Carl J Pepine

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (863)7286.11 Total impact

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    ABSTRACT: Introduction: Prior studies suggested that a routine invasive approach in the management of non-ST-elevation acute coronary syndrome (NSTE-ACS) is beneficial in men, but the data are less conclusive in women. One study conducted exclusively in women found that routine invasive therapy was associated with a markedly increased risk of major bleeding. This pilot randomized controlled trial compared the safety of a routine invasive versus a selective invasive strategy among women. Methods: Women with NSTE-ACS and an additional high-risk characteristic were randomized to a routine invasive versus a selective invasive strategy. The primary outcome was the risk of major bleeding. The secondary outcome was the first occurrence of all-cause death, myocardial infarction, stroke, re-hospitalization for ACS, or major bleeding within 6 months. Results: Twenty-three women were assigned to routine invasive therapy and 17 to selective invasive therapy. Twenty-seven women (68%) had elevated troponin T (mean 0.33 ng/mL) and/or creatinine kinase-MB (mean 23 ng/mL). The risk of major bleeding was similar with both approaches (P = 0.99). At 6 months, the secondary outcome occurred in 9% of the routine invasive group versus 18% of the selective invasive group (risk ratio = 0.49, 95% confidence interval 0.09-2.63, P = 0.63). Conclusion: This pilot study demonstrated that a routine invasive approach is safe in women. There was suggestion of benefit from routine invasive therapy compared with selective invasive therapy. These data could be used to design an appropriately powered trial to determine the optimal management strategy among women with NSTE-ACS.
    No preview · Article · Dec 2015
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    ABSTRACT: Extensive remodeling of the myocardium is seen in a variety of cardiovascular diseases, including systemic hypertension. Stem cell therapy has been proposed to improve the clinical outcomes of hypertension, and we hypothesized that changes in mechanical properties of the myocardium would accompany the progression of disease and the results of treatment conditions. Using spontaneously hypertensive rats (SHR) as a model of hypertension, we treated 13-week-old hypertensive rats with a single injection of adipose-derived stem cells (ADSC) isolated from a normotensive control. We indented the isolated ventricles of control, untreated sham-injected SHR, and ADSC-treated SHR hearts with a custom cantilever-based system and fit the resulting data to a standard linear solid model. SHR animals had higher blood pressure (198.4±25.9mmHg) and lower ejection fraction (69.9±4.2%) than age-matched control animals (109.0±1.6mmHg, 88.2±1.3%), and increased viscoelastic properties accompanied these clinical changes (right ventricle effective stiffness, SHR: 21.97±5.10kPa, Control: 13.14±3.48kPa). ADSC-treated animals saw improvement in clinical parameters compared to the untreated SHR group, which was also accompanied by a significant restoration of viscoelastic properties of the myocardium (ACSD-treated SHR: 9.77±6.96kPa).
    No preview · Article · Dec 2015 · Journal of the Mechanical Behavior of Biomedical Materials
  • David E. Winchester · Carl J. Pepine
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    ABSTRACT: Angina pectoris is the symptomatic manifestation of transient myocardial ischaemia. At the most fundamental level, angina arises when myocardial oxygen demand exceeds the ability of the coronary circulation to provide adequate oxygen delivery to maintain normal myocardial metabolic function. In vivo, the balance of oxygen demand and delivery is a complex physiological process that can be altered by a variety of interventions. Lifestyle modification is a cornerstone of cardiovascular disease management, with or without angina. Additional pharmaceutical and physical interventions are usually applied to patients with angina. Mechanisms of action for these interventions include heart rate modulation, vascular smooth muscle relaxation, metabolic manipulation, revascularization, and others. A number of these interventions have overlapping mechanisms that target angina. Additionally, some interventions may directly or indirectly prevent or delay adverse outcomes such as myocardial infarction or death. This review summarizes current evidence for many applied ischaemia treatments documented to modify angina and comments on available evidence relating to improvement in cardiovascular outcomes.
    No preview · Article · Dec 2015 · European Heart Journal Supplements
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    ABSTRACT: Aims: The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling. Materials and results: Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041). Conclusions: In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects. Trial registration: clinicaltrials.gov Identifier: NCT01342029.
    No preview · Article · Nov 2015 · European Heart Journal
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    ABSTRACT: In the current study we sought to identify bone marrow-derived mononuclear cell (BMMNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BMMNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-CCTRN trial. Baseline BMMNC immunophenotypes and progenitor-cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2max during the 6-month course of the FOCUSCCTRN study (Group 1, n=17) were compared to those who showed no change or worsened in 1-3 of these endpoints (Group 2, n=61) and to a subset of patients from Group 2 who declined in all 3 functional endpoints (Group 2A, n=11). Group 1 had higher frequencies of B-cell and CXCR4(+) BMMNC subpopulations at study baseline than Group 2 or 2A. Furthermore, patients in Group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in Group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy - even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials.
    No preview · Article · Nov 2015 · Cell Transplantation
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    ABSTRACT: Nonobstructive coronary artery disease (CAD) in women is associated with adverse cardiovascular (CV) outcomes, however information regarding genetic variants that predispose women to nonobstructive CAD is lacking. Women from the Women's Ischemia Syndrome Evaluation Study (WISE) and the St. James Women Take Heart Study (WTH) were genotyped using the Cardio-MetaboChip. WISE enrolled women with symptoms and signs of ischemia referred for coronary angiography; WTH enrolled asymptomatic, community-based women without heart disease. Analyses were conducted using a case (WISE) - control (WTH) design and multivariate logistic regression models to investigate genetic variation associated with likelihood of nonobstructive CAD. One genetic marker, SNP rs2301753 on chromosome 6 in RNF39 achieved chip-wide significance for nonobstructive CAD (p<9.5 x 10(-7)). After adjusting for baseline characteristics, no variants achieved chip-wide significance. However, SNP rs2301753 on chromosome 6 in RNF39 was associated with reduced likelihood of nonobstructive CAD (odds ratio (OR) 0.42 and 95% confidence interval (CI) of 0.29 to 0.68), at a nominal level of p= 5.6x10(-6), while SNP rs12818945 in the ATP2B1 locus on chromosome 12 was associated with increased odds for nonobstructive CAD, (OR 2.38 and 95% CI of 1.63 to 3.45), nominal p=5.8x10(-6). The functions of RNF39 and ATP2B1 raise the possibility that genes involved in cardio-dysfunction may contribute to nonobstructive CAD in Caucasian women and may provide insights into novel approaches for therapy and prevention. If replicated, incorporation of these genetic variants into diagnostic evaluation may identify women at high risk for nonobstructive CAD.
    No preview · Article · Nov 2015 · Physiological Genomics
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    ABSTRACT: High-mobility group box 1 (HMGB1) triggers and amplifies inflammation cascade following ischemic injury, and its elevated levels are associated with adverse clinical outcomes in patients with myocardial infarction (MI). Angiotensin-converting enzyme 2 (ACE2), a key member of vasoprotective axis of the renin-angiotensin system (RAS), regulates cardiovascular functions and exerts beneficial effects in cardiovascular disease. However, the association between HMGB1 and ACE2 has not been studied. We hypothesized that overexpression of ACE2 provides cardioprotective effects against MI via inhibiting HMGB1 and inflammation. ACE2 knock-in (KI) mice and littermate wild-type (WT) controls were subjected to either sham or coronary artery ligation surgery to induce MI. Heart function was assessed 4 weeks after surgery using echocardiography and Millar catheterization. Tissues were collected for histology and analysis of the expression of HMGB1, RAS components, and inflammatory cytokines. ACE2 in the heart of the ACE2 KI mice was 58-fold higher than WT controls. ACE2-MI mice exhibited a remarkable preservation of cardiac function and reduction of infarct size in comparison to WT-MI mice. Notably, ACE2 overexpression significantly reduced the MI-induced increase in apoptosis, macrophage infiltration, and HMGB1 and pro-inflammatory cytokine expression (TNF-α and IL-6). Moreover, in an in vitro study, ACE2 activation prevented the hypoxia-induced cell death and upregulation of HMGB1 in adult cardiomyocytes. This protective effect is correlated with downregulation of HMGB1 and downstream pro-inflammatory cascades, which could be useful for the development of novel treatment for ischemic heart disease. Key messages ACE2 knock-in animals have a normal phenotype. Overexpression of ACE2 favorably shifts the balance of the RAS to vasoprotective axis. Overexpression of ACE2 represses ischemia-induced elevation of HMGB1 and inflammatory cytokines.
    No preview · Article · Oct 2015 · Journal of Molecular Medicine
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    ABSTRACT: Recognition of ischemic heart disease (IHD) is often delayed or deferred in women. Thus, many at risk for adverse outcomes are not provided specific diagnostic, preventive, and/or treatment strategies. This lack of recognition is related to sex-specific IHD pathophysiology that differs from traditional models using data from men with flow-limiting coronary artery disease (CAD) obstructions. Symptomatic women are less likely to have obstructive CAD than men with similar symptoms, and tend to have coronary microvascular dysfunction, plaque erosion, and thrombus formation. Emerging data document that more extensive, nonobstructive CAD involvement, hypertension, and diabetes are associated with major adverse events similar to those with obstructive CAD. A central emerging paradigm is the concept of nonobstructive CAD as a cause of IHD and related adverse outcomes among women. This position paper summarizes currently available knowledge and gaps in that knowledge, and recommends management options that could be useful until additional evidence emerges.
    No preview · Article · Oct 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Objective: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-blocker atenolol. Methods: Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n = 2114). Results: In whites, two polymorphisms near the gene PTPRD (rs12346562 and rs1104514) were associated with DBP response to atenolol (P = 3.2 × 10 and P = 5.9 × 10, respectively) with directionally opposite association for response to hydrochlorothiazide in another group of 228 whites (P = 0.0018 and P = 0.00012). A different polymorphism (rs10739150) near PTPRD was associated with response to atenolol in 150 black hypertensive individuals (P = 8.25 × 10). rs12346562 had a similar trend in association with response to bisoprolol (a different β-blocker) in 207 Finnish men in the genetics of drug responsiveness in essential hypertension study. In addition, an intronic single-nucleotide polymorphism (rs4742610) in the PTPRD gene was associated with resistant hypertension in whites and Hispanics in the international verapamil SR trandolapril study (meta-analysis P = 3.2 × 10). Conclusion: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.
    No preview · Article · Oct 2015 · Journal of Hypertension
  • R David Anderson · Carl J Pepine

    No preview · Article · Sep 2015 · European Heart Journal
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    ABSTRACT: Background Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. Methods CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. Results Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P <.001), systolic pressure time index (r = -0.37, P <.008), and rate pressure product (r = -0.29, P <.04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P <.008) and aortic systolic pressure (P <.01). No other measures contributed significant additional information. Women with CFR 2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P <.001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P <.008), AIx (32 ± 6.6 vs 27 ± 6.6%, P <.003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm × 10, P <.02) and reduced pulse pressure amplification (1.20 ±.07 vs 1.26 ±.10, P <.008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P <.04). Conclusions Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.
    No preview · Article · Aug 2015

  • No preview · Article · Jul 2015 · International journal of cardiology
  • Rajesh Mohandas · R David Anderson · Carl J Pepine

    No preview · Article · Jun 2015 · American Journal of Nephrology
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    ABSTRACT: Adverse pregnancy conditions in women are common and have been associated with adverse cardiovascular and metabolic outcomes such as myocardial infarction and stroke. As risk stratification in women is often suboptimal, recognition of non-traditional risk factors such as hypertensive disorders of pregnancy and premature delivery has become increasingly important. Additionally, such conditions may also increase the risk of cardiovascular disease in the children of afflicted women. In this review, we aim to highlight these conditions, along with infertility, and the association between such conditions and various cardiovascular outcomes and related maternal risk along with potential translation of risk to offspring. We will also discuss proposed mechanisms driving these associations as well as potential opportunities for screening and risk modification.
    Full-text · Article · Jun 2015 · Cardiovascular Drugs and Therapy
  • S Kim · V Rodriguez · M Santisteban · T Yang · Y Qi · M Raizada · C Pepine
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    ABSTRACT: Hypertension (HTN) is a most prevalent risk factor associated with diabetes, obesity, metabolic syndrome and cardiovascular disease, all of which have been recently associated with gut microbial dysbiosis. However, a relationship between gut microbiota and HTN has not been studied. Thus, the objective of our study was to investigate if gut dysbiosis is present in hypertensive patients. We conducted a pilot study using fecal and blood samples obtained from hypertensive (n = 7, systolic BP > 125 mmHg) and normotensive (n = 13, systolic BP < 125 mmHg) patients. Samples were analyzed for Chao richness, Shannon diversity and Pielou evenness using 16 s rRNA sequencing to determine microbiome composition. FACS analysis was used to examine changes in the inflammatory cells levels in these patients. We observed marked decreases in microbial richness and diversity in the HTN patients (Figure 1). In addition, this group also showed a trend towards a decrease in evenness in species from certain genus such as bacteriodetes. Furthermore, increases in myeloid inflammatory cells (94% increase in CD14+ cells, 200% increase in CD11b+ cells) and Th17 cells (700% increase in CD4+ IL17+ cells) were observed in HTN patients compared to normotensives (Figure 2). An increase in the Th17 cells is extremely relevant finding since levels of these cells are regulated by gut-intrinsic mechanisms that generate pro-inflammatory cytokines such as TGF-β1, TNF-α, IL-1β and IL-6. Taken together, these observations suggest that gut microbial dysbiosis plays a key role in HTN and the establishment of a systemic proinflammatory status through regulation of Th17 cell levels. Thus, restoring the gut microbial balance could be a novel therapeutic strategy for the treatment of HTN.(Figure is included in full-text article.).
    No preview · Article · Jun 2015 · Journal of Hypertension
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    ABSTRACT: Obesity is the most important risk factor for hypertension (HTN) and they are strongly associated with chronic inflammation. Treatment resistant hypertension (TRH) subjects, accounting for ∼20% of HTN, have high levels of inflammatory cytokines. This coupled with the fact that the role of adipose stem cells (ASCs) in obesity associated TRH has not been investigated, led us to hypothesize that ASCs from obese-HTN patients expressing heightened inflammatory cytokines contribute to pathogenesis of TRH. Thus, we aim to determine the relationship between ASCs, inflammation, obesity, and TRH. 611 Subjects from the Women's Ischemia Syndrome Evaluation (WISE) study were grouped to normotensive [N, n=99, systolic BP (SBP) 120 ± 12mmHg], controlled HTN (CH, n = 247, SBP 123 ± 11mmHg), and TRH (n = 48, SBP 158 ± 21mmHg). Sera from these subjects were analyzed for high sensitive C-reactive protein (CRP), IL6, serum amyloid A (SAA) and TNF-α level. Human ASCs (hASCs, CD90+/CD11b-/HLA-DR-) were cultured from subcutaneous adipose tissues of overweight-normotensive (ON, n = 6) or obese-hypertensive subjects (OH, n = 6). Rat ASCs (rASCs, CD44+/CD90+/CD34-/CD45-) were isolated from inguinal adipose tissue of normotensive,WKY rats and spontaneously hypertensive rats (SHR). BP positively correlated with the levels of inflammatory cytokines for the WISE analysis. TRH showed two-fold higher CRP (median 0.7), 1.8-fold more IL-6 (median 4.0) and 50% elevated SAA (median 0.8) than N and CH. Additionally, body mass index (BMI) was significantly associated with levels of CRP(r = 0.25, p = 0.0001), IL6(r = 0.14, p = 0.0003), and SAA(r = 0.12, p = 0.0004). hASCs from OH subjects have higher TNF-α, ROS and proliferative capacities than ON subjects. Likewise, rASCs from SHR demonstrated notably higher levels of inflammatory cytokine (TNF-α and IL-1β), ROS and proliferation than WKYrats. Although the magnitude of correlation differed, there was significant positive correlation among BMI, BP, and levels of inflammatory cytokines. Obese subjects are more likely to have TRH than those with lower BMI. Hyper-proliferative ASCs could contribute to elevated inflammation status. These findings imply that ASCs and inflammation plays a critical role in the BP control. Thus, BMI and inflammation status of serum and stem cells may be useful predictors for TRH.
    No preview · Article · Jun 2015 · Journal of Hypertension

  • No preview · Article · May 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Chronic kidney disease (CKD) is more prevalent among women and is associated with adverse cardiovascular events. Among women with symptoms and signs of ischemia enrolled in the Women's Ischemia Syndrome Evaluation (WISE), a relatively high mortality rate was observed in those with no obstructive coronary artery disease. Coronary microvascular dysfunction or reduced coronary flow reserve (CFR) was a strong and independent predictor of adverse outcomes. The objective of this analysis was to determine if renal function was associated with coronary microvascular dysfunction in women with signs and symptoms of ischemia. The WISE was a multicenter, prospective, cohort study of women undergoing coronary angiography for suspected ischemia. Among 198 women with additional measurements of CFR, we determined the estimated glomerular filtration rate (eGFR) with the CKD-EPI equation. We tested the association between eGFR and CFR with regression analysis. The median eGFR was 89 ml/min. The eGFR correlated with CFR (r = 0.22; P = 0.002). This association persisted even after covariate adjustment. Each 10-unit decrease in eGFR was associated with a 0.04-unit decrease in CFR (P = 0.04).There was a strong interaction between eGFR and age (P = 0.006): in those ≥60 years old, GFR was strongly correlated with CFR (r = 0.55; P<0.0001). No significant correlation was noted in those <60 years old. Reduced renal function was significantly associated with lower CFR in women with symptoms and signs of ischemia. Coronary microvascular dysfunction warrants additional study as a mechanism contributing to increased risk of cardiovascular events in CKD.
    Full-text · Article · May 2015 · PLoS ONE
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    ABSTRACT: Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. © 2015 American Heart Association, Inc.
    Full-text · Article · Apr 2015 · Hypertension
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    ABSTRACT: Elevated nighttime blood pressure (BP) and heart rate (HR), increased BP and HR variability, and altered diurnal variations of BP and HR (nighttime dipping and morning surge) in patients with systemic hypertension are each associated with increased adverse cardiovascular events. However, there are no reports on the effect of hypertension treatment on these important hemodynamic parameters in the growing population of hypertensive patients with atherosclerotic coronary artery disease (CAD). This was a pre-specified subgroup analysis of the INternational VErapamil SR-Trandolapril STudy (INVEST), which involved 22,576 clinically stable patients aged ≥50 years with hypertension and CAD randomized to either verapamil SR- or atenolol-based hypertension treatment strategies. The subgroup consisted of 117 patients undergoing 24-hour ambulatory monitoring at baseline and after 1 year of treatment. Hourly systolic and diastolic BP (SBP and DBP) decreased after 1 year for both verapamil SR- and atenolol-based treatment strategies compared with baseline (P<0.0001). Atenolol also decreased hourly HR (P<0.0001). Both treatment strategies decreased SBP variability (weighted standard deviation: P = 0.012 and 0.021, respectively). Compared with verapamil SR, atenolol also increased the prevalence of BP and HR nighttime dipping among prior non-dippers (BP: OR = 3.37; 95% CI: 1.26 – 8.97; P = 0.015; HR: OR = 4.06; 95% CI: 1.35-12.17; P = 0.012) and blunted HR morning surge (+2.8 vs. +4.5 beats/min/hr; P = 0.019). Both verapamil SR- and especially atenolol-based strategies resulted in favorable changes in ambulatory monitoring parameters that have been previously associated with increased adverse cardiovascular events. Trial Registration Clinicaltrials.gov; NCT00133692
    Full-text · Article · Apr 2015 · PLoS ONE

Publication Stats

34k Citations
7,286.11 Total Impact Points

Institutions

  • 1998-2015
    • University of Pittsburgh
      • • Department of Epidemiology
      • • Department of Medicine
      Pittsburgh, Pennsylvania, United States
    • East Tennessee State University
      • Division of Cardiology
      جونسون سيتي، تينيسي, Tennessee, United States
  • 1976-2015
    • University of Florida
      • • Division of Cardiovascular Medicine
      • • Department of Medicine
      • • College of Medicine
      • • Department of Surgery
      Gainesville, Florida, United States
  • 2013
    • University of Otago
      • Department of Medicine (Dunedin)
      Taieri, Otago, New Zealand
  • 2012
    • Allegheny General Hospital
      • Department of Cardiology
      Pittsburgh, Pennsylvania, United States
  • 2007-2012
    • Duke University
      Durham, North Carolina, United States
  • 2011
    • Abbott Northwestern Hospital
      Minneapolis, Minnesota, United States
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1995-2011
    • American College of Cardiology
      Washington, Washington, D.C., United States
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 2010
    • University of Texas Health Science Center at Houston
      • Coordinating Center for Clinical Trials (CCCT)
      Houston, Texas, United States
    • University of Missouri - Kansas City
      Kansas City, Missouri, United States
  • 2009
    • National University (California)
      San Diego, California, United States
  • 2006-2009
    • University of Milan
      Milano, Lombardy, Italy
  • 2004-2009
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, California, United States
    • Rush University Medical Center
      • Department of Preventive Medicine
      Chicago, Illinois, United States
    • University of California, San Francisco
      • Department of Medicine
      San Francisco, California, United States
    • Rhode Island Hospital
      Providence, Rhode Island, United States
  • 2008
    • William Penn University
      Worcester, Massachusetts, United States
  • 2005
    • Rush Medical College
      Chicago, Illinois, United States
    • Abbott Laboratories
      • Abbott Laboratories
      North Chicago, Illinois, United States
    • World Institute for Scientific Exploration (WISE)
      Baltimore, Maryland, United States
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, Michigan, United States
  • 2003
    • University of Oklahoma Health Sciences Center
      Oklahoma City, Oklahoma, United States
  • 2002
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • George Washington University
      • Division of Cardiology
      Washington, D. C., DC, United States
  • 2000
    • University of Sydney
      Sydney, New South Wales, Australia
  • 1992-1999
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
    • United States Department of Veterans Affairs
      Бедфорд, Massachusetts, United States
  • 1997
    • University of Ottawa
      Ottawa, Ontario, Canada
  • 1994-1997
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1996
    • Baylor College of Medicine
      • Section of Cardiology
      Houston, Texas, United States
    • Johns Hopkins Medicine
      • Division of Cardiology
      Baltimore, MD, United States
  • 1991
    • Hospital of the University of Pennsylvania
      Filadelfia, Pennsylvania, United States
    • American Heart Association
      Dallas, Texas, United States
    • Thomas Jefferson University Hospitals
      • Division of Cardiology
      Philadelphia, Pennsylvania, United States
  • 1981
    • Florida Hospital
      Florida, United States
  • 1979
    • Naval Medical Center San Diego
      • Internal Medicine Clinic
      San Diego, California, United States