Sex and age differences in the association between sympathetic outflow and central elastic artery wall thickness in humans

Aging is characterized by increased wall thickness of the central elastic arteries (i.e., aorta and carotid arteries), although the mechanisms involved are unclear. Evidence suggests that age-related increases in muscle sympathetic nerve activity (MSNA) may be a contributing factor. However, studies in humans have been lacking. Therefore, we tested the hypothesis that age-related increases in MSNA would be independently associated with carotid artery intima-media thickness (IMT) but not in young women given the reduced influence of MSNA on the vasculature in this group. In 93 young and middle-age/older (MA/O) adults (19–73 yr, 41 women), we performed assessments of MSNA (microneurography) and common carotid IMT and lumen diameter (ultrasonography). Multiple regression that included MSNA and other cardiovascular disease risk factors indicated that MSNA ( P = 0.002) and 24-h systolic blood pressure (BP) ( P = 0.024) were independent determinants of carotid IMT-to-lumen ratio (model R2 = 0.38, P < 0.001). However, when examining only young women (<45 yr), no correlation was observed between MSNA and carotid IMT-to-lumen ratio ( R = −0.01, P = 0.963). MSNA was significantly correlated with IMT-to-lumen ratio while controlling for 24-h systolic BP among young men ( R = 0.49, P < 0.001) and MA/O women ( R = 0.59, P = 0.022). However, among MA/O men, controlling for 24-h systolic BP attenuated the association between MSNA and carotid IMT-to-lumen ratio ( R = 0.50, P = 0.115). Significant age differences in IMT-to-lumen ratio between young and MA/O men ( P = 0.047) and young and MA/O women ( P = 0.023) were removed when adjusting for MSNA (men: P = 0.970; women: P = 0.152). These findings demonstrate an association between higher sympathetic outflow and carotid artery wall thickness with a particular exception to young women. NEW & NOTEWORTHY Increased wall thickness of the large elastic arteries serves as a graded marker for cardiovascular disease risk and progression of atherosclerosis. Findings from the present study establish an independent association between higher sympathetic outflow and carotid artery wall thickness in adults with an exception to young women and extend findings from animal models that demonstrate hypertrophy of vascular smooth muscle following chronic sympathetic-adrenergic stimulation.

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The smoothness index, but not the trough-to-peak ratio predicts changes in carotid artery wall thickness during antihypertensive treatment

Journal of Hypertension ◽

10.1097/00004872-200104000-00007 ◽

2001 ◽

Vol 19 (4) ◽

pp. 703-711 ◽

Cited By ~ 47

Author(s):

Damiano Rizzoni ◽

Maria Lorenza Muiesan ◽

Massimo Salvetti ◽

Maurizio Castellano ◽

Giorgio Bettoni ◽

...

Keyword(s):

Carotid Artery ◽

Wall Thickness ◽

Antihypertensive Treatment ◽

Peak Ratio ◽

Artery Wall ◽

Carotid Artery Wall ◽

Smoothness Index

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Race and Gender Differences in the Association of Lp(a) With Carotid Artery Wall Thickness

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/01.atv.16.3.471 ◽

1996 ◽

Vol 16 (3) ◽

pp. 471-478 ◽

Cited By ~ 51

Author(s):

Pamela J. Schreiner ◽

Gerardo Heiss ◽

H.A. Tyroler ◽

Joel D. Morrisett ◽

C.E. Davis ◽

...

Keyword(s):

Gender Differences ◽

Carotid Artery ◽

Wall Thickness ◽

Artery Wall ◽

Carotid Artery Wall ◽

Race And Gender ◽

And Gender

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Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN rats

Physiological Genomics ◽

10.1152/physiolgenomics.00009.2021 ◽

2021 ◽

Author(s):

Denisha R Spires ◽

Oleg Palygin ◽

Vladislav Levchenko ◽

Elena Isaeva ◽

Christine A. Klemens ◽

...

Keyword(s):

Sexual Dimorphism ◽

Kidney Disease ◽

Diabetic Kidney Disease ◽

Disease Risk ◽

Plasma Cholesterol ◽

Cardiovascular Disease Risk ◽

Glomerular Injury ◽

Diabetic Kidney ◽

Age Related

Diabetic kidney disease (DKD) is a common complication of diabetes, which frequently leads to end-stage renal failure and increases cardiovascular disease risk. Hyperglycemia promotes renal pathologies such as glomerulosclerosis, tubular hypertrophy, microalbuminuria, and a decline in glomerular filtration rate. Importantly, recent clinical data have demonstrated distinct sexual dimorphism in the pathogenesis of DKD in people with diabetes, which impacts both severity- and age-related risk factors. This study aimed to define sexual dimorphism and renal function in a non-obese type 2 diabetes model with the spontaneous development of advanced diabetic nephropathy (T2DN rats). T2DN rats at 12- and over 48-weeks old were used to define disease progression and kidney injury development. We found impaired glucose tolerance and glomerular hyperfiltration in T2DN rats to compare with non-diabetic Wistar control. The T2DN rat displays a significant sexual dimorphism in insulin resistance, plasma cholesterol, renal and glomerular injury, urinary nephrin shedding, and albumin handling. Our results indicate that both male and female T2DN rats developed non-obese type 2 DKD phenotype, where the females had significant protection from the development of severe forms of DKD. Our findings provide further evidence for the T2DN rat strain's effectiveness for studying the multiple facets of DKD.

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Body Weight Change and Carotid Artery Wall Thickness: The Athersclerosis Risk in comunities (ARIC) study

American Journal of Epidemiology ◽

10.1093/oxfordjournals.aje.a009488 ◽

1998 ◽

Vol 147 (6) ◽

pp. 563-573 ◽

Cited By ~ 26

Author(s):

J. Stevens ◽

H.A. Tyroler ◽

J. Cai ◽

C. C. Paton ◽

A. R. Folsom ◽

...

Keyword(s):

Body Weight ◽

Carotid Artery ◽

Wall Thickness ◽

Weight Change ◽

Body Weight Change ◽

Artery Wall ◽

Carotid Artery Wall ◽

Aric Study

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Abstract TP451: Age-associated Changes in the Structure and Biomechanical Properties of Parenchymal Arterioles

Stroke ◽

10.1161/str.47.suppl_1.tp451 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Janice M Diaz-Otero ◽

William F Jackson ◽

Anne M Dorrance

Keyword(s):

Blood Pressure ◽

Extracellular Matrix ◽

Wall Thickness ◽

Biomechanical Properties ◽

Wall Structure ◽

Collagen Deposition ◽

Artery Wall ◽

Wall Area ◽

Age Related ◽

Artery Remodeling

Arterial aging, a phenomenon that we do not fully understand, results in dysfunctional arteries. Age-associated changes in physiological and vascular functions increase the risk of cardiovascular disease. Aging results in peripheral artery remodeling, described as a change in artery size and wall structure. Age-related cerebral artery remodeling could increase the risk of stroke and vascular dementia particularly in situations where comorbidities, such as hypertension, are present. The effects of aging on the biomechanical properties of parenchymal arterioles (PAs) have not been characterized. PAs regulate perfusion of the cerebral microcirculation and are important in determining cerebrovascular resistance. We hypothesized that aging would decrease the lumen diameter, and increase the wall thickness and collagen deposition in PAs from C57Bl/6 mice. PAs were collected from 3-5 month (young; n=8) and 22-24 month (old; n=8) old male mice for assessment of structure by pressure myography. Data collected at 60mmHg are presented as mean ± SEM, young vs. old. Advanced age was associated with increased systolic blood pressure (126 ± 1 vs 145 ± 2mmHg). Aging did not significantly affect the outer (49 ± 5 vs 53 ± 3μm) or lumen (41 ± 5 vs 41 ± 2μm) diameter of the PAs (p > 0.05 for all comparisons). However, the PAs from older mice had increased wall thickness (4 ± 1 vs 6 ± 1μm), wall area (591 ± 96 vs 853 ± 101μm2), and wall-to-lumen ratio (0.10 ± 0.01 vs 0.13 ± 0.01) (p < 0.05 for all comparisons). Wall stress (302 ± 27 vs 220 ± 11 dynes/cm2) was reduced with age. Changes in artery wall structure have been associated with modifications in the components of the extracellular matrix such as collagen and calcium. The PAs from older mice had increased collagen deposition in the wall (427 ± 172 vs 2699 ± 442μm2; p < 0.05) but the number of arteries with calcium deposits was similar between groups (2 ± 1 vs 3 ± 1 positive vessels/area; p > 0.05). Our studies of geriatric mice with high blood pressure suggest that aging is associated with hypertrophic remodeling of the PAs that is accompanied by alterations in the extracellular matrix of the artery wall; these changes could increase the risk of cerebrovascular diseases.

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Assessing Cardiovascular Disease Risk among Young Women with a History of Delivering a Low-Birth-Weight Infant

American Journal of Perinatology ◽

10.1055/s-0032-1323589 ◽

2012 ◽

Vol 30 (04) ◽

pp. 267-274

Author(s):

Elena Kuklina ◽

Brian Bateman ◽

William Callaghan ◽

Patricia Dietz

Keyword(s):

Cardiovascular Disease ◽

Birth Weight ◽

Low Birth Weight ◽

Young Women ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Low Birth Weight Infant ◽

History Of

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Association between neutrophil to lymphocyte ratio and carotid artery wall thickness in healthy pregnant women

European Journal of Obstetrics & Gynecology and Reproductive Biology ◽

10.1016/j.ejogrb.2020.10.034 ◽

2020 ◽

Vol 255 ◽

pp. 98-104 ◽

Cited By ~ 1

Author(s):

Andrea Sonaglioni ◽

Valentina Esposito ◽

Chiara Caruso ◽

Gian Luigi Nicolosi ◽

Stefano Bianchi ◽

...

Keyword(s):

Carotid Artery ◽

Pregnant Women ◽

Wall Thickness ◽

Neutrophil To Lymphocyte Ratio ◽

Artery Wall ◽

Carotid Artery Wall ◽

Lymphocyte Ratio

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Carotid Artery Wall Thickness in Postmenopausal Women Treated with Oral Oestrogens and Oestradiol Implants

Menopause International ◽

10.1177/13621807990050s318 ◽

1999 ◽

Vol 5 (3_suppl) ◽

pp. 17-17

Author(s):

M Brincat ◽

R Galea ◽

Y Muscat Baron

Keyword(s):

Carotid Artery ◽

Postmenopausal Women ◽

Wall Thickness ◽

Artery Wall ◽

Carotid Artery Wall

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Carotid β-stiffness index is associated with slower processing speed but not working memory or white matter integrity in healthy middle-aged/older adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00769.2016 ◽

2017 ◽

Vol 122 (4) ◽

pp. 868-876 ◽

Cited By ~ 10

Author(s):

Lyndsey E. DuBose ◽

Michelle W. Voss ◽

Timothy B. Weng ◽

James D. Kent ◽

Kaitlyn M. Dubishar ◽

...

Keyword(s):

Working Memory ◽

Carotid Artery ◽

Processing Speed ◽

Aortic Stiffness ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Stiffness Index ◽

Middle Aged ◽

Artery Stiffness ◽

Memory Cost

Aging is associated with increased carotid artery stiffness, a predictor of incident stroke, and reduced cognitive performance and brain white matter integrity (WMI) in humans. Therefore, we hypothesized that higher carotid stiffness/lower compliance would be independently associated with slower processing speed, higher working memory cost, and lower WMI in healthy middle-aged/older (MA/O) adults. Carotid β-stiffness ( P < 0.001) was greater and compliance ( P < 0.001) was lower in MA/O ( n = 32; 64.4 ± 4.3 yr) vs. young ( n = 19; 23.8 ± 2.9 yr) adults. MA/O adults demonstrated slower processing speed (27.4 ± 4.6 vs. 35.4 ± 5.0 U/60 s, P < 0.001) and higher working memory cost (−15.4 ± 0.14 vs. −2.2 ± 0.05%, P < 0.001) vs. young adults. Global WMI was lower in MA/O adults ( P < 0.001) and regionally in the frontal lobe ( P = 0.020) and genu ( P = 0.009). In the entire cohort, multiple regression analysis that included education, sex, and body mass index, carotid β-stiffness index (B = −0.53 ± 0.15 U, P = 0.001) and age group (B = −4.61 ± 1.7, P = 0.012, adjusted R2 = 0.4) predicted processing speed but not working memory cost or WMI. Among MA/O adults, higher β-stiffness (B = −0.60 ± 0.18, P = 0.002) and lower compliance (B = 0.93 ± 0.26, P = 0.002) were associated with slower processing speed but not working memory cost or WMI. These data suggest that greater carotid artery stiffness is independently and selectively associated with slower processing speed but not working memory among MA/O adults. Carotid artery stiffening may modulate reductions in processing speed earlier than working memory with healthy aging in humans. NEW & NOTEWORTHY Previously, studies investigating the relation between large elastic artery stiffness, cognition, and brain structure have focused mainly on aortic stiffness in aged individuals with cardiovascular disease risk factors and other comorbidities. This study adds to the field by demonstrating that the age-related increases in carotid artery stiffness, but not aortic stiffness, is independently and selectively associated with slower processing speed but not working memory among middle-aged/older adults with low cardiovascular disease risk factor burden.

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