@article {1396, title = {Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {96}, year = {2012}, month = {2012 Aug}, pages = {269-74}, abstract = {

BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF).

OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF.

DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged >=65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression.

RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95\% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95\% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535).

CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

}, keywords = {Aged, Alcohol Drinking, alpha-Linolenic Acid, Biomarkers, Body Mass Index, Cardiovascular Diseases, Diet, Fatty Acid Desaturases, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1938-3207}, doi = {10.3945/ajcn.112.037960}, author = {Lemaitre, Rozenn N and Sitlani, Colleen and Song, Xiaoling and King, Irena B and McKnight, Barbara and Spiegelman, Donna and Sacks, Frank M and Djouss{\'e}, Luc and Rimm, Eric B and Siscovick, David S and Mozaffarian, Dariush} } @article {6030, title = {The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium as a model of collaborative science.}, journal = {Epidemiology}, volume = {24}, year = {2013}, month = {2013 May}, pages = {346-8}, keywords = {Aging, Cohort Studies, Cooperative Behavior, Genome-Wide Association Study, Heart Failure, Humans, Incidence, Multicenter Studies as Topic, Myocardial Infarction, Research Support as Topic, Stroke, United States}, issn = {1531-5487}, doi = {10.1097/EDE.0b013e31828b2cbb}, author = {Psaty, Bruce M and Sitlani, Colleen} } @article {6562, title = {Plasma phospholipid and dietary α-linolenic acid, mortality, CHD and stroke: the Cardiovascular Health Study.}, journal = {Br J Nutr}, volume = {112}, year = {2014}, month = {2014 Oct 14}, pages = {1206-13}, abstract = {

Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18~:~3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged >=~65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0{\textperiodcentered}73 (95~\% CI 0{\textperiodcentered}61, 0{\textperiodcentered}88) and 0{\textperiodcentered}64 (95~\% CI 0{\textperiodcentered}52, 0{\textperiodcentered}80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.

}, keywords = {Aged, alpha-Linolenic Acid, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Diet, Female, Humans, Male, Mortality, Phospholipids, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, United States}, issn = {1475-2662}, doi = {10.1017/S0007114514001925}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and Sitlani, Colleen and Psaty, Bruce M and Rimm, Eric B and Song, Xiaoling and McKnight, Barbara and Spiegelman, Donna and King, Irena B and Lemaitre, Rozenn N} } @article {6397, title = {Plasma phospholipid saturated fatty acids and incident atrial fibrillation: the Cardiovascular Health Study.}, journal = {J Am Heart Assoc}, volume = {3}, year = {2014}, month = {2014 Jun 26}, pages = {e000889}, abstract = {

BACKGROUND: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF.

METHODS AND RESULTS: The study population included 2899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long-chain saturated fatty acids-palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)-with incident AF. During a median of 11.2 years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95\% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95\% CI) for AF in the top and bottom quartiles were 0.76 (95\% CI: 0.61, 0.95) for 18:0; 0.78 (95\% CI: 0.63, 0.97) for 20:0; 0.62 (95\% CI: 0.50, 0.78) for 22:0; and 0.68 (95\% CI: 0.55, 0.85) for 24:0.

CONCLUSIONS: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Eicosanoic Acids, Fatty Acids, Female, Humans, Longitudinal Studies, Male, Palmitic Acid, Phospholipids, Proportional Hazards Models, Prospective Studies, Risk Factors, Stearic Acids, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.114.000889}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and Djouss{\'e}, Luc and Heckbert, Susan R and King, Irena B and McKnight, Barbara and Sitlani, Colleen and Sacks, Frank M and Song, Xiaoling and Sotoodehnia, Nona and Spiegelman, Donna and Wallace, Erin R and Lemaitre, Rozenn N} } @article {6875, title = {Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0140496}, abstract = {

BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.

METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).

RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0{\texttimes}10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction >= 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.

}, keywords = {African Americans, Aged, Antihypertensive Agents, Cardiovascular Diseases, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Hypertension, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Treatment Outcome}, issn = {1932-6203}, doi = {10.1371/journal.pone.0140496}, author = {Bis, Joshua C and Sitlani, Colleen and Irvin, Ryan and Avery, Christy L and Smith, Albert Vernon and Sun, Fangui and Evans, Daniel S and Musani, Solomon K and Li, Xiaohui and Trompet, Stella and Krijthe, Bouwe P and Harris, Tamara B and Quibrera, P Miguel and Brody, Jennifer A and Demissie, Serkalem and Davis, Barry R and Wiggins, Kerri L and Tranah, Gregory J and Lange, Leslie A and Sotoodehnia, Nona and Stott, David J and Franco, Oscar H and Launer, Lenore J and St{\"u}rmer, Til and Taylor, Kent D and Cupples, L Adrienne and Eckfeldt, John H and Smith, Nicholas L and Liu, Yongmei and Wilson, James G and Heckbert, Susan R and Buckley, Brendan M and Ikram, M Arfan and Boerwinkle, Eric and Chen, Yii-Der Ida and de Craen, Anton J M and Uitterlinden, Andr{\'e} G and Rotter, Jerome I and Ford, Ian and Hofman, Albert and Sattar, Naveed and Slagboom, P Eline and Westendorp, Rudi G J and Gudnason, Vilmundur and Vasan, Ramachandran S and Lumley, Thomas and Cummings, Steven R and Taylor, Herman A and Post, Wendy and Jukema, J Wouter and Stricker, Bruno H and Whitsel, Eric A and Psaty, Bruce M and Arnett, Donna} } @article {6929, title = {Associations of Plasma Phospholipid SFAs with Total and Cause-Specific Mortality in Older Adults Differ According to SFA Chain Length.}, journal = {J Nutr}, volume = {146}, year = {2016}, month = {2016 Feb}, pages = {298-305}, abstract = {

BACKGROUND: Not much is known about the relations of circulating saturated fatty acids (SFAs), which are influenced by both metabolic and dietary determinants, with total and cause-specific mortality.

OBJECTIVE: We examined the associations of plasma phospholipid SFAs with total and cause-specific mortality among 3941 older adults from the Cardiovascular Health Study, a population-based prospective study of adults aged >=65 y who were followed from 1992 through 2011.

METHODS: The relations of total and cause-specific mortality with plasma phospholipid palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) were assessed using Cox proportional hazards models.

RESULTS: During 45,450 person-years of follow-up, 3134 deaths occurred. Higher concentrations of the plasma phospholipid SFAs 18:0, 22:0, and 24:0 were associated with a lower risk of total mortality [multivariable-adjusted HRs (95\% CIs)] for the top compared with the bottom quintile: 0.85 (0.75, 0.95) for 18:0; 0.85 (0.75, 0.95) for 22:0; and 0.80 (0.71, 0.90) for 24:0. In contrast, plasma 16:0 concentrations in the highest quintile were associated with a higher risk of total mortality compared with concentrations in the lowest quintile [1.25 (1.11, 1.41)]. We also found no association of plasma phospholipid 20:0 with total mortality.

CONCLUSIONS: These findings suggest that the associations of plasma phospholipid SFAs with the risk of death differ according to SFA chain length and support future studies to better characterize the determinants of circulating SFAs and to explore the mechanisms underlying these relations.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Diet, Dietary Fats, Eicosanoic Acids, Fatty Acids, Female, Humans, Male, Mortality, Palmitic Acid, Phospholipids, Prospective Studies, Risk Factors, Stearic Acids}, issn = {1541-6100}, doi = {10.3945/jn.115.222117}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and King, Irena B and McKnight, Barbara and Psaty, Bruce M and Rimm, Eric B and Sitlani, Colleen and Sacks, Frank M and Song, Xiaoling and Sotoodehnia, Nona and Spiegelman, Donna and Lemaitre, Rozenn N} } @article {9544, title = {A Type 1 Diabetes Polygenic Score Is Not Associated With Prevalent Type 2 Diabetes in Large Population Studies.}, journal = {J Endocr Soc}, volume = {7}, year = {2023}, month = {2023 Oct 09}, pages = {bvad123}, abstract = {

CONTEXT: Both type 1 diabetes (T1D) and type 2 diabetes (T2D) have significant genetic contributions to risk and understanding their overlap can offer clinical insight.

OBJECTIVE: We examined whether a T1D polygenic score (PS) was associated with a diagnosis of T2D in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.

METHODS: We constructed a T1D PS using 79 known single nucleotide polymorphisms associated with T1D risk. We analyzed 13 792 T2D cases and 14 169 controls from CHARGE cohorts to determine the association between the T1D PS and T2D prevalence. We validated findings in an independent sample of 2256 T2D cases and 27 052 controls from the Mass General Brigham Biobank (MGB Biobank). As secondary analyses in 5228 T2D cases from CHARGE, we used multivariable regression models to assess the association of the T1D PS with clinical outcomes associated with T1D.

RESULTS: The T1D PS was not associated with T2D both in CHARGE ( = .15) and in the MGB Biobank ( = .87). The partitioned human leukocyte antigens only PS was associated with T2D in CHARGE (OR 1.02 per 1 SD increase in PS, 95\% CI 1.01-1.03, = .006) but not in the MGB Biobank. The T1D PS was weakly associated with insulin use (OR 1.007, 95\% CI 1.001-1.012, = .03) in CHARGE T2D cases but not with other outcomes.

CONCLUSION: In large biobank samples, a common variant PS for T1D was not consistently associated with prevalent T2D. However, possible heterogeneity in T2D cannot be ruled out and future studies are needed do subphenotyping.

}, issn = {2472-1972}, doi = {10.1210/jendso/bvad123}, author = {Srinivasan, Shylaja and Wu, Peitao and Mercader, Josep M and Udler, Miriam S and Porneala, Bianca C and Bartz, Traci M and Floyd, James S and Sitlani, Colleen and Guo, Xiquing and Haessler, Jeffrey and Kooperberg, Charles and Liu, Jun and Ahmad, Shahzad and van Duijn, Cornelia and Liu, Ching-Ti and Goodarzi, Mark O and Florez, Jose C and Meigs, James B and Rotter, Jerome I and Rich, Stephen S and Dupuis, Jos{\'e}e and Leong, Aaron} } @article {9790, title = {A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.}, journal = {Res Sq}, year = {2024}, month = {2024 Jul 17}, abstract = {

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes{\textquoteright} functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

}, issn = {2693-5015}, doi = {10.21203/rs.3.rs-4163414/v1}, author = {Wang, Heming and Nagarajan, Pavithra and Winkler, Thomas and Bentley, Amy and Miller, Clint and Kraja, Aldi and Schwander, Karen and Lee, Songmi and Wang, Wenyi and Brown, Michael and Morrison, John and Giri, Ayush and O{\textquoteright}Connell, Jeffrey and Bartz, Traci and de Las Fuentes, Lisa and Gudmundsdottir, Valborg and Guo, Xiuqing and Harris, Sarah and Huang, Zhijie and Kals, Mart and Kho, Minjung and Lefevre, Christophe and Luan, Jian{\textquoteright}an and Lyytik{\"a}inen, Leo-Pekka and Mangino, Massimo and Milaneschi, Y and Palmer, Nicholette and Rao, Varun and Rauramaa, Rainer and Shen, Botong and Stadler, Stefan and Sun, Quan and Tang, Jingxian and Th{\'e}riault, S{\'e}bastien and van der Graaf, Adriaan and van der Most, Peter and Wang, Yujie and Weiss, Stefan and Westerman, Kenneth and Yang, Qian and Yasuharu, Tabara and Zhao, Wei and Zhu, Wanying and Altschul, Drew and Ansari, Md Abu Yusuf and Anugu, Pramod and Argoty-Pantoja, Anna and Arzt, Michael and Aschard, Hugues and Attia, John and Bazzano, Lydia and Breyer, Max and Brody, Jennifer and Cade, Brian and Chen, Hung-Hsin and Chen, Yii-Der Ida and Chen, Zekai and de Vries, Paul and Dimitrov, Latchezar and Do, Ahn and Du, Jiawen and Dupont, Charles and Edwards, Todd and Evans, Michele and Faquih, Tariq and Felix, Stephan and Fisher-Hoch, Susan and Floyd, James and Graff, Mariaelisa and Charles Gu, C and Gu, Dongfeng and Hairston, Kristen and Hanley, Anthony and Heid, Iris and Heikkinen, Sami and Highland, Heather and Hood, Michelle and K{\"a}h{\"o}nen, Mika and Karvonen-Gutierrez, Carrie and Kawaguchi, Takahisa and Kazuya, Setoh and Tanika, Kelly and Komulainen, Pirjo and Levy, Daniel and Lin, Henry and Liu, Peter and Marques-Vidal, Pedro and McCormick, Joseph and Mei, Hao and Meigs, James and Menni, Cristina and Nam, Kisung and Nolte, Ilja and Pacheco, Natasha and Petty, Lauren and Polikowsky, Hannah and Province, Michael and Psaty, Bruce and Raffield, Laura and Raitakari, Olli and Rich, Stephen and Riha, Renata and Risch, Lorenz and Risch, Martin and Ruiz-Narvaez, Edward and Scott, Rodney and Sitlani, Colleen and Smith, Jennifer and Sofer, Tamar and Teder-Laving, Maris and V{\"o}lker, Uwe and Vollenweider, Peter and Wang, Guanchao and van Dijk, Ko Willems and Wilson, Otis and Xia, Rui and Yao, Jie and Young, Kristin and Zhang, Ruiyuan and Zhu, Xiaofeng and Below, Jennifer and B{\"o}ger, Carsten and Conen, David and Cox, Simon and D{\"o}rr, Marcus and Feitosa, Mary and Fox, Ervin and Franceschini, Nora and Gharib, Sina and Gudnason, Vilmundur and Harlow, Sioban and He, Jiang and Holliday, Elizabeth and Kutalik, Zolt{\'a}n and Lakka, Timo and Lawlor, Deborah and Lee, Seunggeun and Lehtim{\"a}ki, Terho and Li, Changwei and Liu, Ching-Ti and M{\"a}gi, Reedik and Matsuda, Fumihiko and Morrison, Alanna and Penninx, Brenda W J H and Peyser, Patricia and Rotter, Jerome and Snieder, Harold and Spector, T and Wagenknecht, Lynne and Wareham, Nicholas and Zonderman, Alan and North, Kari and Fornage, Myriam and Hung, Adriana and Manning, Alisa and Gauderman, W and Chen, Han and Munroe, Patricia and Rao, Dabeeru and van Heemst, Diana and Redline, Susan and Noordam, Raymond} }