Person-Centered Models for Cardiovascular Care: A Review of the Evidence: A Scientific Statement From the American Heart Association.

Cardiovascular disease remains the leading cause of death and disability in the United States and globally. Disease burden continues to escalate despite technological advances associated with improved life expectancy and quality of life. As a result, longer life is associated with multiple chronic cardiovascular conditions. Clinical guidelines provide recommendations without considering prevalent scenarios of multimorbidity and health system complexities that affect practical adoption. The diversity of personal preferences, cultures, and lifestyles that make up one's social and environmental context is often overlooked in ongoing care planning for symptom management and health behavior support, hindering adoption and compromising patient outcomes, particularly in groups at high risk. The purpose of this scientific statement was to describe the characteristics and reported outcomes in existing person-centered care delivery models for selected cardiovascular conditions. We conducted a scoping review using Ovid MEDLINE, Embase.com, Web of Science, CINAHL Complete, Cochrane Central Register of Controlled Trials through Ovid, and ClinicalTrials.gov from 2010 to 2022. A range of study designs with a defined aim to systematically evaluate care delivery models for selected cardiovascular conditions were included. Models were selected on the basis of their stated use of evidence-based guidelines, clinical decision support tools, systematic evaluation processes, and inclusion of the patient's perspective in defining the plan of care. Findings reflected variation in methodological approach, outcome measures, and care processes used across models. Evidence to support optimal care delivery models remains limited by inconsistencies in approach, variation in reimbursement, and inability of health systems to meet the needs of patients with chronic, complex cardiovascular conditions.

Targeted delivery of VEGF to treat myocardial infarction.

Noninvasive injection of pro-angiogenic compounds such as vascular endothelial growth factor (VEGF) has shown promising results in regenerating cardiac microvasculature. However, these results have failed to translate into successful clinical trials in part due to the short half-life of VEGF in circulation. Increasing the dose of VEGF may increase its availability to the target tissue, but harmful side-effects remain a concern. Encapsulating and selectively targeting VEGF to the MI border zone may circumvent these problems. Anti-P-selectin conjugated immunoliposomes containing VEGF were developed to target the infarct border zone in a rat MI model. Targeted VEGF therapy significantly improves vascularization and cardiac function after an infarction.

COVID-19: An opportunity to engage African Americans and women in research on cardiovascular disease.

INTRODUCTION: African Americans (AA) have been disproportionately affected with the COVID-19 disease experiencing 30%-60% of the deaths, while only making up 13% of the US population. Early data suggest that pregnant women and those with cardiovascular disease (CVD) may experience worse outcomes with severe coronavirus infection. There is an urgent need to incorporate AA and female perspectives into the design of research on the CVD complications related to COVID-19. OBJECTIVES: The goal of this project was to incorporate perspectives of AA and female patients in developing research priorities and AN agenda related to COVID-19. Objectives included: (a) develop a strong, research-ready partnership capable of executing PCOR, (b) creation of a research agenda and a set of priorities on racial/sex-specific CVD disparities in COVID-19 which reflects the perspectives of AA's and women; (c) long-term objective is creation of a set of research questions suitable for clinical research using the AHA Registry. METHODS: The project used principles of active and adult learning within the framework of capacity building to build a strong, patient-centered vision of research needs. Different methods of obtaining patient input were used to identify questions suitable for research using the America Heart Association COVID-19 CVD Quality Improvement Registry: focus groups and town halls to identify concerns and interests vis-à-vis CVD and COVID research; narrative medicine methods collected compelling real-life, COVID-19 health stories; a research advisory council reviewed and prioritized research questions. RESULTS: Outcomes include a replicable method of obtaining patient-oriented input into the creation of a research agenda and a set of research priorities for COVID-19. Outputs include the establishment of a research advisory council and stakeholder training using the PCORI funded, PORTAL program resources; a catalogue of patient generated narratives on COVID-19 experiences in the voice of AAs and women, and a set of research questions suitable for research using the AHA Registry. CONCLUSION: The project created a research ready stakeholder network, ready to develop a research agenda about COVID-19.

Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function.

Recent attempts at rebuilding the myocardium using stem cells have yielded disappointing results. The lack of a supporting vasculature may, in part, explain these disappointing findings. However, concerns over possible side effects have hampered attempts at revascularizing the infarcted myocardium using systemic delivery of proangiogenic compounds. In this study, we develop the technology to enhance the morphology and function of postinfarct neovasculature. Previously, we have shown that the up-regulated expression of endothelial cell adhesion molecules in the myocardial infarction (MI) region provides a potential avenue for selectively targeting drugs to infarcted tissue. After treatment with anti-P-selectin-conjugated liposomes containing vascular endothelial growth factor (VEGF), changes in cardiac function and vasculature post-MI were quantified in a rat MI model. Targeted delivery of VEGF to post-MI tissue resulted in significant increase in fractional shortening and improved systolic function. These functional improvements were accompanied by a 21% increase in the number of anatomical vessels and a 74% increase in the number of perfused vessels in the MI region of treated animals. No significant improvements in cardiac function were observed in untreated, systemic VEGF-treated, nontargeted liposome-treated, or blank immunoliposome-treated animals. Targeted delivery of low doses of proangiogenic compounds to post-MI tissue results in significant improvements in cardiac function and vascular structure.

Prehypertensive African-American women have preserved nitric oxide and renal function but high cardiovascular risk.

AIMS: African-Americans, in particular women, exhibit disproportionate levels of hypertension, inflammation, and oxidative stress compared to other ethnic groups. The relationship between prehypertension, renal function, inflammation, and oxidative stress was examined. METHODS: Twenty-eight African-American women (53.5 +/- 1.1 years) followed an AHA diet and then underwent 24-hour ambulatory BP (ABP) monitoring. Urinary albumin (uAlb), serum and urinary creatinine, glomerular filtration rate (GFR), 24-hour urinary Na(+) excretion, plasma superoxide dismutase, total antioxidant capacity (TAC), urinary (uNOx) and plasma (pNOx) nitric oxide levels, and high-sensitivity C-reactive protein (hsCRP) were measured. RESULTS: When the group was divided by average 24-hour ABP into optimal and nonoptimal groups, a significant difference existed between the groups for uNOx (p = 0.001; nonoptimal: 933.5 +/- 140.4, optimal: 425.0 +/- 52.6 mumol/gCr), and for hsCRP (p = 0.018, nonoptimal: 3.9 +/- 0.7, optimal: 1.9 +/- 0.6 mg/l). Significant inverse relationships existed between hsCRP and uNOx and between uAlb and pNOx in the non-optimal group, between GFR and pNOx in the entire group, and positive association existed between TAC and uNOx in the optimal group. CONCLUSIONS: These results suggest that in African-American women as BP levels rise toward hypertension, the NO/NOS balance may be associated with renal function, and may have implications for CV risk based on their hsCRP levels.

Relative systolic dysfunction in female spontaneously hypertensive rat myocardium.

Hypertension and exercise independently induce left ventricular (LV) remodeling and alter LV function. The purpose of this study was to determine systolic and diastolic LV pressure-volume relationships (LV-PV) in spontaneously hypertensive rats (SHR) with and without LV hypertrophy, and to determine whether 6 mo of exercise training modified the LV-PV in SHR. Four-month-old female SHR (n = 20), were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (approximately 60% peak O2 consumption, 5 days/wk, 6 mo), while age-matched female Wistar-Kyoto rats (WKY; n = 13) served as normotensive controls. The LV-PV was determined using a Langendorff isolated heart preparation at 4 (no hypertrophy: WKY, n = 5; SHR, n = 5) and 10 mo of age (hypertrophy: WKY, n = 8; SHR-SED, n = 8; SHR-TRD, n = 7). At 4 mo, the LV-PV in SHR was similar to that observed in WKY controls. However, at 10 mo of age, a rightward shift in the LV-PV occurred in SHR. Exercise training did not alter the extent of the shift in the LV-PV relative to SHR-SED. Relative systolic function, i.e., relative systolic elastance, was approximately 50% lower in SHR than WKY at 10 mo of age (P < 0.05). Doppler-derived LV filling parameters [early wave (E), atrial wave (A), and the E/A ratio] were similar between groups. LV capacitance was increased in SHR at 10 mo (P < 0.05), whereas LV diastolic chamber stiffness was similar between groups at 10 mo. Hypertrophic remodeling at 10 mo of age in female SHR is manifest with relative systolic decompensation and normal LV diastolic function. Exercise training did not alter the LV-PV in SHR.

Evidence for Therapeutic Patient Education Interventions to Promote Cardiovascular Patient Self-Management: A Scientific Statement for Healthcare Professionals From the American Heart Association.

BACKGROUND: The burden of cardiovascular disease as a chronic illness increasingly requires patients to assume more responsibility for their self-management. Patient education is believed to be an essential component of cardiovascular care; however, there is limited evidence about specific therapeutic patient education approaches used and the impact on patient self-management outcomes. METHODS AND RESULTS: An integrative review of the literature was conducted to critically analyze published research studies of therapeutic patient education for self-management in selected cardiovascular conditions. There was variability in methodological approaches across settings and disease conditions. The most effective interventions were tailored to individual patient needs, used multiple components to improve self-management outcomes, and often used multidisciplinary approaches. CONCLUSIONS: This synthesis of evidence expands the base of knowledge related to the development of patient self-management skills and provides direction for more rigorous research. Recommendations are provided to guide the implementation of therapeutic patient education in clinical practice and the design of comprehensive self-management interventions to improve outcomes for cardiovascular patients.

Improved myocardial beta-adrenergic responsiveness and signaling with exercise training in hypertension.

BACKGROUND: Cardiac responses to beta-adrenergic receptor stimulation are depressed with pressure overload-induced cardiac hypertrophy. We investigated whether exercise training could modify beta-adrenergic receptor responsiveness in a model of spontaneous hypertension by modifying the beta-adrenergic receptor desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca2+ cycling proteins. METHODS AND RESULTS: Female spontaneously hypertensive rats (SHR; age, 4 months) were placed into a treadmill running (SHR-TRD; 20 m/min, 1 h/d, 5 d/wk, 12 weeks) or sedentary group (SHR-SED). Age-matched Wistar Kyoto (WKY) rats were controls. Mean blood pressure was higher in SHR versus WKY (P<0.01) and unaltered with exercise. Left ventricular (LV) diastolic anterior and posterior wall thicknesses were greater in SHR than WKY (P<0.001) and augmented with training (P<0.01). Langendorff LV performance was examined during isoproterenol (ISO) infusions (1x10(-10) to 1x10(-7) mol/L) and pacing stress (8.5 Hz). The peak LV developed pressure/ISO dose response was shifted rightward 100-fold in SHR relative to WKY. The peak ISO LV developed pressure response was similar between WKY and SHR-SED and increased in SHR-TRD (P<0.05). SHR-TRD showed the greatest lusitropic response to ISO (P<0.05) and offset the pacing-induced increase in LV end-diastolic pressure and the time constant of isovolumic relaxation (tau) observed in WKY and SHR-SED. Improved cardiac responses to ISO in SHR-TRD were associated with normalized myocardial levels of GRK2 (P<0.05). SHR displayed increased L-type Ca2+ channel and sodium calcium exchanger abundance compared with WKY (P<0.001). Training increased ryanodine receptor phosphorylation and phospholamban phosphorylation at both the Ser16 and Thr17 residues (P<0.05). CONCLUSIONS: Exercise training in hypertension improves the inotropic and lusitropic responsiveness to beta-adrenergic receptor stimulation despite augmenting LV wall thickness. A lower GRK2 abundance and an increased phosphorylation of key Ca2+ cycling proteins may be responsible for the above putative effects.

Enhanced acidotic myocardial Ca2+ responsiveness with training in hypertension.

PURPOSE: We tested how hypertension-induced compensated hypertrophy, both alone and coupled with exercise training, affects left ventricular (LV) Ca(2+) responsiveness during acidosis. METHODS: Four-month-old female, spontaneously hypertensive rats (SHR) (N = 23) were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (60% VO(2peak), 5 d.wk(-1), 6 months), while Wistar-Kyoto rats (WKY) (N = 12) served as normotensive controls. LV performance was established in response to supraphysiologic Ca(2+) infusion (4 mmol.L(-1)) alone and concomitant with isoproterenol (ISO) (1 x 10 mol.L(-1)) at pH 7.4 and 6.8. RESULTS: HR, rate-pressure product (RPP), and blood pressure were greater in SHR than in WKY (P < 0.05). HR and RPP were attenuated with training. Heart weight and LV anterior wall thickness (diastole) were increased in SHR relative to WKY (P < 0.05) and augmented with training. ISO + 4 mmol.L(-1) [Ca]o resulted in similar LV performance at pH 7.4. At pH 6.8, LV developed pressure was greater in both SHR groups (P < 0.05) versus WKY rats and a twofold increase in the [Ca(2+)]o rescued LV performance to the greatest extent in SHR-TRD. During acidosis, the added stimulus of ISO coupled with elevated [Ca(2+)](o) improved WKY LV performance to near baseline (P < 0.05). Neither elevated [Ca(2+)](o) nor ISO was effective in rescuing LV performance in SHR-SED during acidosis. Phospholamban phosphorylation at Ser(16) and Thr(17) residues were positively correlated with LV functional recovery. Regulatory proteins such as the Na(+)/H(+) exchanger, Na(+)/Ca(2+) exchanger, and the L-type Ca(+) channel were not correlated with LV function. CONCLUSION: Myocardial tolerance to acidosis is improved during the adaptive phase of compensatory hypertrophy. Furthermore, exercise training in SHR induced a myocardial phenotype that preserved Ca(2+) responsiveness during acidosis.

Gender differences in post-infarction hypertrophy in end-stage failing hearts.

OBJECTIVES: We explored whether there are gender differences in cardiac remodeling and whether etiology influences organ and cellular remodeling in advanced heart failure (HF). BACKGROUND: Several studies have shown a survival benefit for women compared to men with symptomatic HF. This observation may be related to gender differences in cardiac remodeling. METHODS: We studied hearts from 100 patients (72 men and 28 women) receiving cardiac transplantation at our institution. Cardiac morphology was assessed with echocardiography and direct measurement of cardiac mass. Cardiac myocyte volume, length, width, cross-sectional area, and contraction were measured using previously validated techniques. RESULTS: Among 50 patients with idiopathic cardiomyopathy (CM), we observed no gender-based differences in cardiac or cellular remodeling. In contrast, among 50 patients with ischemic cardiomyopathy (ICM), the heart weight index was significantly greater in men, and there was a strong trend toward an increased left ventricular (LV) mass index as well. These gender differences in cardiac and LV mass were paralleled by marked gender differences in myocyte volume, such that average myocyte volume was 36% greater in men than in women, in association with a 14% increase in resting cell length. CONCLUSIONS: Our studies demonstrate a multilevel gender difference in post-infarction remodeling, with women exhibiting reduced hypertrophy. Our studies further demonstrate that gender differences in cardiac remodeling in ICM are largely related to fundamental differences in cellular remodeling rather than simply differences in infarct size or expansion. Distinctions observed between ischemic and idiopathic CM suggest that gender may influence local myocardial responses to injury.

Left ventricular reshaping: effects on the pressure-volume relationship.

OBJECTIVE: We tested whether the CardioClasp device (CardioClasp, Inc, Cincinnati, Ohio), a non-blood contact device, would improve left ventricular contractility by acutely reshaping the left ventricle and reducing left ventricular wall stress. METHODS: In dogs (n = 6) 4 weeks of ventricular pacing (210-240 ppm) induced severe heart failure. Left ventricular function was evaluated before and after placement of the CardioClasp device, which uses 2 indenting bars to reshape the left ventricle. Hemodynamics, echocardiography, and Sonometrics crystals dimension (Sonometrics Corporation, London, Ontario, Canada) were measured at steady state and during inferior vena caval occlusion. RESULTS: The CardioClasp device decreased the left ventricular end-diastolic anterior-posterior dimension by 22.8% +/- 1.9%, decreased left ventricular wall stress from 97.3 +/- 22.8 to 67.2 +/- 7.7 g/cm(2) (P =.003), and increased the fractional area of contraction from 21.3% +/- 10.5% to 31.3% +/- 18.1% (P =.002). The clasp did not alter left ventricular end-diastolic pressure, left ventricular pressure, left ventricular dP/dt, or cardiac output. With the CardioClasp device, the slope of the end-systolic pressure-volume relationship was increased from 1.87 +/- 0.47 to 3.22 +/- 1.55 mm Hg/mL (P =.02), the slope of preload recruitable stroke work versus end-diastolic volume was increased from 28.4 +/- 11.0 to 44.1 +/- 23.5 mm Hg (P =.02), and the slope of maximum dP/dt versus end-diastolic volume was increased from 10.6 +/- 4.6 to 18.6 +/- 7.4 mm Hg x s(-1) x mL(-1) (P =.01). The CardioClasp device increased the slope of the end-systolic pressure-volume relationship by 68.0% +/- 21.7%, the slope of preload recruitable stroke work versus end-diastolic volume by 50.7% +/- 18.1%, and the slope of maximum dP/dt versus end-diastolic volume by 85.7% +/- 28.9%. CONCLUSIONS: The CardioClasp device decreased left ventricular wall stress and increased the fractional area of contraction by reshaping the left ventricle. The CardioClasp device was able to maintain cardiac output and arterial pressure. The clasp increased global left ventricular contractility by increasing the slope of the end-systolic pressure-volume relationship, the slope of preload recruitable stroke work versus end-diastolic volume, and the slope of maximum dP/dt versus end-diastolic volume. In patients with heart failure, the CardioClasp device might be effective for clinical application.

Left ventricular systolic performance in failing heart improved acutely by left ventricular reshaping.

OBJECTIVE: If the geometric distortion during dilated heart failure could be corrected, the tension on the myocytes would be decreased, thereby leading to an improvement in left ventricular systolic function. We tested the effects of the CardioClasp (CardioClasp Inc, Pine Brook, NJ), a left ventricular reshaping device, on the failing heart, and our empirical data were compared with computationally derived data. METHODS: Heart failure was induced by 4-week rapid cardiac pacing. At the terminal experiment, an isolated failing heart preparation (isovolumic contraction, n = 5) or an intact failing heart in vivo (n = 7) was used. The effects of the reshaping device on left ventricular performance were assessed by the slopes (Ees) of the left ventricular end-systolic pressure-volume relations, hemodynamics, and echocardiograph before and after placing the CardioClasp on the heart. The change in Ees as the result of left ventricular reshaping was also estimated from computed theoretical analysis and compared with empirical data. RESULTS: There was a significant change in left ventricular dimension after placing the CardioClasp on the heart. In isolated heart preparation, Ees significantly increased from 1.40 +/- 0.44 mm Hg/mL to 2.42 +/- 0.63 mm Hg/mL after placing the device on the heart but returned to the baseline level (1.46 +/- 0.27 mm Hg) after removing it. Left ventricular developed pressure and left ventricular fractional area shortening were significantly increased as the result of left ventricular reshaping. Ees derived from computed theoretical analysis was highly correlated with confirming empirical data. CONCLUSIONS: The CardioClasp can reshape the left ventricle and improve left ventricular systolic performance in failing hearts.

Early and late results of left ventricular reshaping by passive cardiac-support device in canine heart failure.

BACKGROUND: We tested whether the CardioClasp, a passive non-blood-contacting device could decrease excessive geometric burden in dilated cardiomyopathy and improve left ventricular systolic function and contractility by reshaping the left ventricle (LV) and by decreasing LV wall stress (LVWS) without decreasing arterial blood pressure. METHODS: In mongrel dogs (n = 6, the early group; n = 6, the chronic group; 25-27 kg), 4 weeks of rapid right ventricular pacing (210 to 240 bpm) induced dilated cardiomyopathy with heart failure. In the early group, we used hemodynamic data and echocardiography to evaluate LV systolic function immediately after placing the CardioClasp device. In the chronic group, we also evaluated LV systolic function immediately after placing the device on dilated hearts and then left the device in place for 30 days. At the end of 30 days, before explantation of the device, we again assessed LV systolic function. We measured fractional area of contraction (FAC), LVWS, and hemodynamic data in both groups. RESULTS: In the early group, use of the CardioClasp device decreased the LV end-diastolic anterior-to-posterior dimension by 27.8% +/- 2.6% at implantation (p < 0.05). In the chronic group, use of the CardioClasp decreased the LV end-diastolic anterior-to-posterior dimension by 19.4% +/- 2.0% at implantation (p < 0.05) and by 22.0% +/- 3.10% at explantation (p < 0.05). Use of the CardioClasp did not alter LV end-diastolic and peak pressure, LV dP/dts, or cardiac output at implantation or at explantation. In the early group, use of the CardioClasp decreased the LVWS by 43.4% +/- 3.1% at implantation (p < 0.05). In the chronic group, LVWS decreased by 28.8% +/- 2.1% at implantation (p < 0.05) and by 43.3% +/- 5.2% at explantation (p < 0.05). In the early group, FAC increased significantly, by 28.9% +/- 7.8% at implantation (p < 0.05). In the chronic group, FAC increased significantly, by 18% +/- 12% at implantation (p < 0.05) and by 19% +/- 12% at explantation (p < 0.05). CONCLUSIONS: As expected, use of the CardioClasp device increased FAC and decreased LVWS by reshaping the LV. Use of the CardioClasp device maintained cardiac output and arterial pressure. In 30-day experiments, the increased FAC and decreased LVWS were maintained at explantation.

High-resolution Micro-CT evaluation of mid- to long-term effects of estrogen deficiency on rat trabecular bone.

RATIONALE AND OBJECTIVES: Previous studies have shown dramatic short-term bone loss following ovariectomy. The purpose of this study was to evaluate mid- to long-term effects of estrogen deficiency on microarchitecture of tibial trabecular bone using a high-resolution microcomputed tomography (Micro-CT). MATERIALS AND METHODS: Twenty-eight female rats were divided into two equal groups: ovariectomized (OVX, n = 14) and sham-operated (SOVX, n = 14), which in turn were divided into two equal subgroups (euthanized either 6 or 16 weeks after surgery). The left tibia of each animal was scanned with a high-resolution micro-CT (Skyscan 1072 micro-CT system; SkyScan, Aartselaar, Belgium). The Micro-CT system used an X-ray CCD-camera with a cooled 1024 x 1024-pixel 12-bit sensor. RESULTS: Ovariectomy significantly decreased the ratio of bone volume:tissue volume (-42% at 6 weeks and -69% at 16 weeks) and trabecular thickness (-13% at 6 weeks and -30% at 16 weeks), while significantly increasing trabecular separation (+73% at 6 weeks and +100% at 16 weeks) and structure model index (+15% at 6 weeks and +48% at 16 weeks), when compared with SOVX, from 6 to 16 weeks. CONCLUSION: Based on the experimental results, there are alterations of trabecular microarcihtecture in the tibia following mid- and long-term estrogen deficiency. More rod-shaped trabeculae are formed with increasing duration of estrogen deficiency. The high-resolution micro-CT imaging system is useful to evaluate the mid- to long-term trabecular changes seen with estrogen deficiency or osteoporosis.

CardioClasp: a new passive device to reshape cardiac enlargement.

In dilated heart failure, geometric distortions place an extra load on the myocardial cells. If this extra burden can be eliminated, the myocardial wall stress would decrease leading to improved systolic ventricular performance. In a dilated heart failure model, we wanted to see whether the CardioClasp (which uses two indenting bars to reshape the left ventricle [LV] as two widely communicating "lobes" of reduced radius) could improve systolic performance by passively reshaping the LV and reducing the wall stress. In mongrel dogs (n = 7; 25-27 kg), rapid ventricular pacing (210 ppm 1st week to 240 ppm 4th week) induced dilated heart failure. After 4 weeks, LV performance was evaluated at baseline and with the CardioClasp by measuring LV end-diastolic and peak LV systolic pressure, LV +dP/dt, LV -dP/ dt, and cardiac output. With the Clasp on, LV wall stress was reduced to 58.6+/-3.5 from 108.3+/-8.2 g/cm2. The fractional area of contraction (FAC) with the Clasp on (28.4+/-4.4) was significantly increased (p < 0.05) from baseline (20.8+/-4.6) and consistent with improved systolic performance. Cardiac output, LV peak systolic and end-diastolic pressures, and regional myocardial blood flow were unaltered. The Clasp was able to acutely reshape the left ventricle, while preserving the contractile mass, and reduced the tension on the myocardial cells and increased the fractional area of contraction without decreasing the systolic blood pressure.

A standardized exercise intervention differentially affects premenopausal and postmenopausal African-American women.

OBJECTIVE: African-American women represent an understudied population in menopause research yet face greater postmenopausal challenges associated with mortality than their white peers. We investigated the effects of a mild-intensity aerobic exercise training program on markers of mortality risk in both premenopausal and postmenopausal African-American women. METHODS: Sixteen premenopausal women and 19 postmenopausal women underwent 6 months of mild-intensity aerobic exercise training. Measurements included markers of blood lipid and glucose profile, inflammation, kidney function, vascular health, and aerobic fitness before and after the exercise intervention. RESULTS: Before the exercise intervention, the premenopausal and postmenopausal groups only differed in age, low-density lipoprotein, and total cholesterol levels, with the latter two being higher in the postmenopausal group. Both triglycerides and markers of early-stage endothelial dysfunction (CD62E endothelial microparticles) improved in both groups with aerobic exercise training. Aerobic fitness, glomerular filtration rate, body mass index, plasma glucose levels, and markers of late-stage endothelial dysfunction (CD31/CD42b endothelial microparticles) only improved in the premenopausal group. CONCLUSIONS: Mild-intensity aerobic exercise training succeeds in improving some markers of cardiovascular disease and mortality in postmenopausal women. Higher levels of exercise intensity or perhaps additional interventions may need to be considered to further decrease mortality risk in this population.

Effects of moderate aerobic exercise training on vascular health and blood pressure in African Americans.

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise-induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans.

Endothelial activation microparticles and inflammation status improve with exercise training in african americans.

African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to determine the effects of a 6-month aerobic exercise training (AEXT) intervention on the inflammatory biomarkers interleukin-10 (IL-10), interleukin-6 (IL-6), and endothelial microparticle (EMP) CD62E+ and endothelial function assessed by flow-mediated dilation (FMD) in African Americans. A secondary purpose was to evaluate whether changes in IL-10, IL-6, or CD62E+ EMPs predicted the change in FMD following the 6-month AEXT intervention. A pre-post design was employed with baseline evaluation including office blood pressure, FMD, fasting blood sampling, and graded exercise testing. Participants engaged in 6 months of AEXT. Following the AEXT intervention, all baseline tests were repeated. FMD significantly increased, CD62E+ EMPs and IL-6 significantly decreased, and IL-10 increased but not significantly following AEXT. Changes in inflammatory biomarkers did not significantly predict the change in FMD. The change in VO2 max significantly predicted the change in IL-10. Based on these results, AEXT may be a viable, nonpharmacological method to improve inflammation status and endothelial function and thereby contribute to risk reduction for cardiovascular disease in African Americans.

Targeted Delivery of VEGF after a Myocardial Infarction Reduces Collagen Deposition and Improves Cardiac Function.

The development of adjunctive therapies which attenuate adverse remodeling and improve LV function post myocardial infarction (MI) is of significant clinical interest. Previously, we have shown that targeted delivery of therapeutic vascular endothelial growth factor (VEGF) to the infarct border zone significantly increases vascular perfusion and results in improvements in LV function. In this study, we tested the hypothesis that improvements in cardiac function observed with this novel targeted drug delivery system strongly correlate with reductions in collagen deposition in the scar tissue after an MI. Rats received anti-P-selectin conjugated immunoliposomes containing VEGF immediately post-MI. Over 4 weeks, evolutionary changes in LV geometry and function were correlated with collagen deposition and infarct size quantified by Gomori's trichrome and picrosirius red staining. Targeted VEGF treated hearts showed a 37% decrease in collagen deposition in the anterior wall, as well as significant improvements in LV filling pressures. Multi-regression analysis showed that the extent of collagen deposition post MI can be predicted by a linear combination of normalized LV mass and ejection fraction. Targeted delivery of VEGF post-MI results in significant decreases in collagen deposition and adverse remodeling. Improvements in cardiac function in this model are related to degree of collagen deposition and extent of scar formation.

Relationship of visit-to-visit and ambulatory blood pressure variability to vascular function in African Americans.

Visit-to-visit clinic blood pressure variability (BPV) and 24-h BPV have both been identified as independent risk factors for cardiovascular (CV) morbidity and mortality; however, the mechanisms contributing to the increased CV risk as yet are unclear. The purpose of this study was to assess the relationship between BPV and endothelial function in a cohort of putatively healthy African Americans. A total of 36 African Americans who were sedentary, non-diabetic, non-smoking, free of CV and renal disease and not on antihypertensive medication followed an American Heart Association low fat, low salt diet for 6 weeks. Upon completion of the 6-week dietary stabilization period, participants underwent 24-h ambulatory BP monitoring and had their office blood pressure (BP) measured on 3 separate days. Right brachial artery diameter was assessed at rest, during reactive hyperemia (flow-mediated vasodilation: FMD), and after nitroglycerin administration (nitroglycerin-mediated vasodilation: NMD). Participants classified as having decreased endothelial function according to either %FMD or the FMD/NMD ratio had significantly higher 24-h BPV and a trend for higher visit-to-visit BPV when compared with participants with normal endothelial function. Continuous variable analyses revealed a significant positive association between NMD and 24-h diastolic BPV (DBPV). Visit-to-visit systolic BPV (SBPV), 24-h SBPV and 24-h DBPV were all negatively associated with the FMD/NMD ratio. All relationships remained significant after adjustment for age, body mass index and mean BP levels. These results may suggest that BPV is increased in African Americans with decreased endothelial function and is associated with the vascular smooth muscle response to nitric oxide.