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Article ; Online: Longitudinal Hemodynamic Correlates of and Sex Differences in the Evolution of Blood Pressure Across the Adult Lifespan: The Framingham Heart Study.

Mitchell, Gary F / Rong, Jian / Larson, Martin G / Cooper, Leroy L / Xanthakis, Vanessa / Benjamin, Emelia J / Hamburg, Naomi M / Vasan, Ramachandran S

Journal of the American Heart Association

2023 Volume 12, Issue 12, Page(s) e027329

Abstract: Background Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle-aged and older adults. Relative contributions of aortic stiffness and premature wave ... ...

Abstract	Background Systolic blood pressure increases with age after midlife, particularly in women, and contributes to development of wide pulse pressure hypertension in middle-aged and older adults. Relative contributions of aortic stiffness and premature wave reflection to increases in pulse pressure remain controversial. Methods and Results We evaluated visit-specific values and change in key correlates of pulse pressure, aortic characteristic impedance, forward and backward wave amplitude, and global reflection coefficient, at 3 sequential examinations of the Framingham Generation 3 (N=4082), Omni-2 (N=410), and New Offspring Spouse (N=103) cohorts (53% women). Data were analyzed using repeated-measures linear mixed models adjusted for age, sex, and risk factor exposures. Pulse pressure increased markedly with age after midlife (age and age-squared terms,
MeSH term(s)	Middle Aged ; Female ; Humans ; Male ; Aged ; Blood Pressure/physiology ; Longevity ; Sex Characteristics ; Hemodynamics/physiology ; Hypertension/diagnosis ; Hypertension/epidemiology ; Longitudinal Studies ; Vascular Stiffness/physiology ; Pulse Wave Analysis/methods
Language	English
Publishing date	2023-06-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.122.027329
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Article ; Online: Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

Wang, Xuzhi / Zhang, Yuankai / Pathiravasan, Chathurangi H / Ukonu, Nene C / Rong, Jian / Benjamin, Emelia J / McManus, David D / Larson, Martin G / Vasan, Ramachandran S / Hamburg, Naomi M / Murabito, Joanne M / Liu, Chunyu / Mitchell, Gary F

JMIR cardio

2024 Volume 8, Page(s) e54801

Abstract: Background: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, ... ...

Abstract	Background: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. Objective: This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. Methods: At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. Results: Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). Conclusions: In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.
Language	English
Publishing date	2024-04-08
Publishing country	Canada
Document type	Journal Article
ISSN	2561-1011
ISSN (online)	2561-1011
DOI	10.2196/54801
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Article ; Online: Arteriosclerosis, Atherosclerosis, and Cardiovascular Health: Joint Relations to the Incidence of Cardiovascular Disease.

Vasan, Ramachandran S / Pan, Stephanie / Larson, Martin G / Mitchell, Gary F / Xanthakis, Vanessa

Hypertension (Dallas, Tex. : 1979)

2021 Volume 78, Issue 5, Page(s) 1232–1240

Abstract: Figure: see text]. ...

Abstract	[Figure: see text].
MeSH term(s)	Adult ; Aged ; Arteriosclerosis/diagnosis ; Arteriosclerosis/epidemiology ; Arteriosclerosis/physiopathology ; Atherosclerosis/diagnosis ; Atherosclerosis/epidemiology ; Atherosclerosis/physiopathology ; Blood Flow Velocity ; Cardiovascular Diseases/diagnosis ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/physiopathology ; Carotid Arteries/physiopathology ; Cohort Studies ; Female ; Humans ; Hypertension/diagnosis ; Hypertension/epidemiology ; Hypertension/physiopathology ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Pulse Wave Analysis/methods ; United States/epidemiology ; Vascular Stiffness/physiology
Language	English
Publishing date	2021-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	423736-5
ISSN	1524-4563 ; 0194-911X ; 0362-4323
ISSN (online)	1524-4563
ISSN	0194-911X ; 0362-4323
DOI	10.1161/HYPERTENSIONAHA.121.18075
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Article ; Online: Prognosis of "pre-heart failure" clinical phenotypes.

Velagaleti, Raghava S / Short, Meghan I / Larson, Martin G / Vasan, Ramachandran S

PloS one

2020 Volume 15, Issue 4, Page(s) e0231254

Abstract: Background: Heart failure (HF) is a clinical syndrome where diagnostic certainty varies. The prognosis of individuals with some clinical features of HF, but without the fully overt syndrome, is unclear. Therefore, we sought to evaluate their natural ... ...

Abstract	Background: Heart failure (HF) is a clinical syndrome where diagnostic certainty varies. The prognosis of individuals with some clinical features of HF, but without the fully overt syndrome, is unclear. Therefore, we sought to evaluate their natural history. Methods and results: Between 1990 and 2009, all suspected HF cases in the Framingham Heart Study were adjudicated into 3 groups reflecting varying diagnostic certainty: definite (meeting HF diagnostic criteria; n = 479), possible (meeting HF criteria but with an alternative explanation for findings; n = 135), and probable (insufficient criteria for definite HF; n = 121) HF. Age-and-sex-matched individuals (n = 1112) without HF or cardiovascular disease (CVD) were controls. Using multivariable-adjusted Cox regression, we compared the possible/probable HF groups with controls regarding risk of incident definite HF, coronary heart disease (CHD), other CVD or death; and with definite HF regarding risk of latter three outcomes. During follow-up (mean 8.6 years), ~90% of individuals with possible, probable and definite HF experienced CVD events or died. Compared with controls, those with possible or probable HF experienced higher hazards for definite HF, CHD, other CVD and death (hazards ratios [HR] 1.35-9.31; p<0.05). The possible/probable groups did not differ from the definite HF group for risk of any outcome. Compared with the possible HF group, the probable HF group had a higher propensity for definite HF (HR 1.64, with a higher proportion of ischemic HF) but lower risk of death (HR 0.69). Conclusions: Individuals meeting partial criteria for HF are at a substantial risk for progression to HF, CVD, and mortality.
MeSH term(s)	Aged ; Case-Control Studies ; Female ; Follow-Up Studies ; Heart Failure/diagnosis ; Heart Failure/epidemiology ; Heart Failure/pathology ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Phenotype ; Prognosis ; Risk Factors ; Uncertainty
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0231254
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Article ; Online: A comparison of statistical methods to predict the residual lifetime risk.

Conner, Sarah C / Beiser, Alexa / Benjamin, Emelia J / LaValley, Michael P / Larson, Martin G / Trinquart, Ludovic

European journal of epidemiology

2022 Volume 37, Issue 2, Page(s) 173–194

Abstract: Lifetime risk measures the cumulative risk for developing a disease over one's lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict ... ...

Abstract	Lifetime risk measures the cumulative risk for developing a disease over one's lifespan. Modeling the lifetime risk must account for left truncation, the competing risk of death, and inference at a fixed age. In addition, statistical methods to predict the lifetime risk should account for covariate-outcome associations that change with age. In this paper, we review and compare statistical methods to predict the lifetime risk. We first consider a generalized linear model for the lifetime risk using pseudo-observations of the Aalen-Johansen estimator at a fixed age, allowing for left truncation. We also consider modeling the subdistribution hazard with Fine-Gray and Royston-Parmar flexible parametric models in left truncated data with time-covariate interactions, and using these models to predict lifetime risk. In simulation studies, we found the pseudo-observation approach had the least bias, particularly in settings with crossing or converging cumulative incidence curves. We illustrate our method by modeling the lifetime risk of atrial fibrillation in the Framingham Heart Study. We provide technical guidance to replicate all analyses in R.
MeSH term(s)	Atrial Fibrillation/epidemiology ; Bias ; Computer Simulation ; Humans ; Incidence ; Models, Statistical ; Proportional Hazards Models ; Survival Analysis
Language	English
Publishing date	2022-01-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	632614-6
ISSN	1573-7284 ; 0393-2990
ISSN (online)	1573-7284
ISSN	0393-2990
DOI	10.1007/s10654-021-00815-8
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Article ; Online: Glycoproteomic and Phenotypic Elucidation of

Stenfelt, Linn / Nilsson, Jonas / Hellberg, Åsa / Liew, Yew Wah / Morrison, Jenny / Larson, Göran / Olsson, Martin L

International journal of molecular sciences

2022 Volume 23, Issue 7

Abstract: ... A>G and rs61743617:C>T, found in a Sd(a−) compound heterozygote, gave results similar to wildtype ...

Abstract	The Sda histo-blood group antigen (GalNAcβ1-4(NeuAcα2-3)Galβ-R) is implicated in various infections and constitutes a potential biomarker for colon cancer. Sd(a−) individuals (2−4% of Europeans) may produce anti-Sda, which can lead to incompatible blood transfusions, especially if donors with the high-expressing Sd(a++)/Cad phenotype are involved. We previously reported the association of B4GALNT2 mutations with Sd(a−), which established the SID blood-group system. The present study provides causal proof underpinning this correlation. Sd(a−) HEK293 cells were transfected with different B4GALNT2 constructs and evaluated by immunostaining and glycoproteomics. The predominant SIDnull candidate allele with rs7224888:T>C (p.Cys406Arg) abolished Sda synthesis, while this antigen was detectable as N- or O-glycans on glycoproteins following transfection of wildtype B4GALNT2. Surprisingly, two rare missense variants, rs148441237:A>G and rs61743617:C>T, found in a Sd(a−) compound heterozygote, gave results similar to wildtype. To elucidate on whether Sd(a++)/Cad also depends on B4GALNT2 alterations, this gene was sequenced in five individuals. No Cad-specific changes were identified, but a detailed erythroid Cad glycoprotein profile was obtained, especially for glycophorin-A (GLPA) O-glycosylation, equilibrative nucleoside transporter 1 (S29A1) O-glycosylation, and band 3 anion transport protein (B3AT) N-glycosylation. In conclusion, the p.Cys406Arg β4GalNAc-T2 variant causes Sda-deficiency in humans, while the enigmatic Cad phenotype remains unresolved, albeit further characterized.
MeSH term(s)	Blood Group Antigens/genetics ; HEK293 Cells ; Humans ; N-Acetylgalactosaminyltransferases/genetics ; N-Acetylgalactosaminyltransferases/metabolism ; Phenotype
Chemical Substances	Blood Group Antigens ; N-Acetylgalactosaminyltransferases (EC 2.4.1.-) ; beta-1,4-N-acetyl-galactosaminyl transferase 2 (EC 2.4.1.165)
Language	English
Publishing date	2022-04-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23073936
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Article ; Online: Sex-specific differences in the genetic and environmental effects on cardiac phenotypic variation assessed by echocardiography.

Lin, Honghuang / Kwan, Alan C / Castro-Diehl, Cecilia / Short, Meghan I / Xanthakis, Vanessa / Yola, Ibrahim M / Salto, Gerran / Mitchell, Gary F / Larson, Martin G / Vasan, Ramachandran S / Cheng, Susan

Scientific reports

2023 Volume 13, Issue 1, Page(s) 5786

Abstract: The drivers of sexual dimorphism in heart failure phenotypes are currently poorly understood. Divergent phenotypes may result from differences in heritability and genetic versus environmental influences on the interplay of cardiac structure and function. ...

Abstract	The drivers of sexual dimorphism in heart failure phenotypes are currently poorly understood. Divergent phenotypes may result from differences in heritability and genetic versus environmental influences on the interplay of cardiac structure and function. To assess sex-specific heritability and genetic versus environmental contributions to variation and inter-relations between echocardiography traits in a large community-based cohort. We studied Framingham Heart Study participants of Offspring Cohort examination 8 (2005-2008) and Third Generation Cohort examination 1 (2002-2005). Five cardiac traits and six functional traits were measured using standardized echocardiography. Sequential Oligogenic Linkage Analysis Routines (SOLAR) software was used to perform singular and bivariate quantitative trait linkage analysis. In our study of 5674 participants (age 49 ± 15 years; 54% women), heritability for all traits was significant for both men and women. There were no significant differences in traits between men and women. Within inter-trait correlations, there were two genetic, and four environmental trait pairs with sex-based differences. Within both significant genetic trait pairs, men had a positive relation, and women had no significant relation. We observed significant sex-based differences in inter-trait genetic and environmental correlations between cardiac structure and function. These findings highlight potential pathways of sex-based divergent heart failure phenotypes.
MeSH term(s)	Male ; Female ; Humans ; Quantitative Trait, Heritable ; Sex Characteristics ; Phenotype ; Biological Variation, Population ; Echocardiography ; Heart Failure/diagnostic imaging ; Heart Failure/genetics ; Genetic Variation
Language	English
Publishing date	2023-04-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-32577-6
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Article: Association of Healthy Dietary Patterns and Cardiorespiratory Fitness in the Community.

Mi, Michael Y / Gajjar, Priya / Walker, Maura E / Miller, Patricia / Xanthakis, Vanessa / Murthy, Venkatesh L / Larson, Martin G / Vasan, Ramachandran S / Shah, Ravi V / Lewis, Gregory D / Nayor, Matthew

medRxiv : the preprint server for health sciences

2023

Abstract: Aims: To evaluate the associations of dietary indices and quantitative CRF measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology.: Methods: Framingham Heart Study (FHS) participants underwent ... ...

Abstract	Aims: To evaluate the associations of dietary indices and quantitative CRF measures in a large, community-based sample harnessing metabolomic profiling to interrogate shared biology. Methods: Framingham Heart Study (FHS) participants underwent maximum effort cardiopulmonary exercise tests for CRF quantification (via peak VO Results: In 2380 FHS participants (54±9 years, 54% female, BMI 28±5 kg/m Conclusion: Higher diet quality is associated with greater CRF cross-sectionally in a middle-aged community-dwelling sample, and metabolites highlight potential shared favorable effects on health.
Language	English
Publishing date	2023-02-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.09.23285714
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Article ; Online: Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.

Nayor, Matthew / Gajjar, Priya / Miller, Patricia / Murthy, Venkatesh L / Shah, Ravi V / Houstis, Nicholas E / Velagaleti, Raghava S / Larson, Martin G / Vasan, Ramachandran S / Lewis, Gregory D / Mitchell, Gary F

Journal of the American Heart Association

2023 Volume 12, Issue 21, Page(s) e029619

Abstract: Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community- ... ...

Abstract	Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Vascular Stiffness/physiology ; Cardiorespiratory Fitness ; Pulse Wave Analysis ; Obesity ; Oxygen
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2023-10-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.029619
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Article ; Online: Analysis of variance.

Larson, Martin G

Circulation

2008 Volume 117, Issue 1, Page(s) 115–121

MeSH term(s)	Analysis of Variance ; Models, Statistical ; Research ; Terminology as Topic
Language	English
Publishing date	2008-01-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.107.654335
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