So! What's aging? Is cardiovascular aging a disease?

Lakatta, Edward G.

doi:10.1016/j.yjmcc.2015.04.005

Cited by 187 publications

(133 citation statements)

References 65 publications

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“…due to reduced glomerular filtration rate), or by the combined action of these two mechanisms. Indeed, as recently shown in detail [43,44], several age-associated disorders can cause the death of cardiomyocytes, with the consequent release of sarcolemma proteins, including cTnI and cTnT. On the other hand, circulating cTnI and cTnT are fragmented into molecules small enough to be cleared by the kidney of healthy subjects [45].…”

Section: Agementioning

confidence: 92%

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Clerico

Zaninotto

Ripoli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision ≤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/ calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines.

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Section: Agementioning

confidence: 92%

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Clerico

Zaninotto

Ripoli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…As in AF, failure of proteostasis is also implicated in development of HF owing to myocardial infarction or valvular disease. As is evident in genetic forms of cardiomyopathies, derailed proteostasis has been suggested to contribute to the pathogenesis of acquired cardiomyopathies [131][132][133] . Myocardial samples from patients with myocardial infarction or atrial pressure overload owing to mitral valve disease reveal a substantial amount of myolysis and autophagosomes, indicating derailment of proteostasis (FIG.…”

Section: Derailment Owing To Environmental Stressmentioning

confidence: 99%

Proteostasis in cardiac health and disease

Henning

Brundel²

2017

Nat Rev Cardiol

140

126

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The worldwide increase in life expectancy gives rise to an increasing prevalence of cardiac diseases, which remain the leading cause of disability and death in the developed world [1][2][3] . Currently, the mechanisms under lying how ageing contributes to the initiation or acceler ation of cardiac diseases are essentially unresolved. Prevailing theories of ageing centre on gradual derail ment of cellular protein homeostasis -proteostasis -either by design (genetically) or by 'wear and tear' (environmentally) 3 . Central to the role of proteostasis derailment as a major factor in ageing is the observation that protein function declines over time.Proteins are the most versatile and complex macro molecules and are involved in the proper functioning of every biological process 4 . After synthesis as a poly peptide chain from the genetic code, proper function of a protein relies heavily on its correct folding into a 3D native state and on various post translational modifi cations, mostly involving the addition of chem ical groups (including phosphate, acetate, and carbo hydrate). Protein maturation, transport, and ultimately breakdown is monitored and supported by various classes of proteins, collectively called 'protein quality control' (PQC) [3][4][5] . Balanced proteostasis, therefore, depends on proper PQC and is crucial for cellular and organismal health 6 . The intricate network making up the PQC involves numerous proteins, of which the main players are the chaperones and their regula tors 4,7-9 (assisting in folding and refolding of proteins) and the pathways that clear irreversibly misfolded and aggregation prone proteins (the ubiquitin-proteasome system [UPS] and autophagy systems) 9-11 . With ageing, the gradual accumulation of misfolded or damaged pro teins, together with concomitant failure of PQC, results in proteotoxic stress and compromised defence against reactive oxygen species (ROS) 10 , a process that is likely to be accelerated in various age related diseases includ ing neurodegenerative diseases 12,13 , type 2 diabetes mel litus 14 , cancer 15 , and cardiac diseases [16][17][18][19][20] . In addition to the accumulation of misfolded proteins, ageing is accompanied by an imbalance in the proteome, as indi cated by lowered expression of chaperone, proteaso mal, ribosomal, and mitochondrial proteins, whereas proteins related to oxidative stress are upregulated 21,22 . Although mild impairment of proteostasis extends lifespan in Caenorhabditis elegans, referred to as hormesis, sustained impairment is accompanied by loss of PQC to neutralize this effect 3,5 . Importantly, evidence indicates that the amount of soluble, aggregate prone protein oligomers, rather than the abundance of pro tein aggregates, correlates with disease severity 23,24 . Therefore, protein aggregates, which contain both misfolded proteins and elevated levels of chaper ones, constitute an adequate PQC response, aimed at sequestering potentially harmful protein oligomers, rather than embodying the ultimate cellular threat 25 . This ...

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“…Stiffer arteries increase central blood pressure (BP) by shifting the return of reflected waves to an earlier time during systole 4. These structural changes partially explain the increasing incidence of hypertension, atherosclerosis, and other cardiovascular diseases with age 3, 5, 6…”

Section: Introductionmentioning

confidence: 99%

Racial Differences in Arterial Stiffness are Mainly Determined by Blood Pressure Levels: Results From the ELSA‐Brasil Study

Baldo

Cunha

Ribeiro

et al. 2017

JAHA

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BackgroundBlack people have a higher risk of developing hypertension and presenting higher vascular stiffening. Our aim was to investigate whether the association between race and aortic stiffness could be explained by differences in the primary risk factors.Methods and ResultsWe analyzed data from 11 472 adults (mean age, 51.9±8.9; 53.8% female) self‐reported as white (n=6173), brown (n=3364), or black (n=1935). Their carotid‐to‐femoral pulse wave velocity (cf‐PWV) as well as clinical and anthropometric parameters were measured. cf‐PWV was higher in blacks than in whites or browns (men: white, 9.63±1.81; brown, 9.63±1.88; black, 9.98±1.99; women: white, 8.84±1.64; brown, 9.02±1.68; black, 9.34±1.91; P<0.05). However, this difference disappeared after adjustments for age, mean arterial pressure, heart rate, waist circumference, fasting glucose, and glomerular filtration rate (men: white, 9.68±1.54; brown, 9.68±1.50; black, 9.73±1.52; women: white, 8.93±1.32; brown, 8.98±1.29; black, 9.02±1.32; P>0.05). The association between race and arterial stiffness was significant for brown and black women in the highest cf‐PWV quartile, even after controlling for covariates. There were no differences in the age‐related increase in cf‐PWV among the racial groups after adjustment, confirming the strong effect of age and mean arterial pressure on cf‐PWV revealed by the multiple linear regression.ConclusionsRacial differences in cf‐PWV were mainly attributed to differences in mean arterial pressure and age, although they cannot fully explain the association between race and cf‐PWV in women in the highest cf‐PWV values. This suggests that therapeutic approaches to overcome the effects of aging on the vascular system should focus on blood pressure control, especially in the black population.

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So! What's aging? Is cardiovascular aging a disease?

Cited by 187 publications

References 65 publications

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Proteostasis in cardiac health and disease

Racial Differences in Arterial Stiffness are Mainly Determined by Blood Pressure Levels: Results From the ELSA‐Brasil Study

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