pulse-wave-velocity-testing-baltimore-longitudinal-study

Pulse Wave Velocity Testing in the Baltimore Longitudinal Study of Aging

Carotid-femoral pulse wave velocity is considered the gold standard for measurements of central arterial stiffness obtained through noninvasive ...

National Institute of Aging

We describe the case of a 70-year-old woman with persistent acantholytic dermatosis. The peculiarity of the case lies in the unusual localization of this dermatosis on the lower lip. A possible relationship with chronic solar damage is discussed.

Persistent acantholytic dermatosis of the lip related to solar damage.

Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas, including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16.

Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients.

Cell therapy has been proposed as an innovative hypothesis to treat acute myocardial infarction and heart failure. However, the mechanism by which stem cells could improve cardiac function remains unclear and many controversies have been arisen in interpretation of experimental and clinical data. Answering the five "WH questions" we discuss the process that has led to consider cell therapy as a new treatment option for myocardial tissue regeneration after ischemic damage. 1) Why should we use stem cells? The rationale derives from the disclosure that apoptosis and regeneration occur at the myocardial level and stem cells migrate from bone marrow to repopulate the damaged cardiac tissue. 2) Which are the most appropriate cells, delivery methods and therapeutic purposes? Adult stem cells can be mobilized or directly transplanted in human hearts to accomplish myocardioneogenesis, neoangiogenesis and/or paracrine effects. 3) Where should we transplant these cells? The infarct border zone seems to be the best place to home and differentiate transplanted cells hampering post-ischemic cardiac remodeling. 4) When should we perform cell therapy? Cell therapy should be performed during or after an acute myocardial infarction: best setting and timing still need to be precisely addressed. 5) Who might be the suitable patient? Further multicenter randomized trials with adequate patient selection are needed to answer this crucial question.

[Cardiac cell therapy: the puzzle is waiting to be solved].

In the last years translation from bench to bedside of findings regarding cardiac cell therapy is swinging between delays and accelerations. Based on experimental studies, clinical trials were started in 2001. To date in Europe more than 900 patients have been treated with cell transplantation or mobilization and new clinical trials are ongoing in many countries. Published data provide a limited idea of current Italian clinical research in this field. This investigation intends to report Italian clinical trials and projects using cell therapy in cardiology.

[Italian clinical trials on cardiac cell therapy: where we are and where are we going?].

A national study group has been established by the Italian Federation of Cardiology to investigate the role of stem/progenitor cell therapy in the treatment of cardiovascular diseases. This article is aimed to point out the challenges and debated issues in the conduction of clinical trials, focusing on the Italian clinical and regulatory existing situation.

[Clinical studies of cardiac cell therapy in Italy].

Patients treated with low-dose anthracyclines often show late onset cardiotoxicity. Recent studies suggest that this form of cardiotoxicity is the result of a progenitor cell disease. In this study we demonstrate that Cord Blood Endothelial Progenitor Cells (EPCs) exposed to low, sub-apoptotic doses of doxorubicin show a senescence phenotype characterized by increased SA-b-gal activity, decreased TRF2 and chromosomal abnormalities, enlarged cell shape, and disarrangement of F-actin stress fibers accompanied by impaired migratory ability. P16( INK4A) localizes in the cytoplasm of doxorubicin-induced senescent EPCs and not in the nucleus as is the case in EPCs rendered senescent by different stimuli. This localization together with the presence of an arrest in G2, and not at the G1 phase boundary, which is what usually occurs in response to the cell cycle regulatory activity of p16(INK4A), suggests that doxorubicin-induced p16( INK4A) does not regulate the cell cycle, even though its increase is closely associated with senescence. The effects of doxorubicin are the result of the activation of MAPKs p38 and JNK which act antagonistically. JNK attenuates the senescence, p16( INK4A) expression and cytoskeleton remodeling that are induced by activated p38. We also found that conditioned medium from doxorubicin-induced senescent cardiomyocytes does not attract untreated EPCs, unlike conditioned medium from apoptotic cardiomyocytes which has a strong chemoattractant capacity. In conclusion, this study provides a better understanding of the senescence of doxorubicin-treated EPCs, which may be helpful in preventing and treating late onset cardiotoxicity.

p38 MAPK and JNK antagonistically control senescence and cytoplasmic p16INK4A expression in doxorubicin-treated endothelial progenitor cells.

The occlusion of a patent foramen ovale (PFO) is one of the most promising and controversial issues of interventional cardiology, with an increasing number of procedures, indications and scientific publications. Although this procedure is considered relatively feasible and efficacious, complications may occur, and the balance between risks and benefits is not always favorable. Data on long-term safety and efficacy are also lacking. From cryptogenic stroke in young patients, indications for occlusion have been extended to include patients with drug-refractory migraine. In this setting, the prevalence of PFO is higher than in the general population, suggesting a possible pathogenetic role. Pathophysiology of this condition and evidence to support occlusion of PFO are incomplete, but a trend towards improving has been reported in many retrospective studies. The only randomized study for migraine benefits in PFO occlusion (MIST) has failed to show a reduction in frequency and intensity of attacks. Selection criteria for patients who will most probably benefit from occlusion are needed. The aim of this brief analysis is to focus the pathophysiological and diagnostic issues on migraine, evaluate their relation with PFO, and review studies to outline percutaneous closure indications.

[Patent foramen ovale and migraine: a causal or casual relationship?].

We examined the relations of central adiposity with left ventricular (LV) diastolic dysfunction in men and women who participated in the Baltimore Longitudinal Study of Aging, a prospective community-based study of older persons. The sample for this cross-sectional analysis included 399 women and 370 men. Central adiposity was estimated using the waist circumference (WC) and global adiposity using the body mass index (BMI). Using data from a comprehensive echocardiographic study that included tissue Doppler imaging, diastolic function was graded according to 3 parameters (E/A ratio, E/Em ratio, and left atrial volume index). In the logistic regression models adjusted for age, gender, cardiovascular risk factors, and hemodynamic parameters, WC and BMI were both independently associated with LV diastolic dysfunction. However, when both WC and BMI were in the same model, only WC remained significantly associated with LV diastolic dysfunction (odds ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.02). In the gender-stratified analyses, WC was significantly associated with LV diastolic dysfunction-independently of BMI-in women (odds ratio 1.08, 95% confidence interval 1.04 to 1.14, p <0.001) but not in men (odds ratio 1.00, 95% confidence interval 0.95 to 1.05, p = 0.91). Additional adjustment for LV mass index failed to modify these relations. In conclusion, the adverse effect of central adiposity on LV diastolic function was independent of general adiposity and more pronounced among women. The effect of visceral adiposity on LV diastolic dysfunction would benefit from confirmation in longitudinal studies.

Contribution of central adiposity to left ventricular diastolic function (from the Baltimore Longitudinal Study of Aging).

An increasing number of patients are being evaluated for percutaneous patent foramen ovale (PFO) closure to prevent recurrent cerebrovascular events, but debate still exists on therapeutic indications and off-label closure device implantation. Pulmonary arteriovenous fistulas (PAVFs) are a rare and heterogeneous malformation prevalently associated with Rendu-Osler-Weber syndrome, and may mimic PFO right-to-left shunt (RLS), leading to unnecessary interventions and in some cases to relapses. Residual shunt is increasingly being observed both after PFO closure and PAVF embolization, even at long-term follow-up, with unclear clinical relevance. This instrumental and possibly therapeutic failure could lie in the presence of pulmonary microfistulas, either pre-existing or following the intervention. Hence, if RLS persists after optimal device placement and reasonable endothelialization time, the presence of a PAVF should be assumed and investigated; if RLS recurs after previous, negative echocontrast studies, presence of device-related complications or pulmonary microfistulas should be taken into consideration.

Sometimes they come back: recurrent noncardiac right-to-left shunt after percutaneous patent foramen ovale closure.

The importance of vitamin D for bone health has long been acknowledged. Recent evidence suggests that vitamin D can also play a role in reducing the risk of several other diseases, including cardiovascular disease.

Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging.

In the literature, only a few cases of deaths related to the use of atypical firearms are present and even more rare are cases of suicide due to multiple lesions.In the present case, the authors report a rare occurrence of suicide due to 4 speargun shots, 3 to the chest and 1 to the head.A complete forensic approach led to attribute the death to acute cardiac failure due to hemopericardium after the injury of the left coronary artery.Scene investigation and autoptic findings allowed authors to hypothesize that injury to the head was a last attempt of suicide, elapsed during the progression of cardiac tamponade.With this report, the authors would like to share knowledge with the forensic community about speargun-related lesions distinguishing them from the very similar ones produced by cold steels.It also shows how it is possible to survive for some time after being shot by such a weapon.

Suicide due to four speargun shots: a case report.

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.

Longitudinal trajectories of arterial stiffness and the role of blood pressure: the Baltimore Longitudinal Study of Aging.

Obesity is independently associated with left ventricular (LV) hypertrophy and thus may be an important modifier of the hypertrophic cardiomyopathy (HC) phenotype. We examined if obesity modifies the clinical presentation, LV morphology, outflow hemodynamics, and exercise tolerance in HC. In this cross-sectional study, 88 obese (body mass index [BMI] ≥30 kg/m(2)) and 154 nonobese (BMI <30 kg/m(2)) patients from the Johns Hopkins HC clinic were compared with respect to a variety of clinical and LV echocardiographic measurements. Obese patients (36.4%) were more likely to report exertional dyspnea (p = 0.04) and chest pain (p = 0.002) and had greater prevalence of hypertension (p = 0.008). LV posterior wall thickness (p = 0.01) but not the septal wall (p ≥0.21) was significantly greater in obese patients, resulting in an increased LV mass index (p = 0.003). No significant differences in LV systolic and diastolic functions were observed, but obesity was associated with higher LV stroke volume (p = 0.03), inducible LV outflow tract gradients (p = 0.045), and chance of developing LV outflow tract obstruction during stress (p = 0.035). In multivariate analysis, BMI was associated with increased posterior (but not septal) wall thickness (β = 0.15, p = 0.02) and LV mass index (β = 0.18, p = 0.005), particularly in those with hypertension. Obesity was also associated with reduced exercise time and functional capacity, and BMI independently correlated with reduced exercise tolerance. In conclusion, obesity is associated with larger LV mass, worse symptoms, lower exercise tolerance, and labile obstructive hemodynamics in HC. The association with increased outflow tract gradients has particular importance as contribution of obesity to the pressure gradients may influence clinical decisions in labile obstructive HC.

Comparison of clinical presentation, left ventricular morphology, hemodynamics, and exercise tolerance in obese versus nonobese patients with hypertrophic cardiomyopathy.

A significant inter-arm difference in systolic blood pressure (IADSBP) has recently been associated with worse cardiovascular outcomes. The authors hypothesized that part of this association is mediated by arterial stiffness, and examined the relationship between significant IADSBP and carotid-femoral pulse wave velocity (CF-PWV) in a sample from the Baltimore Longitudinal Study of Aging. Of 1045 participants, 50 (4.8%) had an IADSBP ≥10 mm Hg at baseline, and 629 had completed data from ≥2 visits (for a total of 1704 visits during 8 years). CF-PWV was significantly higher in patients with an IADSBP ≥10 mm Hg (7.3±1.9 vs 8.2±2, P=.002). Compared with others, patients with IADSBP ≥10 mm Hg also had higher body mass index, waist circumference, and triglycerides; higher prevalence of diabetes; and lower high-density lipoprotein (HDL) cholesterol (P<.001 for all). A significant association with IADSBP ≥10 mm Hg was observed for CF-PWV in both cross-sectional (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06-1.87; P=.01) and longitudinal (OR, 1.15; 95% CI, 1.03-1.29; P=.01) multivariate analyses. Female sex, Caucasian race, high body mass index (plus diabetes and low HDL cholesterol only cross-sectionally) were other independent correlates of IADSBP ≥10 mm Hg. Significant IADSBP is associated with increased arterial stiffness in community-dwelling older adults.

Article	Year
Persistent acantholytic dermatosis of the lip related to solar damage. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics\| PubMed ID: 12539033	2003
Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients. Human pathology\| PubMed ID: 14745721	2004
[Cardiac cell therapy: the puzzle is waiting to be solved]. Giornale italiano di cardiologia (2006)\| PubMed ID: 16700408	2006
[Italian clinical trials on cardiac cell therapy: where we are and where are we going?]. Giornale italiano di cardiologia (2006)\| PubMed ID: 17461361	2007
[Clinical studies of cardiac cell therapy in Italy]. Giornale italiano di cardiologia (2006)\| PubMed ID: 17972429	2007
p38 MAPK and JNK antagonistically control senescence and cytoplasmic p16INK4A expression in doxorubicin-treated endothelial progenitor cells. PloS one\| PubMed ID: 21187925	2010
[Patent foramen ovale and migraine: a causal or casual relationship?]. Giornale italiano di cardiologia (2006)\| PubMed ID: 21416834	2010
Contribution of central adiposity to left ventricular diastolic function (from the Baltimore Longitudinal Study of Aging). The American journal of cardiology\| PubMed ID: 22257709	2012
Sometimes they come back: recurrent noncardiac right-to-left shunt after percutaneous patent foramen ovale closure. Journal of cardiovascular medicine (Hagerstown, Md.)\| PubMed ID: 22395026	2012
Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging. The Journal of clinical endocrinology and metabolism\| PubMed ID: 22767638	2012
Suicide due to four speargun shots: a case report. The American journal of forensic medicine and pathology\| PubMed ID: 23629394	2013
Longitudinal trajectories of arterial stiffness and the role of blood pressure: the Baltimore Longitudinal Study of Aging. Hypertension\| PubMed ID: 24001897	2013
Comparison of clinical presentation, left ventricular morphology, hemodynamics, and exercise tolerance in obese versus nonobese patients with hypertrophic cardiomyopathy. The American journal of cardiology\| PubMed ID: 24079444	2013
Relationship between inter-arm difference in systolic blood pressure and arterial stiffness in community-dwelling older adults. Journal of clinical hypertension (Greenwich, Conn.)\| PubMed ID: 24299691	2013

Marco Canepa

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