Tomaschitz, A.*
AU  - Tsunoda, T.*
AU  - Uitterlinden, A.G.*
AU  - van Wagoner, D.R.*
AU  - Völker, U.*
AU  - Völzke, H.*
AU  - Murabito, J.M.*
AU  - Sinner, M.F.*
AU  - Gudnason, V.*
AU  - Felix, S.B.*
AU  - Marz, W.*
AU  - Chung, M.*
AU  - Albert, C.M.*
AU  - Stricker, B.H.*
AU  - Tanaka, T.*
AU  - Heckbert, S.R.*
AU  - Jukema, J.W.*
AU  - Alonso, A.*
AU  - Benjamin, E.J.*
AU  - Ellinor, P.T.*
C1  - 29315
C2  - 33749
CY  - New York
SP  - 1200-1210
TI  - Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.
JO  - J. Am. Coll. Cardiol.
VL  - 63
IS  - 12
PB  - Elsevier Science Inc
PY  - 2014
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - OBJECTIVES: The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). BACKGROUND: Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective. METHODS: Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented. RESULTS: Patients (56% female, 27% symptomatic, heart rate 76 ± 16 beats/min, QTc 472 ± 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol. CONCLUSIONS: Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.
AU  - Chockalingam, P.*
AU  - Crotti, L.
AU  - Girardengo, G.*
AU  - Johnson, J.N.*
AU  - Harris, K.M.*
AU  - van der Heijden, J.F.*
AU  - Hauer, R.N.*
AU  - Beckmann, B.M.*
AU  - Spazzolini, C.*
AU  - Rordorf, R.*
AU  - Rydberg, A.*
AU  - Clur, S.A.*
AU  - Fischer, M.*
AU  - van den Heuvel, F.*
AU  - Kääb, S.*
AU  - Blom, N.A.*
AU  - Ackerman, M.J.*
AU  - Schwartz, P.J.*
AU  - Wilde, A.A.*
C1  - 26370
C2  - 32197
SP  - 2092-2099
TI  - Not all beta-blockers are equal in the management of long QT syndrome types 1 and 2: Higher recurrence of events under metoprolol.
JO  - J. Am. Coll. Cardiol.
VL  - 60
IS  - 20
PB  - Elsevier
PY  - 2012
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Objectives The aim of this study was to provide the spectrum and prevalence of mutations in the 12 Brugada syndrome (BrS)-susceptibility genes discovered to date in a single large cohort of unrelated BrS patients. Background BrS is a potentially lethal heritable arrhythmia syndrome diagnosed electrocardiographically by coved-type ST-segment elevation in the right precordial leads (V-1 to V-3; type 1 Brugada electrocardiographic [ECG] pattern) and the presence of a personal/family history of cardiac events. Methods Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing, comprehensive mutational analysis of BrS1-through BrS12-susceptibility genes was performed in 129 unrelated patients with possible/probable BrS (46 with clinically diagnosed BrS [ECG pattern plus personal/family history of a cardiac event] and 83 with a type 1 BrS ECG pattern only). Results Overall, 27 patients (21%) had a putative pathogenic mutation, absent in 1,400 Caucasian reference alleles, including 21 patients with an SCN5A mutation, 2 with a CACNB2B mutation, and 1 each with a KCNJ8 mutation, a KCND3 mutation, an SCN1Bb mutation, and an HCN4 mutation. The overall mutation yield was 23% in the type 1 BrS ECG pattern-only patients versus 17% in the clinically diagnosed BrS patients and was significantly greater among young men <20 years of age with clinically diagnosed BrS and among patients who had a prolonged PQ interval. Conclusions We identified putative pathogenic mutations in similar to 20% of our BrS cohort, with BrS genes 2 through 12 accounting for <5%. Importantly, the yield was similar between patients with only a type 1 BrS ECG pattern and those with clinically established BrS. The yield approaches 40% for SCN5A-mediated BrS (BrS1) when the PQ interval exceeds 200 ms. Calcium channel-mediated BrS is extremely unlikely in the absence of a short QT interval.
AU  - Crotti, L.
AU  - Marcou, C.A.*
AU  - Tester, D.J.*
AU  - Castelletti, S.*
AU  - Giudicessi, J.R.*
AU  - Torchio, M.*
AU  - Medeiros-Domingo, A.*
AU  - Simone, S.*
AU  - Will, M.L.*
AU  - Dagradi, F.*
AU  - Schwartz, P.J.*
AU  - Ackerman, M.J.*
C1  - 10700
C2  - 30397
SP  - 1410-1418
TI  - Spectrum and prevalence of mutations involving BrS1- through BrS12-susceptibility genes in a cohort of unrelated patients referred for Brugada Syndrome genetic testing: Implications for genetic testing.
JO  - J. Am. Coll. Cardiol.
VL  - 60
IS  - 15
PB  - Elsevier
PY  - 2012
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Objectives The study assessed whether heart rate (HR) reduction following an exercise stress test (ExStrT), an easily quantifiable marker of vagal reflexes, might identify high-and low-risk long QT syndrome (LQTS) type 1 (LQT1) patients. Background Identification of LQTS patients more likely to be symptomatic remains elusive. We have previously shown that depressed baroreflex sensitivity, an established marker of reduced vagal reflexes, predicts low probability of symptoms among LQT1. Methods We studied 169 LQTS genotype-positive patients < 50 years of age who performed an ExStrT with the same protocol, on and off beta-blockers including 47 South African LQT1 patients all harboring the KCNQ1-A341V mutation and 122 Italian LQTS patients with impaired (I-Ks-, 66 LQT1) or normal (I-Ks +/-, 50 LQT2 and 6 LQT3) I-Ks current. Results Despite similar maximal HR and workload, by the first minute after cessation of exercise the symptomatic patients in both IKs-groups had a greater HR reduction compared with the asymptomatic (19 +/- 7 beats/min vs. 13 +/- 5 beats/min and 27 +/- 10 beats/min vs. 20 +/- 8 beats/min, both p = 0.009). By contrast, there was no difference between the I-Ks +/- symptomatic and asymptomatic patients (23 +/- 9 beats/min vs. 26 +/- 9 beats/min, p = 0.47). LQT1 patients in the upper tertile for HR reduction had a higher risk of being symptomatic (odds ratio: 3.28, 95% confidence interval: 1.3 to 8.3, p = 0.012). Conclusions HR reduction following exercise identifies LQT1 patients at high or low arrhythmic risk, independently of beta-blocker therapy, and contributes to risk stratification. Intense exercise training, which potentiates vagal reflexes, should probably be avoided by LQT1 patients.
AU  - Crotti, L.
AU  - Spazzolini, C.*
AU  - Porretta, A.P.*
AU  - Dagradi, F.*
AU  - Taravelli, E.*
AU  - Petracci, B.*
AU  - Vicentini, A.*
AU  - Pedrazzini, M.*
AU  - La Rovere, M.T.*
AU  - Vanoli, E.*
AU  - Goosen, A.*
AU  - Heradien, M.*
AU  - George, A.L.*
AU  - Brink, P.A.*
AU  - Schwartz, P.J.*
C1  - 11635
C2  - 30736
SP  - 2515-2524
TI  - Vagal reflexes following an exercise stress test: A simple clinical tool for gene-specific risk stratification in the long QT syndrome.
JO  - J. Am. Coll. Cardiol.
VL  - 60
IS  - 24
PB  - Elsevier
PY  - 2012
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - OBJECTIVES: This study sought to develop a 2-dimensional (2D) intravascular near-infrared fluorescence (NIRF) imaging strategy for investigation of arterial inflammation in coronary-sized vessels.BACKGROUND: Molecular imaging of arterial inflammation could provide new insights into the pathogenesis of acute myocardial infarction stemming from coronary atheromata and implanted stents. Presently, few high-resolution approaches can image inflammation in coronary-sized arteries in vivo.METHODS:A new 2.9-F rotational, automated pullback 2D imaging catheter was engineered and optimized for 360° viewing intravascular NIRF imaging. In conjunction with the cysteine protease-activatable imaging reporter Prosense VM110 (VisEn Medical, Woburn, Massachusetts), intra-arterial 2D NIRF imaging was performed in rabbit aortas with atherosclerosis (n =10) or implanted coronary bare-metal stents (n = 10, 3.5-mm diameter, day 7 post-implantation). Intravascular ultrasound provided coregistered anatomical images of arteries. After sacrifice, specimens underwent ex vivo NIRF imaging, fluorescence microscopy, and histological and immunohistochemical analyses. RESULTS: Imaging of coronary artery-scaled phantoms demonstrated 8-sector angular resolution and submillimeter axial resolution, nanomolar sensitivity to NIR fluorochromes, and modest NIRF light attenuation through blood. High-resolution NIRF images of vessel wall inflammation with signal-to-noise ratios >10 were obtained in real-time through blood, without flushing or occlusion. In atherosclerosis, 2D NIRF, intravascular ultrasound-NIRF fusion, microscopy, and immunoblotting studies provided insight into the spatial distribution of plaque protease activity. In stent-implanted vessels, real-time imaging illuminated an edge-based pattern of stent-induced arterial inflammation. CONCLUSIONS: A new 2D intravascular NIRF imaging strategy provides high-resolution in vivo spatial mapping of arterial inflammation in coronary-sized arteries and reveals increased inflammation-regulated cysteine protease activity in atheromata and stent-induced arterial injury.
AU  - Jaffer, F.A.*
AU  - Calfon, M.A.*
AU  - Rosenthal, A.
AU  - Mallas, G.*
AU  - Razansky, R.N.
AU  - Mauskapf, A.*
AU  - Weissleder, R.*
AU  - Libby, P.*
AU  - Ntziachristos, V.
C1  - 4434
C2  - 28578
SP  - 2516-2526
TI  - Two-dimensional intravascular near-infrared fluorescence molecular imaging of inflammation in atherosclerosis and stent-induced vascular injury.
JO  - J. Am. Coll. Cardiol.
VL  - 57
IS  - 25
PB  - Elsevier
PY  - 2011
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455), and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with noncarriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in 19 case-control studies of nonfatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results A total of 17,000 cases and 39,369 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the 19 studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with noncarriers. Regression analyses and fixed-effects meta-analyses ruled out with high degree of confidence an increase of >= 2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early-onset disease (younger than 50 years of age for men and younger than 60 years of age for women) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study.
AU  - Assimes, T.L.*
AU  - Holm, H.*
AU  - Kathiresan, S.*
AU  - Reilly, M.P.*
AU  - Thorleifsson, G.*
AU  - Voight, B.F.*
AU  - Erdmann, J.*
AU  - Willenborg, C.*
AU  - Vaidya, D.*
AU  - Xie, C.C.*
AU  - Patterson, C.C.*
AU  - Morgan, T.M.*
AU  - Burnett, M.S.*
AU  - Li, M.Y*
AU  - Hlatky, M.A.*
AU  - Knowles, J.W.*
AU  - Thompson, J.R.*
AU  - Absher, D.*
AU  - Iribarren, C.*
AU  - Go, A.*
AU  - Fortmann, S.P.*
AU  - Sidney, S.*
AU  - Risch, N.*
AU  - Tang, H.*
AU  - Myers, R.M.*
AU  - Berger, K.*
AU  - Stoll, M.*
AU  - Shah, S.H.*
AU  - Thorgeirsson, G.*
AU  - Andersen, K.*
AU  - Havulinna, A.S.*
AU  - Herrera, J.E.*
AU  - Faraday, N.*
AU  - Kim, Y.*
AU  - Kral, B.G.*
AU  - Mathias, R.A.*
AU  - Ruczinski, I.*
AU  - Suktitipat, B.*
AU  - Wilson, A.F.*
AU  - Yanek, L.R.*
AU  - Becker, L.C.*
AU  - Linsel-Nitschke, P.*
AU  - Lieb, W.*
AU  - König, I.R.*
AU  - Hengstenberg, C.*
AU  - Fischer, M.*
AU  - Stark, K.*
AU  - Reinhard, W.*
AU  - Winogradow, J.*
AU  - Grassl, M.*
AU  - Grosshennig, A.*
AU  - Preuss, M.*
AU  - Schreiber, S.*
AU  - Wichmann, H.-E.
AU  - Meisinger, C.
AU  - Yee, J.*
AU  - Friedlander, Y.*
AU  - Do, R.*
AU  - Meigs, J.B.*
AU  - Williams, G.*
AU  - Nathan, D.M.*
AU  - MacRae, C.A.*
AU  - Qu, L.M.*
AU  - Wilensky, R.L.*
AU  - Matthai, W.H.*
AU  - Qasim, A.N.*
AU  - Hakonarson, H.*
AU  - Pichard, A.D.*
AU  - Kent, K.M.*
AU  - Satler, L.*
AU  - Lindsay, J.M.*
AU  - Waksman, R.*
AU  - Knouff, C.W.*
AU  - Waterworth, D.M.*
AU  - Walker, M.C.*
AU  - Mooser, V.E.*
AU  - Marrugat, J.*
AU  - Lucas, G.*
AU  - Subirana, I.*
AU  - Sala, J.*
AU  - Ramos, R.*
AU  - Martinelli, N.*
AU  - Olivieri, O.*
AU  - Trabetti, E.*
AU  - Malerba, G.*
AU  - Pignatti, P.F.*
AU  - Guiducci, C.*
AU  - Mirel, D.*
AU  - Parkin, M.*
AU  - Hirschhorn, J.N.*
AU  - Asselta, R.*
AU  - Duga, S.*
AU  - Musunuru, K.*
AU  - Daly, M.J.*
AU  - Purcell, S.*
AU  - Eifert, S.*
AU  - Braund, P.S.*
AU  - Wright, B.J.*
AU  - Balmforth, A.J.*
AU  - Ball, S.G.*
AU  - Ouwehand, W.H.*
AU  - Deloukas, P.*
AU  - Scholz, M.*
AU  - Cambien, F.*
AU  - Huge, A.*
AU  - Scheffold, T.*
AU  - Salomaa, V.*
AU  - Girelli, D.*
AU  - Granger, C.B.*
AU  - Peltonen, L.*
AU  - McKeown, P.P.*
AU  - Altshuler, D.*
AU  - Melander, O.*
AU  - Devaney, J.M.*
AU  - Epstein, S.E.*
AU  - Rader, D.J.*
AU  - Elosua, R.*
AU  - Engert, J.C.*
AU  - Anand, S.S.*
AU  - Hall, A.S.*
AU  - Ziegler, A.*
AU  - O'Donnell, C.J.*
AU  - Spertus, J.A.*
AU  - Siscovick, D.*
AU  - Schwartz, S.M.*
AU  - Becker, D.*
AU  - Thorsteinsdottir, U.*
AU  - Stefansson, K.*
AU  - Schunkert, H.*
AU  - Samani, N.J.*
AU  - Quertermous, T.*
C1  - 642
C2  - 27993
CY  - New York
SP  - 1552-1563
TI  - Lack of association between the Trp719Arg polymorphism in kinesin-like protein-6 and coronary artery disease in 19 case-control studies.
JO  - J. Am. Coll. Cardiol.
VL  - 56
IS  - 19
PB  - Elsevier Science Inc.
PY  - 2010
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - OBJECTIVES: We studied the relationship between changes in body composition and changes in blood pressure levels. BACKGROUND: The mechanisms underlying the frequently observed progression from pre-hypertension to hypertension are poorly understood. METHODS: We examined 1,145 subjects from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. First, we studied individuals pre-hypertensive at baseline who, during 10 years of follow-up, either had normalized blood pressure (PreNorm, n = 48), persistently had pre-hypertension (PrePre, n = 134), or showed progression to hypertension (PreHyp, n = 183). In parallel, we studied predictors for changes in blood pressure category in individuals hypertensive at baseline (n = 429). RESULTS: After 10 years, the PreHyp group was characterized by a marked increase in body weight (+5.71% [95% confidence interval (CI): 4.60% to 6.83%]) that was largely the result of an increase in fat mass (+17.8% [95% CI: 14.5% to 21.0%]). In the PrePre group, both the increases in body weight (+1.95% [95% CI: 0.68% to 3.22%]) and fat mass (+8.09% [95% CI: 4.42% to 11.7%]) were significantly less pronounced than in the PreHyp group (p < 0.001 for both). The PreNorm group showed no significant change in body weight (-1.55% [95% CI: -3.70% to 0.61%]) and fat mass (+0.20% [95% CI: -6.13% to 6.52%], p < 0.05 for both, vs. the PrePre group). CONCLUSIONS: After 10 years of follow-up, hypertension developed in 50.1% of individuals with pre-hypertension and only 6.76% went from hypertensive to pre-hypertensive blood pressure levels. An increase in body weight and fat mass was a risk factor for the development of sustained hypertension, whereas a decrease was predictive of a decrease in blood pressure.
AU  - Markus, M.R.P.*
AU  - Stritzke, J.*
AU  - Siewert, U.*
AU  - Lieb, W.*
AU  - Luchner, A.*
AU  - Döring, A.
AU  - Keil, U.*
AU  - Hense, H.W.*
AU  - Schunkert, H.*
C1  - 2716
C2  - 27552
SP  - 65-76
TI  - Variation in body composition determines long-term blood pressure changes in pre-hypertension: The MONICA/KORA (Monitoring Trends and Determinants on Cardiovascular Diseases/Cooperative Research in the Region of Augsburg) cohort study.
JO  - J. Am. Coll. Cardiol.
VL  - 56
IS  - 1
PB  - Elsevier
PY  - 2010
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - Pulmonary arterial hypertension (PAH) is a rare disorder that may be hereditable (HPAH), idiopathic (IPAH), or associated with either drug-toxin exposures or other medical conditions. Familial cases have long been recognized and are usually due to mutations in the bone morphogenetic protein receptor type 2 gene (BMPR2), or, much less commonly, 2 other members of the transforming growth factor-β superfamily, activin-like kinase-type 1 (ALK1) and endoglin (ENG), which are associated with hereditary hemorrhagic telangiectasia. In addition, approximately 20% of patients with IPAH carry mutations in BMPR2. We provide a summary of BMPR2 mutations associated with HPAH, most of which are unique to each family and are presumed to result in loss of function. We review the finding of missense variants and variants of unknown significance in BMPR2 in IPAH/HPAH, fenfluramine exposure, and PAH associated with congenital heart disease. Clinical testing for BMPR2 mutations is available and may be offered to HPAH and IPAH patients but should be preceded by genetic counseling, since lifetime penetrance is only 10% to 20%, and there are currently no known effective preventative measures. Identification of a familial mutation can be valuable in reproductive planning and identifying family members who are not mutation carriers and thus will not require lifelong surveillance. With advances in genomic technology and with international collaborative efforts, genome-wide association studies will be conducted to identify additional genes for HPAH, genetic modifiers for BMPR2 penetrance and genetic susceptibility to IPAH. In addition, collaborative studies of BMPR2 mutation carriers should enable identification of environmental modifiers, biomarkers for disease development and progression, and surrogate markers for efficacy end points in clinical drug development, thereby providing an invaluable resource for trials of PAH prevention.
AU  - Machado, R.D.*
AU  - Eickelberg, O.
AU  - Elliott, C.G.*
AU  - Geraci, M.W.*
AU  - Hanaoka, M.*
AU  - Loyd, J.E.*
AU  - Newman, J.H.*
AU  - Phillips, J.A.*
AU  - Soubrier, F.*
AU  - Trembath, R.C.*
AU  - Chung, W.K.*
C1  - 1114
C2  - 26752
CY  - New York
SP  - S32-S42
TI  - Genetics and genomics of pulmonary arterial hypertension.
JO  - J. Am. Coll. Cardiol.
VL  - 54
IS  - 1
PB  - Elsevier Science
PY  - 2009
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - This prospective study evaluated the association of obesity and hypertension with left atrial (LA) volume over 10 years. Background Although left atrial enlargement (LAE) is an independent risk factor for atrial fibrillation, stroke, and death, little information is available about determinants of LA size in the general population. Methods Participants (1,212 men and women, age 25 to 74 years) originated from a sex-and age-stratified random sample of German residents of the Augsburg area (MONICA S3). Left atrial volume was determined by standardized echocardiography at baseline and again after 10 years. Left atrial volume was indexed to body height (iLA). Left atrial enlargement was defined as iLA >= 35.7 and >= 33.7 ml/m in men and women, respectively. Results At baseline, the prevalence of LAE was 9.8%. Both obesity and hypertension were independent predictors of LAE, obesity (odds ratio [OR]: 2.4; p < 0.001) being numerically stronger than hypertension (OR: 2.2; p < 0.001). Adjusted mean values for iLA were significantly lower in normal-weight hypertensive patients (25.4 ml/m) than in obese normotensive individuals (27.3 ml/m; p = 0.016). The highest iLA was found in the obese hypertensive subgroup (30.0 ml/m; p < 0.001 vs. all other groups). This group also presented with the highest increase in iLA (+6.0 ml/m) and the highest incidence (31.6%) of LAE upon follow-up. Conclusions In the general population, obesity appears to be the most important risk factor for LAE. Given the increasing prevalence of obesity, early interventions, especially in young obese individuals, are essential to prevent premature onset of cardiac remodeling at the atrial level.
AU  - Stritzke, J.*
AU  - Markus, M.R.*
AU  - Duderstadt, S.*
AU  - Lieb, W.*
AU  - Luchner, A.*
AU  - Döring, A.
AU  - Keil, U.*
AU  - Hense, H.W.*
AU  - Schunkert, H.*
C1  - 1251
C2  - 26493
CY  - New York
SP  - 1982-1989
TI  - The aging process of the heart: Obesity is the main risk factor for left atrial enlargement during aging the MONICA/KORA (monitoring of trends and determinations in cardiovascular disease/cooperative research in the region of Augsburg) study.
JO  - J. Am. Coll. Cardiol.
VL  - 54
IS  - 21
PB  - Elsevier Science Inc
PY  - 2009
SN  - 0735-1097
ER  - 

TY  - JOUR
AB  - This study was designed to investigate whether single nucleotide polymorphisms (SNPs) and haplotypes of the fibrinogen gene-cluster (fibrinogen chains alpha [FGA], beta [FGB], and gamma [FGG]) could explain the inter- and intraindividual variability of fibrinogen levels in patients with atherosclerosis. We also searched for genetic determinants affecting the responses of fibrinogen genes to proinflammatory stimulation. BACKGROUND: The mechanisms regulating fibrinogen levels are not fully understood, and they are likely to be regulated by complex gene-environment interactions. METHODS: In the AIRGENE study, 895 survivors of myocardial infarction from 5 European cities were followed prospectively for 6 to 8 months, and plasma fibrinogen, interleukin (IL)-6, and C-reactive protein levels were determined monthly. We analyzed 21 SNPs and the corresponding haplotypes in the 3 fibrinogen genes. RESULTS: Eight SNPs in FGA and FGB were significantly associated with fibrinogen levels. Similarly, 2 different haplotypes in FGA and 3 in FGB were also associated with mean fibrinogen levels. The IL-6 levels had a significant impact on the associations between SNPs/haplotypes in FGA/FGB and fibrinogen levels. We also identified SNPs and haplotypes in FGA and FGB with strong impact on the intraindividual variability of fibrinogen during the follow-up period. CONCLUSIONS: We identified common SNPs and haplotypes on FGA/FGB genes, explaining the interindividual and intraindividual variability of fibrinogen levels, in patients with a history of myocardial infarction. We have also identified for the first time, SNPs/haplotypes on FGA/FGB whose effects on fibrinogen expression are modified by the underlying IL-6 levels. These findings may have an impact on risk stratification and the design of genetically guided therapeutic approaches in patients with advanced atherosclerosis.
AU  - Jacquemin, B.*
AU  - Antoniades, C.*
AU  - Nyberg, F.*
AU  - Plana, E.*
AU  - Müller, M.
AU  - Greven, S.
AU  - Salomaa, V.*
AU  - Sunyer, J.*
AU  - Bellander, T.*
AU  - Chalamandaris, A.G.*
AU  - Pistelli, R.*
AU  - Koenig, W.*
AU  - Peters, A.
C1  - 4773
C2  - 25733
SP  - 941-952
TI  - Common genetic polymorphisms and haplotypes of fibrinogen alpha, beta, and gamma chains affect fibrinogen levels and the response to proinflammatory stimulation in myocardial infarction survivors: The AIRGENE study.
JO  - J. Am. Coll. Cardiol.
VL  - 52
IS  - 11
PB  - Elsevier
PY  - 2008
SN  - 0735-1097
ER  - 

TY  - JOUR
AU  - Koenig, W.*
AU  - Khuseyinova, N.*
AU  - Baumert, J.J.
AU  - Meisinger, C.
AU  - Löwel, H.
C1  - 3867
C2  - 24055
SP  - 1369-1377
TI  - Serum concentrations of adiponectin and risk of type 2 diabetes mellitus and coronary heart disease in apparently healthy middle-aged men: Results from the 18-year follow-up of large cohort from Southern Germany.
JO  - J. Am. Coll. Cardiol.
VL  - 48
PY  - 2006
SN  - 0735-1097
ER  - 

TY  - JOUR
AU  - Schunkert, H.*
AU  - Döring, A.
AU  - Riegger, G.A.*
AU  - Hense, H.W.*
C1  - 20910
C2  - 18955
SP  - 1685-1691
TI  - Familial Predisposition of Left Ventricular Hypertrophy.
JO  - J. Am. Coll. Cardiol.
VL  - 33
PY  - 1999
SN  - 0735-1097
ER  -