Longitudinal Trajectories of Arterial Stiffness and the Role of Blood Pressure The Baltimore Longitudinal Study of Aging
TL;DR: In this paper, the authors collected 2 to 9 serial measures of PWV in 354 men and 423 women of the Baltimore Longitudinal Study of Aging, who were 21 to 94 years of age and free of clinically significant cardiovascular disease.
Abstract: Carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, is an established independent cardiovascular risk factor. Little information is available on the pattern and determinants of the longitudinal change in PWV with aging. Such information is crucial to elucidating mechanisms underlying arterial stiffness and the design of interventions to retard it. Between 1988 and 2013, we collected 2 to 9 serial measures of PWV in 354 men and 423 women of the Baltimore Longitudinal Study of Aging, who were 21 to 94 years of age and free of clinically significant cardiovascular disease. Rates of PWV increase accelerated with advancing age in men more than women, leading to sex differences in PWV after the age of 50 years. In both sexes, not only systolic blood pressure (SBP) ≥140 mm Hg but also SBP of 120 to 139 mm Hg was associated with steeper rates of PWV increase compared with SBP<120 mm Hg. Furthermore, there was a dose-dependent effect of SBP in men with marked acceleration in PWV rate of increase with age at SBP ≥140 mm Hg compared with SBP of 120 to 139 mm Hg. Except for waist circumference in women, no other traditional cardiovascular risk factors predicted longitudinal PWV increase. In conclusion, the steeper longitudinal increase of PWV in men than women led to the sex difference that expanded with advancing age. Age and SBP are the main longitudinal determinants of PWV, and the effect of SBP on PWV trajectories exists even in the prehypertensive range.
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TL;DR: The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing as discussed by the authors.
Abstract: The sirtuins (SIRT1-7) are a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD+ precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others. These advances have demonstrated that it is possible to rationally design molecules that can alleviate multiple diseases and possibly extend lifespan in humans.
526 citations
TL;DR: It is generally thought that hypertension is an aging disorder, and aging-related hypertension is characterized by a significant increase in systolic blood pressure with no change or even a …
Abstract: Although the etiology of essential hypertension remains unknown, it is clear that multiple factors may contribute to the pathogenesis of hypertension. Hypertension is an outcome of the interaction of multiple genetic and environmental factors. Several epidemiological studies indicated that the incidence of arterial stiffness and hypertension and related cardiovascular disease (stroke, myocardial infarction) is higher in the aged than in the young population.1–4 The prevalence of arterial stiffening and hypertension increases with age.1,5 Based on an epidemiological study,6 the prevalence of hypertension is more than doubled in the elderly than in the young population. More than two-thirds of individuals after 65 years of age experience hypertension according to the Seventh Report of the Joint National Committee (JNC-7).7 Therefore, it is generally thought that hypertension is an aging disorder. In recent years, metabolic syndrome and hypertension are increasingly seen in the middle-aged and young populations. In these subpopulations, insulin resistance and overproduction of adipokines impair endothelial and heart function leading to early and accelerated cardiovascular aging. It was reported that premature aging (progeria) is associated with accelerated vascular stiffening or vascular aging.8
Aging is defined as the age-related decline in physiological function essential for survival and fertility. Cardiovascular aging is an important factor that determines life span. The wall of large conduit arteries, especially aorta, thicken and lose elasticity over time, and this process results in an increase in pulse wave velocity, an important and reliable measure of arterial stiffness. The increased arterial stiffness, whatever its underlying causes, would reduce the reservoir/buffering function of the conduit arteries near the heart and increase pulse wave velocity, both of which increase systolic and pulse pressure. Therefore, aging-related hypertension is characterized by a significant increase in systolic blood pressure with no change or even a …
396 citations
TL;DR: Arterial stiffness is emerging as an interesting tissue biomarker for cardiovascular risk stratification and estimation of the individual "biological age", and the evidence and caveat for clinical use of stiffness as surrogate marker of cardiovascular risk are summarized.
330 citations
TL;DR: The vascular phenotype in aging and hypertension is reviewed, focusing on arterial stiffness and vascular remodelling, and the clinical implications of these processes are highlighted and some novel molecular mechanisms of fibrosis and ECM reorganization are discussed.
265 citations
TL;DR: During the past 2 decades, measures of aortic stiffness have emerged as important risk factors for progression of blood pressure and incident cardiovascular disease and elevated CFPWV is associated with high risk for incident hypertension and cardiovascular disease.
Abstract: Hypertension is highly prevalent in the United States and worldwide. In the United States, 1 in 3 adults (≈73 million people) have hypertension. The financial and human costs of hypertension are substantial. The estimated costs attributable to hypertension in the United States alone in 2010 were $70 billion direct costs for medical treatments and $24 billion indirect costs because of lost productivity.1 Awareness and treatment of hypertension have improved considerably during the past several decades: >80% of all people with hypertension are aware of the condition and 75% are using antihypertensive medications.2,3 However, despite enormous effort and treatment-related expenditures, only 53% of those with documented hypertension have their blood pressure controlled.3 Older age (Figure 1), left ventricular hypertrophy, and obesity are important risk factors for uncontrolled or drug-resistant hypertension.4 Importantly, the foregoing are also risk factors for increased aortic stiffness.5
Figure 1.
Hypertension prevalence and control rates as a function of age in the National Health and Nutrition Examination Survey 2003 to 2004. Data derived from Wong et al.44
During the past 2 decades, measures of aortic stiffness have emerged as important risk factors for progression of blood pressure and incident cardiovascular disease. Carotid femoral pulse wave velocity (CFPWV), a measure of aortic wall stiffness, increases markedly with age, particularly after midlife. For example, Framingham Heart Study investigators have shown that the prevalence of CFPWV ≥12 m/s increases from a few percentage before 50 years of age to ≥60% after 70 years of age (Figure 2A). Importantly, elevated CFPWV is associated with high risk for incident hypertension (Figure 2B) and cardiovascular disease (Figure 2C). Figure 2C should be interpreted within the context that a normal value (<95th percentile) for CFPWV in a healthy Framingham Heart Study reference sample <50 years of age was 8.1 …
254 citations
References
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TL;DR: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented and comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99.
Abstract: A method for estimating the cholesterol content of the serum low-density lipoprotein fraction (Sf0-20) is presented. The method involves measurements of fasting plasma total cholesterol, triglyceride, and high-density lipoprotein cholesterol concentrations, none of which requires the use of the preparative ultracentrifuge. Comparison of this suggested procedure with the more direct procedure, in which the ultracentrifuge is used, yielded correlation coefficients of .94 to .99, depending on the patient population compared.
30,622 citations
Boston University1, Rush University Medical Center2, University of Tennessee Health Science Center3, University of Michigan4, University at Buffalo5, University of Mississippi6, University of Miami7, University of Alabama at Birmingham8, Case Western Reserve University9, National Institutes of Health10
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.
24,988 citations
TL;DR: This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.
Abstract: In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.
4,901 citations
TL;DR: This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.
Abstract: Although various studies reported that pulse pressure, an indirect index of arterial stiffening, was an independent risk factor for mortality, a direct relationship between arterial stiffness and all-cause and cardiovascular mortality remained to be established in patients with essential hypertension. A cohort of 1980 essential hypertensive patients who attended the outpatient hypertension clinic of Broussais Hospital between 1980 and 1996 and who had a measurement of arterial stiffness was studied. At entry, aortic stiffness was assessed from the measurement of carotid-femoral pulse-wave velocity (PWV). A logistic regression model was used to estimate the relative risk of all-cause and cardiovascular deaths. Selection of classic risk factors for adjustment of PWV was based on their influence on mortality in this cohort in univariate analysis. Mean age at entry was 50+/-13 years (mean+/-SD). During an average follow-up of 112+/-53 months, 107 fatal events occurred. Among them, 46 were of cardiovascular origin. PWV was significantly associated with all-cause and cardiovascular mortality in a univariate model of logistic regression analysis (odds ratio for 5 m/s PWV was 2.14 [95% confidence interval, 1.71 to 2.67, P<0.0001] and 2.35 [95% confidence interval, 1.76 to 3.14, P<0.0001], respectively). In multivariate models of logistic regression analysis, PWV was significantly associated with all-cause and cardiovascular mortality, independent of previous cardiovascular diseases, age, and diabetes. By contrast, pulse pressure was not significantly and independently associated to mortality. This study provides the first direct evidence that aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with essential hypertension.
3,685 citations
TL;DR: The new standards set by the American Diabetes Association in 2011 recommend universal screening at 24–28 weeks of gestation and an oral glucose tolerance test with a diagnostic fasting plasma glucose of ≥92 mg/dL (4.5 mmol/L) (much lower than the World Health Organization criteria).
Abstract: How to screen and treat gestational diabetes mellitus (GDM) has always been controversial for clinicians and decision makers. The problem is complex, and the evidence is limited. The new standards set by the American Diabetes Association (ADA) in 2011 (1) recommend 1 ) universal screening at 24–28 weeks of gestation (2010 ADA standards recommended selective screening based on risk factors) and 2 ) an oral glucose tolerance test with a diagnostic fasting plasma glucose of ≥92 mg/dL (4.5 mmol/L) (much lower than the World Health Organization [WHO] criteria of ≥126 mg/dL [7.0 mmol/L] commonly used in clinical practice in Europe). Furthermore, diabetes is diagnosed when only one abnormal value is detected (whereas in the 2010 standards two …
3,157 citations