Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

Lakatta, Edward G.

doi:10.1161/01.cir.0000048894.99865.02

Cited by 939 publications

(580 citation statements)

References 97 publications

Supporting

Mentioning

547

Contrasting

Unclassified

Order By: Relevance

“…The association between arterial stiffness and cognition has been reported 11, 36, 37. The potential underlying mechanisms include the following: (1) excessive pulsatile mechanistic forces on the cerebrovasculature; (2) existing common pathways between arterial stiffness and cognition (eg, environmental and neurohormonal factors), inflammation, and oxidative stress38; and (3) impaired β amyloid clearance and τ‐mediated neurodegeneration 39, 40…”

Section: Discussionmentioning

confidence: 99%

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Yano

Griswold

Wang

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundTo understand how blood pressure (BP) from midlife and beyond is related to cognition in older age, a lifespan approach is needed. We assessed the associations of BP levels and variability from midlife on with subsequent cognitive change.Methods and ResultsThe ARIC (Atherosclerosis Risk in Communities) Study participants underwent 4 clinic BP measurements (visit 1, 2, 3, and 4 BPs) between 1987 and 1998, and their mean levels and average real variability (ARV) were assessed as exposures. A global cognitive z score, estimated from the Delayed Word Recall Test, Digit Symbol Substitution Test, and Word Fluency Test scores, was calculated at 1996 to 1998 (visit 4) and 2011 to 2013 (visit 5). Among 11 408 participants (mean age, 54 years; 56% women; 21% black race), mean systolic BP (SBP)/diastolic BP (DBP) level was 123/72 mm Hg, and ARVSBP/ARVDBP was 11/7 mm Hg. With linear mixed models, 1‐SD increases of ARVSBP (standardized regression coefficient [95% confidence interval], −0.03 [−0.04 to −0.01] points) and ARVDBP (standardized regression coefficient [95% confidence interval], −0.02 [−0.03 to −0.002] points; both P<0.05), but not mean SBP or DBP levels, were associated with lower global cognitive z scores at visit 4. In contrast, mean SBP (standardized regression coefficient [95% confidence interval], −0.04 [−0.06 to −0.02] points) or DBP (standardized regression coefficient [95% confidence interval], 0.04 [0.02–0.06] points; both P<0.001) level, but not ARVSBP or ARVDBP, was associated with change in global cognitive z scores from visits 4 to 5.ConclusionsGreater visit‐to‐visit SBP or DBP variability from midlife on is modestly associated with lower cognitive function, whereas higher mean SBP and lower DBP levels from midlife to later life are modestly associated with cognitive decline in later life.

show abstract

Section: Discussionmentioning

confidence: 99%

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Yano

Griswold

Wang

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that in such patients, hypertension has the same clinical features as in the elderly, involving increased aortic stiffness and a disproportionate elevation of SBP over DBP. 1,2 Furthermore, the predictive value of several CV risk factors decreases with age because of selective survival and the influence of comorbidity on risk factors levels. 40,41 By contrast, vascular stiffness increases steadily with age and could be considered a cumulative measure of previous exposures.…”

Section: Arterial Stiffness and Prognosismentioning

confidence: 99%

“…The diminished elastic recoil of the stiff aorta, combined with the absence of diastolic augmentation from the reflected pressure wave, has the potential to reduce coronary filling. 1,2 With increasing age, there is a gradual shift from diastolic BP (DBP) to SBP and then to pulse pressure (PP) as predictors of cardiovascular (CV) risk, mainly from coronary heart disease. In patients o50 years of age, DBP is the strongest CV predictor.…”

Section: Introductionmentioning

confidence: 99%

Aortic stiffness, inflammation, denutrition and prognosis in the oldest people

et al. 2011

View full text Add to dashboard Cite

Observational studies have shown that some of the classic CV risk factors, namely hypertension or hypercholesterolemia, become nebulous, or even act in the reverse direction, in the oldest people. We investigated whether in the elderly, increased aortic stiffness was associated with higher mortality risk, before and after adjustments on common geriatric confounders. In a cohort of 331 (86 men) subjects aged 470 years (mean age ( ± s.d.): 85 ± 7 years), aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Classical CV risk factors were determined simultaneously, in association with inflammation and denutrition parameters. One hundred and ten subjects died during a 2-year follow-up period. In crude analysis, a positive non-significant trend was observed between PWV and mortality risk. Multivariate Cox regression analysis showed that five parameters entered the prediction model: two were positively related to mortality risk, PWV (P ¼ 0.008) and orosomucoide (P ¼ 0.045), and three were related negatively, total cholesterol (P ¼ 0.006), albumin (P ¼ 0.026) and body weight (P ¼ 0.035). Interaction analysis revealed that the effect of PWV on mortality was increased in the presence of renal dysfunction and increased inflammation. In conclusion, although marginally significant in crude analysis, PWV is a powerful determinant of prognosis in the oldest people taking into account inflammation and denutrition.

show abstract

“…Different pathophysiological stimuli are involved in its development and mediate extracellular matrix (ECM) remodeling leading to vascular stiffness (Lakatta 2003;Wang and Bennett 2012). Cellular senescence is considered to play a causal role in the pathogenesis and development of vascular aging (Kovacic et al 2011a, b;Minamino and Komuro 2007).…”

Section: Introductionmentioning

confidence: 99%

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Chen

Zhao

Jin

et al. 2016

AGE

View full text Add to dashboard Cite

Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl-and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin IIinduced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin IIinduced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, AxlFc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/ FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.

show abstract

Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises

Cited by 939 publications

References 97 publications

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Long‐Term Blood Pressure Level and Variability From Midlife to Later Life and Subsequent Cognitive Change: The ARIC Neurocognitive Study

Aortic stiffness, inflammation, denutrition and prognosis in the oldest people

Testosterone delays vascular smooth muscle cell senescence and inhibits collagen synthesis via the Gas6/Axl signaling pathway

Contact Info

Product

Resources

About