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Dilated hypertrophic phenotype of the carotid artery is associated with accelerated age-associated central arterial stiffening

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Abstract

Hypertrophic carotid geometric phenotypes (h-CGP) are predictors of incident cardiovascular disease (CVD). While arterial aging is hypothesized as a contributor to this associated risk, the association of CGPs with chronological age is not clear. In this manuscript we examine whether hypertrophic CGPs represent accelerated biological, rather than chronological, aging by examining their association with carotid-femoral pulse wave velocity (PWV), the hallmark of arterial aging. We analyzed data from 5516 participants of the SardiNIA study with a wide range of age at baseline (20–101 years), and a median follow-up time of 13 years (mean 11.5 years; maximum 17.9 years). Baseline CGPs were defined based on the common carotid lumen diameter, wall thickness, and their ratio. Subject-specific rates of change of PWV, blood pressure parameters, body mass index, glucose, and lipids were estimated using linear mixed effects models. Compared to those with typical(t-) CGP, those with dilated hypertrophy (dh-) CGP had a greater longitudinal increase in PWV; this increase was significantly greater among older individuals and men. The greater PWV longitudinal increase in dh-CGP remained significant after adjusting for baseline values and rates of change of covariates. Dilated hypertrophic CGP is independently associated with accelerated increase in age-associated arterial stiffening over time, with a strong association in men than in women. Future studies are needed to examine if this association mediates the increased risk for CVD observed in individuals with hypertrophic cardiac remodelling and the role of retarding it to reduce this risk.

Highlights

• Individuals with dilated hypertrophic geometric phenotypes of the common carotid artery (increased age- and sex-specific wall thickness and lumen diameter) have greater future central arterial stiffening, independently of other determinants of arterial stiffening.

• The dilated hypertrophic phenotype group has a greater age-specific arterial dilation, wall thickening, and stiffness (the arterial aging triad). This suggests that this phenotype is a form of accelerated aging that might explain the worse clinic outcomes observed in this group.

• Understanding the natural history of the carotid geometric phenotype across the lifespan and the determinants of the deleterious progression towards the dilated hypertrophic phenotype are needed to develop interventions that reduce the adverse clinical outcomes associated with it.

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Data Availability

Data associated with this study are available on written request through the corresponding author.

Abbreviations

AGEs:

Advanced glycation end-products

BMI:

Body mass index

BP:

Blood pressure

CCA:

Common carotid artery

CGP:

Carotid geometric phenotype

t-CGP:

Typical CGP

c-CGP:

Concentric

ch-CGP:

Concentric hypertrophic CGP

dh-CGP:

Dilated hypertrophic CGP

CV:

Cardiovascular

DBP:

Diastolic blood pressure

HDL:

High density lipoprotein

HT:

Hypertension/hypertensive

IMT:

Intima-media thickness

LDL:

Low density lipoprotein

MBP:

Mean blood pressure

MMP :

Matrix metalloproteinase

PP:

Pulse pressure

PWV:

Pulse wave velocity

SBP:

Systolic blood pressure

VSMC:

Vascular smooth muscle cells

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Funding

This research was supported in part by the Intramural Research Program of the US National Institutes of Health, National Institute on Aging (No. HHSN271201600005C).

Author information

Authors and Affiliations

  1. Laboratory of Cardiovascular Sciences, National Institute On Aging Intramural Research Program, NIH, 251 Bayview Blvd, Baltimore, MD, 21224, USA

    Majd AlGhatrif, Edward G. Lakatta & Christopher H. Morrell

  2. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Majd AlGhatrif

  3. Loyola University Maryland, Baltimore, MD, USA

    Christopher H. Morrell

  4. Dipartimento of Public Health and Infectious Disease, University “La Sapienza, Rome, Italy

    Danilo Alunni Fegatelli

  5. Istituto Di Ricerca Genetica E Biomedica (IRGB), Consiglio Nazionale Delle Ricerche (CNR), Lanusei, NU, Italy

    Edoardo Fiorillo & Michele Marongiu

  6. Laboratory of Genetics, National Institute On Aging Intramural Research Program, NIH, Baltimore, MD, USA

    David Schlessinger

  7. Istituto Di Ricerca Genetica E Biomedica (IRGB), Consiglio Nazionale Delel Ricerche (CNR), Cagliari, Italy

    Francesco Cucca

  8. Dipartimento Scienze Mediche E Sanita’ Pubblica, Universita’ Di Cagliari, Cagliari, Italy

    Angelo Scuteri

  9. Internal Medicine Unit, Policlinico Universitario Monserrato, AOU Cagliari, Cagliari, Italy

    Angelo Scuteri

Authors
  1. Majd AlGhatrif
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  2. Edward G. Lakatta
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  3. Christopher H. Morrell
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  4. Danilo Alunni Fegatelli
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  5. Edoardo Fiorillo
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  6. Michele Marongiu
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  7. David Schlessinger
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  8. Francesco Cucca
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  9. Angelo Scuteri
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Corresponding author

Correspondence to Majd AlGhatrif.

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The present study complies with the Declaration of Helsinki that the locally appointed ethics committee has approved the research protocol and that informed consent has been obtained from the subjects (or their legally authorized representative).

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The authors declare no competing interests.

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AlGhatrif, M., Lakatta, E.G., Morrell, C.H. et al. Dilated hypertrophic phenotype of the carotid artery is associated with accelerated age-associated central arterial stiffening. GeroScience 45, 1001–1013 (2023). https://doi.org/10.1007/s11357-022-00699-w

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  • DOI: https://doi.org/10.1007/s11357-022-00699-w

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