Cardiovascular Engineering Inc.

Norwood, MA, United States

Cardiovascular Engineering Inc.

Norwood, MA, United States
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News Article | May 19, 2017

DALLAS - May 19, 2017 - Otherwise healthy young people with high systolic blood pressure over 140 are at greater risk for future artery stiffening linked to an increased risk of stroke as well as possible damage to the kidneys and brain, new research shows. The condition, called isolated systolic hypertension (ISH), occurs in people 18 to 49 who exhibit systolic blood pressure of 140 or higher (versus the optimal of under 120), but a normal diastolic pressure of around 80. Systolic pressure is the top number in a blood pressure reading and diastolic is the bottom number. This study - the largest ever conducted in the U.S. looking at whether young, otherwise healthy ISH patients actually have a cardiovascular problem - suggests the common approach of ignoring higher systolic blood pressure levels in younger adults may be wrong, said study author Dr. Wanpen Vongpatanasin, Director of UT Southwestern Medical Center's Hypertension Program. "I think we should consider treating these patients sooner rather than later," said Dr. Vongpatanasin, Professor of Internal Medicine in the Division of Cardiology at UT Southwestern Medical Center. "I'm concerned that not treating these individuals now will lead to more brain and kidney damage in the future. This condition is not going to get better. It's going to get worse." Although the condition is commonly treated in elderly patients, some physicians have avoided treating it in younger patients, thinking the higher systolic reading was an anomaly related to youth that would self-correct, or perhaps even a sign of a stronger heart since it sometimes showed up in high school athletes, said Dr. Vongpatanasin, who holds the Norman and Audrey Kaplan Chair in Hypertension and the Fredric L. Coe Professorship in Nephrolithiasis in Mineral Metabolism at UT Southwestern. The findings are important because although young people rarely have heart attacks or strokes, the incidence of isolated systolic hypertension in Americans 18 to 39 more than doubled over the last two decades and is now estimated to be about 5 percent, Dr. Vongpatanasin said. Researchers suspect the growing numbers may be related to increasing rates of obesity. This new study, published in the journal Hypertension, found that the threat of aortic stiffness is not only real, but also visible. UT Southwestern researchers examined 2,001 participants in the Dallas Heart Study, a population-based study of more than 6,000 adults in Dallas County. The researchers took cardiovascular magnetic resonance (CMR) pictures of the participants' hearts to assess the condition of the aorta - the major artery that carries oxygenated blood from the heart to the body. A section of the aorta that leads directly from the heart, called the proximal aorta, was the part found to be stiffened in young individuals with high systolic blood pressure. The next step will be to scan kidneys, brains, and hearts of participants from the Dallas Heart Study to determine what effect the aortic stiffening has had. The Dallas Heart Study is the centerpiece of the Donald W. Reynolds Foundation Cardiovascular Clinical Research Center in Dallas, one of three such Centers in the nation, along with those at Harvard and Johns Hopkins. The Dallas Heart Study is a multiethnic population-based study of 6,101 adults from Dallas County designed to: Funding for the study came from the Reynolds Foundation, the National Institutes of Health, the American Heart Association Strategically Focused Research Networks, the Dedman Family Endowed Program for Scholars in Clinical Care, the UT Southwestern George M. O'Brien Kidney Research Core Center, and the Norman and Audrey Kaplan Chair in Hypertension Research. Other researchers involved in this study included Dr. Ian Neeland, Assistant Professor of Internal Medicine; Colby Ayers, Faculty Associate in Clinical Sciences; Dr. Ronald Peshock, Professor of Radiology and Internal Medicine; and Dr. Jarett Berry, Associate Professor of Internal Medicine and of Clinical Sciences, and Dedman Family Scholar in Clinical Care. The national study also included researchers from the University of Mississippi Medical Center, the Northwestern University Feinberg School of Medicine, and Cardiovascular Engineering, Inc., of Norwood, Mass. UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty has received six Nobel Prizes, and includes 22 members of the National Academy of Sciences, 18 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The faculty of more than 2,700 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in about 80 specialties to more than 100,000 hospitalized patients, 600,000 emergency room cases, and oversee approximately 2.2 million outpatient visits a year.

Ben-Shlomo Y.,University of Bristol | Spears M.,University of Bristol | Boustred C.,University of Bristol | May M.,University of Bristol | And 28 more authors.
Journal of the American College of Cardiology | Year: 2014

Objectives The goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors. Background Several studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups. Methods We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. Results Of 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in loge aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p < 0.001) for coronary heart disease, 1.54 (95% CI: 1.34 to 1.78; p < 0.001) for stroke, and 1.45 (95% CI: 1.30 to 1.61; p < 0.001) for CVD. Associations stratified according to sex, diabetes, and hypertension were similar but decreased with age (1.89, 1.77, 1.36, and 1.23 for age ≤50, 51 to 60, 61 to 70, and >70 years, respectively; pinteraction <0.001). After adjusting for conventional risk factors, aPWV remained a predictor of coronary heart disease (HR: 1.23 [95% CI: 1.11 to 1.35]; p < 0.001), stroke (HR: 1.28 [95% CI: 1.16 to 1.42]; p < 0.001), and CVD events (HR: 1.30 [95% CI: 1.18 to 1.43]; p < 0.001). Reclassification indices showed that the addition of aPWV improved risk prediction (13% for 10-year CVD risk for intermediate risk) for some subgroups. Conclusions Consideration of aPWV improves model fit and reclassifies risk for future CVD events in models that include standard risk factors. aPWV may enable better identification of high-risk populations that might benefit from more aggressive CVD risk factor management.

Tsao C.W.,Beth Israel Deaconess Medical Center | DeCarli C.,University of California at Davis | Levy D.,U.S. National Institutes of Health | Larson M.G.,Boston University | Mitchell G.F.,Cardiovascular Engineering Inc.
Neurology | Year: 2013

Objective: To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Methods: Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Results: Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Conclusions: Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes. © 2013 American Academy of Neurology.

Hamburg N.M.,Whitaker Cardiovascular Institute | Hamburg N.M.,Boston University | Larson M.G.,Boston University | Lehman B.T.,Boston University | And 7 more authors.
Hypertension | Year: 2011

Impaired vascular function contributes to the development of clinical cardiovascular disease. The relation between vasodilator function assessed noninvasively in the brachial and digital arteries remains incompletely defined. In the Framingham Offspring, Third Generation and Omni Cohorts, we measured flow-mediated dilation (FMD; n=7031; age 48±13 years; age range, 19 to 88 years; 54% women) and peripheral arterial tonometry (PAT) ratio (n=4352; 55±16 years; age range, 19 to 90 years; 51% women). Abnormal vascular function for each measure was defined by the sex-specific fifth percentile in a reference group free of conventional cardiovascular risk factors. The prevalence of abnormal FMD but not abnormal PAT ratio was higher with advancing age. In multivariable models, higher body mass index was associated with a higher prevalence of both abnormal FMD and PAT ratio. Additional correlates of abnormal FMD included increasing age and higher systolic blood pressure. In contrast, correlates of abnormal PAT ratio included lower systolic blood pressure, increasing total/high-density lipoprotein cholesterol ratio, diabetes, smoking, and lipid-lowering medication. Whereas women had higher FMD and PAT ratios compared with men, using sex-specific reference values, women had a higher prevalence of abnormal brachial and digital vascular function. In participants who had concurrent testing (n=1843), PAT ratio was not significantly associated with FMD in multivariable models. In this large, community-based cohort, brachial and digital measures of vascular function had differing relations with cardiovascular risk factors and were nearly uncorrelated with each other. These results suggest that FMD and PAT provide distinct information regarding vascular function in conduit versus smaller digital vessels. © 2011 American Heart Association, Inc.

Fan L.,Tufts Medical Center | Fan L.,Sun Yat Sen University | Levey A.S.,Tufts Medical Center | Gudnason V.,Icelandic Heart Association | And 10 more authors.
Journal of the American Society of Nephrology | Year: 2015

Current guidelines recommend reporting eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations unless other equations are more accurate, and recommend the combination of creatinine and cystatin C (eGFRcr-cys) as more accurate than either eGFRcr or eGFRcys alone.However, preferred equations and filtration markers in elderly individuals are debated. In 805 adults enrolled in the community-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we measured GFR (mGFR) using plasma clearance of iohexol, standardized creatinine and cystatin C, and eGFR using the CKD-EPI, Japanese, Berlin Initiative Study (BIS), and Caucasian and Asian pediatric and adult subjects (CAPA) equations. We evaluated equation performance using bias, precision, and two measures of accuracy.We first compared the Japanese, BIS, andCAPA equationswith theCKD-EPI equations to determine the preferred equations, and then compared eGFRcr and eGFRcys with eGFRcr-cys using the preferred equations.Mean (SD) agewas 80.3 (4.0) years.Median (25th, 75th)mGFRwas 64 (52, 73)ml/min per 1.73 m2, and the prevalence of decreased GFR was 39% (95% confidence interval, 35.8 to 42.5). Among 24 comparisonswith the other equations,CKD-EPI equations performed better in 9, similar in 13, andworse in 2. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr in four metrics, better than eGFRcys in two metrics, and similar to eGFRcys in two metrics. In conclusion, neither the Japanese, BIS, nor CAPA equations were superior to the CKD-EPI equations in this cohort of community-dwelling elderly individuals. Using the CKD-EPI equations, eGFRcr-cys performed better than eGFRcr or eGFRcys. © 2015 by the American Society of Nephrology.

Koren D.,University of Chicago | Chirinos J.A.,University of Pennsylvania | Katz L.E.L.,Children's Hospital of Philadelphia | Mohler E.R.,University of Pennsylvania | And 3 more authors.
International Journal of Obesity | Year: 2015

Background/Objectives:Obstructive sleep apnea syndrome (OSAS) may be a cardiovascular disease (CVD) risk factor independently of obesity in adults. Pediatric studies have associated OSAS with endothelial dysfunction, but few studies have examined relationships between OSAS and macrovascular sequelae. Our objective was to examine OSAS's independent contribution to macrovascular CVD risk measures in obese adolescents.Subjects/Methods:This cross-sectional observational study was conducted at Children's Hospital of Philadelphia Clinical Research and Academic Sleep Centers, and University of Pennsylvania Vascular Research Unit. Thirty-one obese non-diabetic adolescents underwent anthropometric measurements, overnight polysomnography, fasting laboratory draw and cardiovascular imaging. Cardiovascular outcome measures included maximal carotid intima-media thickness (cIMTmax), a measure of carotid structural changes, and carotid-femoral pulse wave velocity (CFPWV), an aortic stiffness measure whose relationship vis-à-vis OSAS in children has not been previously examined. Carotid diameter and augmentation index (AIx, measuring central pressure augmentation from wave reflections) were assessed. Potential confounding variables examined included blood pressure, lipoproteins, high-sensitivity C-reactive protein, insulin and glucose.Results:The apnea hypopnea index, a primary OSAS measure, was not associated with cIMTmax, carotid diameter, CFPWV or AIx. body mass index (BMI) associated positively with cIMTmax (r=0.52, P=0.006) and CFPWV (r=0.45, P=0.01). Mean asleep end-tidal CO2 was negatively associated with carotid diameter (r=-0.63, P<0.0005). Insulin levels were negatively associated with AIx (r=-0.53, P=0.02).Conclusions:OSAS did not predict carotid structural changes or arterial stiffness independently of BMI in obese adolescents. Higher insulin levels associated with lower central pressure wave augmentation. Finally, long-term hypercapnia may predispose to carotid narrowing. © 2015 Macmillan Publishers Limited All rights reserved.

Thanassoulis G.,U.S. National Institutes of Health | Thanassoulis G.,McGill University | Lyass A.,U.S. National Institutes of Health | Lyass A.,Boston University | And 11 more authors.
Circulation | Year: 2012

Background-Exercise blood pressure (BP) is an important marker of left ventricular hypertrophy, incident hypertension, and future cardiovascular events. Although impaired vascular function is hypothesized to influence the BP response during exercise, limited data exist on the association of vascular function with exercise BP in the community. Methods and Results-Framingham Offspring cohort participants (n=2115, 53% women, mean age 59 years) underwent a submaximal exercise test (first 2 stages of the Bruce protocol), applanation tonometry, and brachial artery flow-mediated dilation testing. We related exercise systolic and diastolic BP at second stage of the Bruce protocol to standard cardiovascular risk factors and to vascular function measures. In multivariable linear regression models, exercise systolic BP was positively related to age, standing BP, standing heart rate, smoking, body mass index, and the total cholesterol-to-high-density cholesterol ratio (P≤0.01 for all). Similar associations were observed for exercise diastolic BP. Carotid-femoral pulse wave velocity (P=0.02), central pulse pressure (P<0.0001), mean arterial pressure (P=0.04), and baseline brachial flow (P=0.002) were positively associated with exercise systolic BP, whereas flow-mediated dilation was negatively associated (P<0.001). For exercise diastolic BP, forward pressure wave amplitude was negatively related (P<0.0001), whereas mean arterial pressure was positively related (P<0.0001). Conclusions-Increased arterial stiffness and impaired endothelial function are significant correlates of a higher exercise systolic BP response. Our findings suggest that impaired vascular function may contribute to exaggerated BP responses during daily living, resulting in repetitive increments in load on the heart and vessels and increased cardiovascular disease risk. © 2012 American Heart Association, Inc.

Weisbrod R.M.,Boston University | Shiang T.,Boston University | Sayah L.A.,Boston University | Fry J.L.,Boston University | And 7 more authors.
Hypertension | Year: 2013

Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension. © 2013 American Heart Association, Inc.

Tsao C.W.,Beth Israel Deaconess Medical Center | Tsao C.W.,U.S. National Institutes of Health | Pencina K.M.,Boston University | Massaro J.M.,Boston University | And 8 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2014

Objective-Arterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease.Approach and Results-Framingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort.Conclusions-In community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study. © 2014 American Heart Association, Inc.

Lam C.S.P.,Framingham Heart Study | Lam C.S.P.,Mayo Medical School | Xanthakis V.,Boston University | Sullivan L.M.,Boston University | And 8 more authors.
Circulation | Year: 2010

Background: Aortic root remodeling in adulthood is known to be associated with cardiovascular outcomes. However, there is a lack of longitudinal data defining the clinical correlates of aortic root remodeling over the adult life course. Methods and Results: We used serial routine echocardiograms in participants of the Framingham Heart Study to track aortic root diameter over 16 years in mid to late adulthood and to determine its short-term (4 years; n=6099 observations in 3506 individuals) and long-term (16 years; n=14 628 observations in 4542 individuals) clinical correlates by multilevel modeling. Age, sex, body size, and blood pressure were principal correlates of aortic remodeling in both short-and long-term analyses (all P≤0.01). Aortic root diameter increased with age in both men and women but was larger in men at any given age. Each 10-year increase in age was associated with a larger aortic root (by 0.89 mm in men and 0.68 mm in women) after adjustment for body size and blood pressure. A 5-kg/m2 increase in body mass index was associated with a larger aortic root (by 0.78 mm in men and 0.51 mm in women) after adjustment for age and blood pressure. Each 10-mm Hg increase in pulse pressure was related to a smaller aortic root (by 0.19 mm in men and 0.08 mm in women) after adjustment for age and body size. Conclusions: These longitudinal community-based data show that aortic root remodeling occurs over mid to late adulthood and is principally associated with age, sex, body size, and blood pressure. The underlying basis for these differences and implications for the development of cardiovascular events deserve further study. © 2010 American Heart Association, Inc.

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