Publications by authors named "Wanpen Vongpatanasin"

106 Publications

Evidence of reduced efferent renal sympathetic innervation after chemical renal denervation in humans.

Am J Hypertens 2021 03 2. Epub 2021 Mar 2.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, TX.

Background: Renal denervation (RDN) is effective at lowering blood pressure. However, it is unknown if ablative procedures elicit sympathetic denervation of the kidneys in humans. The aim of this investigation was to assess sympathetic innervation of the renal cortex following perivascular chemical RDN, which may be particularly effective at ablating perivascular efferent and afferent nerves.

Methods: Seven hypertensive patients (4F:3M; 50-65 years) completed PET-CT sympathetic neuroimaging of the renal cortex using 11C-Methylreboxetine ( 11C-MRB, norepinephrine transporter ligand) and 6-[ 18F]-fluorodopamine ( 18F-FDA; substrate for the cell membrane norepinephrine transporter) before and 8-weeks after chemical RDN (Peregrine System Infusion Catheter, Ablative Solutions; n=4; 2F:2M) or control renal angiography (n=3; 2F:1M). Patients completed physiological phenotyping including 24-hour ambulatory blood pressure, hemodynamics, muscle sympathetic nerve activity, and 24-hour urine collection.

Results: RDN decreased 11C-MRB-derived radioactivity by ~30% (Δ 11C-MRB/chamber: -0.95 a.u. CI: -1.36 to -0.54, P=0.0002), indicative of efferent renal denervation. In contrast, 18F-FDA -derived radioactivity increased (Δ 18F-FDA/chamber: 2.72 a.u. CI: 0.73 to 4.71, P=0.009), consistent with reduced vesicular turnover. There was no change in either marker in control subjects. Ambulatory systolic blood pressure decreased in 3 of 4 patients (-9 mmHg CI: -27 to 9, P=0.058), and central systolic blood pressure decreased in all subjects (-23 mmHg CI: -51 to 5, P=0.095).

Conclusions: These results are the first to show efferent sympathetic denervation of the renal cortex following RDN in humans. Further studies of mechanisms underlying variable blood pressure lowering in the setting of documented renal denervation may provide insights into inconsistencies in clinical trial outcomes.
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http://dx.doi.org/10.1093/ajh/hpab022DOI Listing
March 2021

TRPV1 (Transient Receptor Potential Vanilloid 1) Sensitization of Skeletal Muscle Afferents in Type 2 Diabetic Rats With Hyperglycemia.

Hypertension 2021 Apr 1;77(4):1360-1371. Epub 2021 Mar 1.

From the Departments of Applied Clinical Research (R.I., S.A.S., M.M.), University of Texas Southwestern Medical Center, Dallas.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15672DOI Listing
April 2021

Assessment of patient and provider attitudes towards therapeutic drug monitoring to improve medication adherence in low-income patients with hypertension: a qualitative study.

BMJ Open 2020 11 27;10(11):e039940. Epub 2020 Nov 27.

Hypertension Section, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States

Objectives: Previous studies have implicated therapeutic drug monitoring (TDM), by measuring serum or urine drug levels, as a highly reliable technique for detecting medication non-adherence but the attitudes of patients and physicians toward TDM have not been evaluated previously. Accordingly, we solicited input from patients with uncontrolled hypertension and their physicians about their views on TDM.

Design: Prospective analysis of responses to a set of questions during semistructured interviews.

Setting: Outpatient clinics in an integrated health system which provides care for a low-income, uninsured population.

Participants: Patients with uncontrolled hypertension with either systolic blood pressure of at least 130 mm Hg or diastolic blood pressure of at least 80 mm Hg despite antihypertensive drugs and providers in the general cardiology and internal medicine clinics.

Primary And Secondary Outcome Measures: Attitudes towards TDM and the potential impact on physician-patient relationship.

Results: We interviewed 11 patients and 10 providers and discussed the findings with 13 community advisory panel (CAP) members. Of the patients interviewed, 91% (10 of 11) and all 10 providers thought TDM was a good idea and should be used regularly to better understand the reasons for poorly controlled hypertension. However, 63% (7 of 11) of patients and 20% of providers expressed reservations that TDM could negatively impact the physician-patient relationship. Despite some concerns, the majority of patients, providers and CAP members believed that if test results are communicated without blaming patients, the potential benefits of TDM in identifying suboptimal adherence and eliciting barriers to adherence outweighed the risks.

Conclusion: The idea of TDM is well accepted by patients and their providers. TDM information if delivered in a non-judgmental manner, to encourage an honest conversation between patients and physicians, has the potential to reduce patient-physician communication obstacles and to identify barriers to adherence which, when overcome, can improve health outcomes.
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http://dx.doi.org/10.1136/bmjopen-2020-039940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703422PMC
November 2020

Association of Genetic West African Ancestry, Blood Pressure Response to Therapy, and Cardiovascular Risk Among Self-Reported Black Individuals in the Systolic Blood Pressure Reduction Intervention Trial (SPRINT).

JAMA Cardiol 2020 Nov 13. Epub 2020 Nov 13.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.

Importance: Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined.

Objective: To determine the association between the proportion of West African ancestry with the response to antihypertensive medication, BP control, kidney function, and risk of adverse cardiovascular (CV) events among self-identified Black individuals in the Systolic Blood Pressure Intervention Trial (SPRINT).

Design, Setting, And Participants: This post hoc analysis of the SPRINT trial incorporated data from a multicenter study of self-identified Black participants with available West African ancestry proportion, estimated using 106 biallelic autosomal ancestry informative genetic markers. Recruitment started on October 20, 2010, and ended on August 20, 2015. Data were analyzed from May 2020 to September 2020.

Main Outcomes And Measures: Trajectories of BP and kidney function parameters on follow-up of the trial were assessed across tertiles of the proportion of West African ancestry using linear mixed-effect modeling after adjustment for potential confounders. Multivariable adjusted Cox models evaluated the association of West African ancestry with the risk of composite CV events (nonfatal myocardial infarction, CV death, and heart failure event).

Results: Among 2466 participants in the current analysis (1122 women [45.5%]; median West African ancestry, 81% [interquartile range, 73%-87%]), there were 120 composite CV events (4.9%) over a mean (SD) of 3.2 (0.9) years of follow-up. At baseline, mean (SD) high-density lipoprotein cholesterol levels were higher (tertile 3: 56.5 [15.0] mg/dL vs tertile 1: 54.2 [14.9] mg/dL; P = .006), smoking prevalence (never smoking: tertile 3: 367 [47.9%] vs tertile 1: 372 [42.2%]; P = .009) and mean (SD) Framingham Risk scores (tertile 3: 16.7 [9.7] vs tertile 1: 18.1 [10.2]; P = .01) were lower, and baseline BP was not different across increasing tertiles of West African ancestry. On follow-up, there was no evidence of differences in longitudinal trajectories of BP, kidney function parameters, or left ventricular mass (Cornell voltage by electrocardiogram) across tertiles of West African ancestry in either intensive or standard treatment arms. In adjusted Cox models, higher West African ancestry was associated with a lower risk of a composite CV event after adjustment for potential confounders (adjusted hazard ratio per 5% higher West African ancestry, 0.92 [95% CI, 0.85-0.99]).

Conclusions And Relevance: Among self-reported Black individuals enrolled in SPRINT, the trajectories of BP, kidney function, and left ventricular mass over time were not different across tertiles of the proportion of West African ancestry. A higher proportion of West African ancestry was associated with a modestly lower risk for CV events. These findings suggest that extrinsic and structural societal factors, more than genetic ancestry, may be the major drivers of the well-established racial disparity in cardiovascular health associated with hypertension.
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http://dx.doi.org/10.1001/jamacardio.2020.6566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666434PMC
November 2020

A case of chemotherapy-induced coronary vasospasm in a patient with colorectal cancer.

J Cardiol Cases 2020 Sep 10;22(3):117-120. Epub 2020 Jun 10.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Colorectal cancer kills nearly 700,000 people each year worldwide. The use of chemotherapeutic agents in the treatment of colorectal cancer has broadened considerably over the past few decades. The cardiovascular care of patients being treated with these agents has received increasing attention over recent years due to the known cardiovascular toxicities associated with certain treatment regimens, but there may still be unidentified cardiovascular toxicities. Here we present a case of a patient with colorectal cancer without any modifiable cardiovascular risk factors who experienced coronary vasospasm shortly after initiation of therapy with 5-flourouracil, leucovorin, and oxaliplatin with bevacizumab, despite having previously tolerated boluses of 5-flourouracil alone without incident. Coronary vasospasm attributed to this combination of chemotherapy has never before been reported. Additionally, our case and other available literature demonstrate the efficacy of dihydropyridine calcium channel blocker therapy in treatment of vasospasm induced by chemotherapeutic agents. < Many chemotherapeutic agents have known cardiotoxicities, but there may still be unidentified cardiovascular toxicities. Here we report a case of coronary vasospasm attributed to the combination of a 5-flourouracil containing regimen (FOLFOX) and bevacizumab. Vasospasm attributed to this combination of chemotherapy has never been reported, and our patient was successfully treated with dihydropyridine calcium channel blocker therapy.>.
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http://dx.doi.org/10.1016/j.jccase.2020.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452347PMC
September 2020

Baseline Prevalence of Polypharmacy in Older Hypertensive Study Subjects with Elevated Dementia Risk: Findings from the Risk Reduction for Alzheimer's Disease Study (rrAD).

J Alzheimers Dis 2020 ;77(1):175-182

Pennington Biomedical Research Center, Baton Rouge, LA, USA.

Background: Little is known about the prevalence of polypharmacy, the taking of five or more medications a day, in older adults with specific dementia risk factors.

Objective: To examine the prevalence of polypharmacy in participants at baseline in a vascular risk reduction focused Alzheimer's disease (rrAD) trial targeting older patients with hypertension and elevated dementia risk.

Methods: We conducted a detailed review of medications in a cross-sectional study of community-dwelling older adults with hypertension and elevated dementia risk. Medications were identified in a structured interview process with an onsite pharmacist or qualified designee. Polypharmacy was defined as use of five or more medications on a regular basis. Descriptive analyses were conducted on the sample as well as direct comparisons of subgroups of individuals with hypertension, diabetes, and hyperlipidemia.

Results: The 514 rrAD participants, mean age 68.8 (standard deviation [sd] 6), reported taking different combinations of 472 unique medications at their baseline visit. The median number of medications taken by participants was eight [Range 0-21], with 79.2% exhibiting polypharmacy (n = 407). Sites differed in their prevalence of polypharmacy, χ2(3) = 56.0, p < 0.001. A nearly identical percentage of the 2,077 prescribed (51.8%) and over the counter (48.2%) medications were present in the overall medication profile. The presence of diabetes (87.5%), hyperlipidemia (88.2%), or both (97.7%) was associated with a higher prevalence of polypharmacy than participants who exhibited hypertension in the absence of either of these conditions (63.2%), χ2(3) = 35.8, p < 0.001.

Conclusion: Participants in a dementia risk study had high levels of polypharmacy, with the co-existence of diabetes or hyperlipidemia associated with a greater prevalence of polypharmacy as compared to having hypertension alone.
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http://dx.doi.org/10.3233/JAD-200122DOI Listing
January 2020

Insulin resistance is associated with an exaggerated blood pressure response to ischemic rhythmic handgrip exercise in nondiabetic older adults.

J Appl Physiol (1985) 2020 07 25;129(1):144-151. Epub 2020 Jun 25.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.

Patients with type 2 diabetes display an exaggerated pressor response to exercise. However, evidence supporting the association between the magnitude of the pressor response to exercise and insulin resistance-related factors including hemoglobin A1c (HbA1c) or homeostatic model assessment of insulin resistance (HOMA-IR) in nondiabetic subjects has remained sparse and inconclusive. Thus we investigated the relationship between cardiovascular responses to exercise and insulin resistance-related factors in nondiabetic healthy men ( = 23) and women ( = 22) above 60 yr old. We measured heart rate (HR) and blood pressure (BP) responses during: isometric handgrip (IHG) exercise of 30% maximal voluntary contraction, a period of skeletal muscle ischemia (SMI) induced by tourniqueting the arm after IHG, and rhythmic dynamic handgrip (DHG) exercise during SMI. Greater diastolic BP (DBP) responses to DHG with SMI was associated with male sex ( = 0.44, = 0.02) and higher HbA1c ( = 0.33, = 0.03), heart-ankle pulse wave velocity (haPWV) ( = 0.45, < 0.01), and resting systolic BP (SBP) ( = 0.36, = 0.02). HbA1c persisted as a significant determinant explaining the variance in the DBP response to DHG with SMI in multivariate models despite adjustment for sex, haPWV, and resting SBP. It was also determined that the DBP response to DHG with SMI in a group in which HOMA-IR was abnormal (Δ33 ± 3 mmHg) was significantly higher than that of groups in which HOMA-IR was at intermediate (Δ20 ± 4 mmHg) and normal (Δ23 ± 2 mmHg) levels. These data suggest that even in nondiabetic older adults, insulin resistance is related to an exaggerated pressor response to exercise especially when performed under ischemic conditions. The diastolic blood pressure response to rhythmic dynamic handgrip exercise under ischemic conditions was demonstrated to be correlated with insulin resistance-related factors in nondiabetic older adults. This finding provides important insight to the prescription of exercise in this particular patient population as the blood pressure response to exercise, especially under ischemic conditions, could be exaggerated to nonsafe levels.
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http://dx.doi.org/10.1152/japplphysiol.00247.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938775PMC
July 2020

Broader adaptive range of sympathetic burst size in response to blood pressure change in older women with greater arterial stiffness.

J Physiol 2020 08 16;598(16):3331-3341. Epub 2020 Jun 16.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Texas, USA.

Key Points: In this study, we focused on muscle sympathetic nerve activity (MSNA) burst size and occurrence separately as subcomponents of the sympathetic baroreflex in older adults, and we found that the distribution (variation) of burst size against burst occurrence was greater in women than men. Older women had greater carotid artery stiffness compared with older men, while blood pressure (BP) distribution (variation) was comparable between sexes. Sympathetic baroreflex sensitivity assessed with burst incidence was less sensitive as the carotid artery became stiffer in older men and women, while that assessed with burst area was more sensitive as the carotid artery became stiffer in older women but not in older men. These results help us understand the mechanisms underlying the compensation for the impaired response of MSNA burst occurrence in older women with greater carotid artery stiffness to regulate BP similar to that in older men.

Abstract: There are sex differences in arterial stiffness and neural control of blood pressure (BP) among older adults. We examined whether the sympathetic response to BP is greater in older women than men in burst size but not burst occurrence. Burst occurrence and size were assessed with burst interval and area of muscle sympathetic nerve activity, respectively, and the distributions of these indices were evaluated by range during supine rest in 61 healthy older subjects (30 men (69 ± 6 years) and 31 women (68 ± 6 years); means ± SD). Also, we analysed sympathetic baroreflex sensitivity (BRS) with burst occurrence and area simultaneously. Carotid β-stiffness was measured with B-mode ultrasonic image and carotid BP. The range of burst interval was smaller in older women than men (P = 0.002), while there was no difference in the range of burst area. Carotid β-stiffness was greater in older women than men (6.7 ± 2.7 vs. 5.1 ± 2.7, P = 0.027). Sympathetic BRS assessed with burst incidence was lower in older women than men (-2.3 ± 1.4 vs. -3.3 ± 1.4 bursts·100 beats  mmHg , P = 0.007), while this sex difference was observed when assessed with burst area after adjusting for carotid β-stiffness (-116.1 ± 135.0 vs. -185.9 ± 148.2 a.u. burst  mmHg , P = 0.040), but not before. Sympathetic BRS assessed with burst area was negatively (more sensitive) correlated with carotid β-stiffness in older women (r = -0.53, P = 0.002) but not men. These data suggest that the response of burst size within each burst is augmented for the baroreflex BP control despite the impaired response of burst occurrence in older women with greater carotid stiffness.
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http://dx.doi.org/10.1113/JP279877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429302PMC
August 2020

Skeletal Muscle Reflex-Induced Sympathetic Dysregulation and Sensitization of Muscle Afferents in Type 1 Diabetic Rats.

Hypertension 2020 04 17;75(4):1072-1081. Epub 2020 Feb 17.

From the Department of Applied Clinical Research (R.I., N.H., S.A.S., M.M.), University of Texas Southwestern Medical Center, Dallas.

The blood pressure response to exercise is exaggerated in the type 1 diabetes mellitus (T1DM). An overactive exercise pressor reflex (EPR) contributes to the potentiated pressor response. However, the mechanism(s) underlying this abnormal EPR activity remains unclear. This study tested the hypothesis that the heightened blood pressure response to exercise in T1DM is mediated by EPR-induced sympathetic overactivity. Additionally, the study examined whether the single muscle afferents are sensitized by PKC (protein kinase C) activation in this disease. Sprague-Dawley rats were intraperitoneally administered either 50 mg/kg streptozotocin (T1DM) or saline (control). At 1 to 3 weeks after administration, renal sympathetic nerve activity and mean arterial pressure responses to activation of the EPR, mechanoreflex, and metaboreflex were measured in decerebrate animals. Action potential responses to mechanical and chemical stimulation were determined in group IV afferents with pPKCα (phosphorylated-PKCα) levels assessed in dorsal root ganglia. Compared with control, EPR (58±18 versus 96±33%; <0.05), mechanoreflex (21±13 versus 51±20%; <0.05), and metaboreflex (40±20 versus 88±39%; <0.01) activation in T1DM rats evoked significant increases in renal sympathetic nerve activity as well as mean arterial pressure. The response of group IV afferents to mechanical (18±24 versus 61±45 spikes; <0.01) and chemical (0.3±0.4 versus 1.6±0.8 Hz; <0.01) stimuli were significantly greater in T1DM than control. T1DM rats showed markedly increased pPKCα levels in dorsal root ganglia compared with control. These data suggest that in T1DM, abnormally muscle reflex-evoked increases in sympathetic activity mediate exaggerations in blood pressure. Further, sensitization of muscle afferents, potentially via PKC activation, may contribute to this abnormal circulatory responsiveness.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7117783PMC
April 2020

Resistant hypertension-defining the scope of the problem.

Prog Cardiovasc Dis 2020 Jan - Feb;63(1):46-50. Epub 2019 Dec 19.

Hypertension Section, University of Texas Southwestern Medical Center, Dallas, TX; Cardiology Division, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address:

The updated scientific statement by the American Heart Association has defined resistant hypertension (HTN;RH) as uncontrolled blood pressure (BP) ≥ 130/80 mmHg, despite concurrent use of 3 anti-HTN drug classes comprising a calcium channel blocker, a blocker of renin-angiotensin system, and a thiazide diuretic, preferably chlorthalidone. Using the updated BP criteria, the prevalence of RH in the United States is found to be modestly increased by approximately 3-4% among treated population. Meta-analysis of observational studies have demonstrated that pseudo-RH from white coat HTN or medication nonadherence is as much common as the truly RH. Thus, screening for pseudo-resistance in the evaluation of all apparent RH is of utmost importance as diagnosis of white-coat HTN requires no treatment, while medication nonadherence would benefit from identifying and targeting barriers to adherence.
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http://dx.doi.org/10.1016/j.pcad.2019.12.006DOI Listing
May 2020

Sex Differences in the Sympathetic Neural Recruitment and Hemodynamic Response to Head-Up Tilt in Older Hypertensives.

Hypertension 2020 02 9;75(2):458-467. Epub 2019 Dec 9.

From the Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas (M.B.B., Y.O., J.-K.Y., B.D.L., Q.F.).

This study tested the hypothesis that older hypertensive women display augmented pressor responses and aberrant sympathetic neural discharge patterning in response to orthostatic stress versus older hypertensive men. We evaluated, in older hypertensive and normotensive men and women (n=12 each group), blood pressure, heart rate, cardiac index (acetylene rebreathing), total peripheral resistance, and muscle sympathetic nerve activity (microneurography) at baseline (supine; 3 minutes) and during graded head-up tilt (30° for 5 minutes and 60° for 20 minutes). Sympathetic action potential discharge patterns were studied using wavelet-based methodology. In the upright posture, systolic and diastolic blood pressure responses were greater in hypertensive women versus hypertensive men and normotensive women (<0.05). No differences existed in the heart rate, stroke index, or cardiac index response between groups; however, the total peripheral resistance response throughout graded head-up tilt was markedly greater in hypertensive women (<0.01). Yet, the increase in integrated muscle sympathetic nerve activity burst frequency and burst incidence were similar between hypertensive women and men in the supine and upright postures. However, the increase in the mean action potential content per integrated burst and recruitment of previously dormant, larger-sized action potentials during 60° head-up tilt was greater in hypertensive women versus hypertensive men and normotensive women (<0.001). Therefore, total sympathetic action potential firing frequency was markedly greater in hypertensive women throughout 60° head-up tilt (<0.001). In conclusion, older hypertensive women displayed exaggerated pressor and peripheral vasoconstrictor responses to orthostasis versus hypertensive men, under conditions of augmented and aberrant sympathetic neural recruitment, rather than increased burst frequency, in the upright posture.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004478PMC
February 2020

Incorporation of Biomarkers Into Risk Assessment for Allocation of Antihypertensive Medication According to the 2017 ACC/AHA High Blood Pressure Guideline: A Pooled Cohort Analysis.

Circulation 2019 12 11;140(25):2076-2088. Epub 2019 Nov 11.

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (A.P., K.V.P., W.V., C.A., J.D.B. J.A.d.L., P.H.J).

Background: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear.

Methods: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups.

Results: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively.

Conclusions: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043337DOI Listing
December 2019

Supplementation With the Sialic Acid Precursor N-Acetyl-D-Mannosamine Breaks the Link Between Obesity and Hypertension.

Circulation 2019 12 10;140(24):2005-2018. Epub 2019 Oct 10.

University of Texas Southwestern Medical Center, Dallas (J.P., W.V., S.B., I.S.Y., K.T., A.S., H.C., N.C.S., A.R., K.L.C., C.M., P.W.S.).

Background: Obesity-related hypertension is a common disorder, and attempts to combat the underlying obesity are often unsuccessful. We previously revealed that mice globally deficient in the inhibitory immunoglobulin G (IgG) receptor FcγRIIB are protected from obesity-induced hypertension. However, how FcγRIIB participates is unknown. Studies were designed to determine if alterations in IgG contribute to the pathogenesis of obesity-induced hypertension.

Methods: Involvement of IgG was studied using IgG μ heavy chain-null mice deficient in mature B cells and by IgG transfer. Participation of FcγRIIB was interrogated in mice with global or endothelial cell-specific deletion of the receptor. Obesity was induced by high-fat diet (HFD), and blood pressure (BP) was measured by radiotelemetry or tail cuff. The relative sialylation of the Fc glycan on mouse IgG, which influences IgG activation of Fc receptors, was evaluated by lectin blotting. Effects of IgG on endothelial NO synthase were assessed in human aortic endothelial cells. IgG Fc glycan sialylation was interrogated in 3442 human participants by mass spectrometry, and the relationship between sialylation and BP was evaluated. Effects of normalizing IgG sialylation were determined in HFD-fed mice administered the sialic acid precursor N-acetyl-D-mannosamine (ManNAc).

Results: Mice deficient in B cells were protected from obesity-induced hypertension. Compared with IgG from control chow-fed mice, IgG from HFD-fed mice was hyposialylated, and it raised BP when transferred to recipients lacking IgG; the hypertensive response was absent if recipients were FcγRIIB-deficient. Neuraminidase-treated IgG lacking the Fc glycan terminal sialic acid also raised BP. In cultured endothelial cells, via FcγRIIB, IgG from HFD-fed mice and neuraminidase-treated IgG inhibited vascular endothelial growth factor activation of endothelial NO synthase by altering endothelial NO synthase phosphorylation. In humans, obesity was associated with lower IgG sialylation, and systolic BP was inversely related to IgG sialylation. Mice deficient in FcγRIIB in endothelium were protected from obesity-induced hypertension. Furthermore, in HFD-fed mice, ManNAc normalized IgG sialylation and prevented obesity-induced hypertension.

Conclusions: Hyposialylated IgG and FcγRIIB in endothelium are critically involved in obesity-induced hypertension in mice, and supportive evidence was obtained in humans. Interventions targeting these mechanisms, such as ManNAc supplementation, may provide novel means to break the link between obesity and hypertension.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027951PMC
December 2019

Superiority of Out-of-Office Blood Pressure for Predicting Hypertensive Heart Disease in Non-Hispanic Black Adults.

Hypertension 2019 11 16;74(5):1192-1199. Epub 2019 Sep 16.

From the Smidt Heart Institute, Hypertension Center of Excellence (F.R., R.G.V.), Cedars-Sinai Medical Center, Los Angeles, CA.

Black Americans suffer disproportionately from hypertension and hypertensive heart disease. Out-of-office blood pressure (BP) is more predictive for cardiovascular complications than clinic BP; however, the relative abilities of clinic and out-of-office BP to predict left ventricular hypertrophy in black and white adults have not been established. Thus, we aimed to compare associations of out-of-office and clinic BP measurement with left ventricular hypertrophy by cardiac magnetic resonance imaging among non-Hispanic black and white adults. In this cross-sectional study, 1262 black and 927 white participants of the Dallas Heart Study ages 30 to 64 years underwent assessment of standardized clinic and out-of-office (research staff-obtained) BP and left ventricular mass index. In multivariable-adjusted analyses of treated and untreated participants, out-of-office BP was a stronger determinant of left ventricular hypertrophy than clinic BP (odds ratio per 10 mm Hg, 1.48; 95% CI, 1.34-1.64 for out-of-office systolic BP and 1.15 [1.04-1.28] for clinic systolic BP; 1.71 [1.43-2.05] for out-of-office diastolic BP, and 1.03 [0.86-1.24] for clinic diastolic BP). Non-Hispanic black race/ethnicity, treatment status, and lower left ventricular ejection fraction were also independent determinants of hypertrophy. Among treated Blacks, the differential association between out-of-office and clinic BP with hypertrophy was more pronounced than in treated white or untreated participants. In conclusion, protocol-driven supervised out-of-office BP monitoring provides important information that cannot be gleaned from clinic BP assessment alone. Our results underscore the importance of hypertension management programs outside the medical office to prevent hypertensive heart disease, especially in high-risk black adults. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00344903.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785391PMC
November 2019

Insulin potentiates the response to mechanical stimuli in small dorsal root ganglion neurons and thin fibre muscle afferents in vitro.

J Physiol 2019 10 1;597(20):5049-5062. Epub 2019 Oct 1.

Departments of Health Care Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Key Points: Insulin is known to activate the sympathetic nervous system centrally. A mechanical stimulus to tissues activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion neurons of these afferents. In the present study, we report the novel finding that insulin augments the mechanical responsiveness of thin fibre afferents not only at dorsal root ganglion, but also at muscle tissue levels. Our data suggest that sympathoexcitation is mediated via the insulin-induced mechanical sensitization peripherally. The present study proposes a novel physiological role of insulin in the regulation of mechanical sensitivity in somatosensory thin fibre afferents.

Abstract: Insulin activates the sympathetic nervous system, although the mechanism underlying insulin-induced sympathoexcitation remains to be determined. A mechanical stimulus to tissues such as skin and/or skeletal muscle, no matter whether the stimulation is noxious or not, activates the sympathetic nervous system via thin fibre afferents. Evidence suggests that insulin modulates putative mechanosensitive channels in the dorsal root ganglion (DRG) neurons of these afferents. Accordingly, we investigated whether insulin augments whole-cell current responses to mechanical stimuli in small DRG neurons of normal healthy mice. We performed whole-cell patch clamp recordings using cultured DRG neurons and observed mechanically-activated (MA) currents induced by mechanical stimuli applied to the cell surface. Local application of vehicle solution did not change MA currents or mechanical threshold in cultured DRG neurons. Insulin (500 mU mL ) significantly augmented the amplitude of MA currents (P < 0.05) and decreased the mechanical threshold (P < 0.05). Importantly, pretreatment with the insulin receptor antagonist, GSK1838705, significantly suppressed the insulin-induced potentiation of the mechanical response. We further examined the impact of insulin on thin fibre muscle afferent activity in response to mechanical stimuli in normal healthy rats in vitro. Using a muscle-nerve preparation, we recorded single group IV fibre activity to a ramp-shaped mechanical stimulation. Insulin significantly decreased mechanical threshold (P < 0.05), although it did not significantly increase the response magnitude to the mechanical stimulus. In conclusion, these data suggest that insulin augments the mechanical responsiveness of small DRG neurons and potentially sensitizes group IV afferents to mechanical stimuli at the muscle tissue level, possibly contributing to insulin-induced sympathoexcitation.
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http://dx.doi.org/10.1113/JP278527DOI Listing
October 2019

Emergence of Home Blood Pressure-Guided Management of Hypertension Based on Global Evidence.

Hypertension 2019 Jul 1:HYPERTENSIONAHA11912630. Epub 2019 Jul 1.

Hypertension Center STRIDE-7, School of Medicine, Third Department of Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, Greece (A.K., G.S.S.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635060PMC
July 2019

Exaggerated pressor and sympathetic responses to stimulation of the mesencephalic locomotor region and exercise pressor reflex in type 2 diabetic rats.

Am J Physiol Regul Integr Comp Physiol 2019 08 15;317(2):R270-R279. Epub 2019 May 15.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.

The cardiovascular responses to exercise are potentiated in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanisms causing this abnormality remain unknown. Central command (CC) and the exercise pressor reflex (EPR) are known to contribute significantly to cardiovascular control during exercise. Thus these neural signals are viable candidates for the generation of the abnormal circulatory regulation in this disease. We hypothesized that augmentations in CC as well as EPR function contribute to the heightened cardiovascular responses during exercise in T2DM. To test this hypothesis, changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to electrical stimulation of mesencephalic locomotor region (MLR), a putative component of the central command pathway, and activation of the EPR, evoked by electrically induced hindlimb muscle contraction, were examined in decerebrate animals. Sprague-Dawley rats were given either a normal diet (control) or a high-fat diet (14-16 wk) in combination with two low doses (35 mg/kg , 25 mg/kg ) of streptozotocin (T2DM). The changes in MAP and RSNA responses to MLR stimulation were significantly greater in T2DM compared with control (2,739 ± 123 vs. 1,298 ± 371 mmHg/s, 6,326 ± 1,621 vs. 1,390 ± 277%/s, respectively, < 0.05). Similarly, pressor and sympathetic responses to activation of the EPR in diabetic animals were significantly augmented compared with control animals (436 ± 74 vs. 134 ± 44 mmHg/s, 645 ± 135 vs. 139 ± 65%/s, respectively, < 0.05). These findings provide the first evidence that CC and the EPR may generate the exaggerated rise in sympathetic activity and blood pressure during exercise in T2DM.
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http://dx.doi.org/10.1152/ajpregu.00061.2019DOI Listing
August 2019

Prevalence of Apparent Treatment-Resistant Hypertension in the United States According to the 2017 High Blood Pressure Guideline.

Mayo Clin Proc 2019 05;94(5):776-782

Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas. Electronic address:

Objective: To evaluate the prevalence of apparent treatment-resistant hypertension (aTR-hypertension) in US adults with treated hypertension by using the nationally representative National Health and Nutrition Examination Survey (NHANES).

Patients And Methods: Nonpregnant US adults older than 20 years with a self-reported history of treated hypertension who had blood pressure measured in NHANES cycles 2007 to 2014 were included in this study. Study participants were stratified into 4 groups according to average blood pressure and antihypertensive medication use: well-controlled hypertension, undertreated hypertension, aTR-hypertension by the 2017 guideline, and aTR-hypertension by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guideline. National Health and Nutrition Examination Survey sample weights were used to estimate the national prevalence.

Results: From 2007 to 2014, 5512 participants with treated hypertension representing 46.7 million people nationally were included. Compared with JNC 7 guideline criteria, application of the 2017 high blood pressure guideline criteria increased the prevalence of aTR-hypertension in US adults with treated hypertension from 12.0% to 15.95%, identifying an additional 1.85 million individuals with aTR-hypertension nationally. Individuals newly reclassified as having aTR-hypertension were younger. However, the prevalence of thiazide diuretic use remained less than 70%, and that of mineralocorticoid antagonist use remained less than 10% regardless of the guideline definition.

Conclusion: On the basis of the 2017 high blood pressure guideline, the prevalence of aTR-hypertension is 15.95% in US adults with treated hypertension. This represents an absolute increase of 4% (1.85 million additional individuals nationally) compared with the JNC 7 guideline definition, with a consistent increase across all subpopulations with treated hypertension.
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http://dx.doi.org/10.1016/j.mayocp.2018.12.033DOI Listing
May 2019

Usefulness of Blood Pressure Variability Indices Derived From 24-Hour Ambulatory Blood Pressure Monitoring in Detecting Autonomic Failure.

J Am Heart Assoc 2019 04;8(7):e010161

1 Hypertension Section University of Texas Southwestern Medical Center Dallas TX.

Background Increased blood pressure ( BP ) variability and nondipping status seen on 24-hour ambulatory BP monitoring are often observed in autonomic failure ( ATF ). Methods and Results We assessed BP variability and nocturnal BP dipping in 273 patients undergoing ambulatory BP monitoring at Southwestern Medical Center between 2010 and 2017. SD , average real variability, and variation independent of mean were calculated from ambulatory BP monitoring. Patients were divided into a discovery cohort (n=201) and a validation cohort (n=72). ATF was confirmed by formal autonomic function test. In the discovery cohort, 24-hour and nighttime average real variability, SD , and variation independent of mean did not differ significantly between ATF (n=25) and controls (n=176, all P>0.05). However, daytime SD, daytime coefficient of variation, and daytime variation independent of mean of systolic BP ( SBP ) were all significantly higher in patients with ATF than in controls in both discovery and validation cohorts. Nocturnal BP dipping was more blunted in ATF patients than controls in both cohorts (both P<0.01). Using the threshold of 16 mm Hg, daytime SD SBP yielded a sensitivity of 77% and specificity of 82% in detecting ATF in the validation cohort, whereas nondipping status had a sensitivity of 80% and specificity of 44%. The area under the receiver operator characteristic of daytime SD SBP was greater than the area under the receiver operator characteristic of nocturnal SBP dipping (0.79 [0.66-0.91] versus 0.73 [0.58-0.87], respectively). Conclusions Daytime SD of SBP is a better screening tool than nondipping status in detecting autonomic dysfunction.
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http://dx.doi.org/10.1161/JAHA.118.010161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509738PMC
April 2019

Phosphate, the forgotten mineral in hypertension.

Curr Opin Nephrol Hypertens 2019 07;28(4):345-351

Hypertension Section.

Purpose Of Review: The purpose of this study is to review the current literature related to the role of inorganic phosphate in the pathogenesis of hypertension.

Recent Findings: An increasing number of publications have revealed a detrimental role of inorganic phosphate, which is commonly used as a flavor enhancer or preservative in the processed food, in promoting hypertension in otherwise healthy individuals. Animal experimental data indicate that dietary phosphate excess engages multiple mechanisms that promote hypertension, including overactivation of the sympathetic nervous system, increased vascular stiffness, impaired endothelium-dependent vasodilation, as well as increased renal sodium absorption or renal injury. These effects may be explained by direct effects of high extracellular phosphate levels or increase in phosphaturic hormones such as fibroblast growth factor 23, or downregulation of klotho, a transmembrane protein expressed in multiple organs which possess antiaging property.

Summary: Dietary phosphate, particularly inorganic phosphate, is an emerging risk factor for hypertension which is ubiquitous in the western diet. Large randomized clinical trials are needed to determine if lowering dietary phosphate content constitutes an effective nonpharmacologic intervention for prevention and treatment of hypertension.
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http://dx.doi.org/10.1097/MNH.0000000000000503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692179PMC
July 2019

Rationale and methods for a multicenter clinical trial assessing exercise and intensive vascular risk reduction in preventing dementia (rrAD Study).

Contemp Clin Trials 2019 04 1;79:44-54. Epub 2019 Mar 1.

Institute for Dementia Research and Prevention, Pennington Biomedical Research Center, Baton Rouge, LA, USA. Electronic address:

Alzheimer's Disease (AD) is an age-related disease with modifiable risk factors such as hypertension, hypercholesterolemia, obesity, and physical inactivity influencing the onset and progression. There is however, no direct evidence that reducing these risk factors prevents or slows AD. The Risk Reduction for Alzheimer's Disease (rrAD) trial is designed to study the independent and combined effects of intensive pharmacological control of blood pressure and cholesterol and exercise training on neurocognitive function. Six hundred and forty cognitively normal older adults age 60 to 85 years with hypertension and increased risk for dementia will be enrolled. Participants are randomized into one of four intervention group for two years: usual care, Intensive Reduction of Vascular Risk factors (IRVR) with blood pressure and cholesterol reduction, exercise training (EX), and IRVR+EX. Neurocognitive function is measured at baseline, 6, 12, 18, and 24 months; brain MRIs are obtained at baseline and 24 months. We hypothesize that both IRVR and EX will improve global cognitive function, while IRVR+EX will provide a greater benefit than either IRVR or EX alone. We also hypothesize that IRVR and EX will slow brain atrophy, improve brain structural and functional connectivity, and improve brain perfusion. Finally, we will explore the mechanisms by which study interventions impact neurocognition and brain. If rrAD interventions are shown to be safe, practical, and successful, our study will have a significant impact on reducing the risks of AD in older adults. NCT Registration: NCT02913664.
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http://dx.doi.org/10.1016/j.cct.2019.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436980PMC
April 2019

High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice.

Circulation 2019 03;139(11):1422-1434

Department of Internal Medicine, Hypertension Section (P.P.-O., H.K.K., W.V.), University of Texas Southwestern Medical Center, Dallas.

Background: Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown whether dietary Pi excess contributes to exercise intolerance and physical inactivity.

Methods: To determine an association between Pi excess and physical activity in humans, we assessed the relationship between serum Pi and actigraphy-determined physical activity level, as well as left ventricular function by cardiac magnetic resonance imaging, in DHS-2 (Dallas Heart Study phase 2) participants after adjusting for relevant variables. To determine direct effects of dietary Pi on exercise capacity, oxygen uptake, serum nonesterified fatty acid, and glucose were measured during exercise treadmill test in C57/BL6 mice fed either a high-Pi (2%) or normal-Pi (0.6%) diet for 12 weeks. To determine the direct effect of Pi on muscle metabolism and expression of genes involved in fatty acid metabolism, additional studies in differentiated C2C12 myotubes were conducted after subjecting to media containing 1 to 3 mmol/L Pi (pH 7.0) to simulate in vivo phosphate conditions.

Results: In participants of the DHS-2 (n=1603), higher serum Pi was independently associated with reduced time spent in moderate to vigorous physical activity ( P=0.01) and increased sedentary time ( P=0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared with the control diet, consumption of high-Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, and fatty acid levels and led to downregulation of genes involved in fatty acid synthesis, release, and oxidation, including Fabp4, Hsl, Fasn, and Pparγ, in muscle. Similar results were recapitulated in vitro by incubating C2C12 myotubes with high-Pi media.

Conclusions: Our data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle fatty acid metabolism and exercise capacity that is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.037550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411426PMC
March 2019

Diagnostic Thresholds for Blood Pressure Measured at Home in the Context of the 2017 Hypertension Guideline.

Hypertension 2018 12;72(6):1312-1319

Division of Cardiology (W.V., C.A., S.R.D., J.D.B., A.K., J.A.d.L.), University of Texas Southwestern Medical Center, Dallas.

Most guidelines have recommended lower home blood pressure (BP) threshold when clinic BP threshold of 140/90 mm Hg is used for diagnosis of hypertension. However, home BP thresholds to define hypertension have never been determined in the general population in the United States. We identified home BP thresholds for stage 1 (BP ≥130/80 mm Hg) hypertension using a regression-based approach in the DHS (Dallas Heart Study; n=5768) and the NCMH study (North Carolina Masked Hypertension; n=420). Home BP thresholds were also assessed using outcome-derived approach based on the composite of all-cause mortality or cardiovascular events in the DHS cohort. For this approach, BP thresholds were identified only for systolic BP because diastolic BP was not associated with the outcome. Among untreated participants, the regression-derived thresholds for home BP corresponding to clinic BP for stage 1 hypertension were 129/80 mm Hg in blacks, 130/80 mm Hg in whites, and 126/78 mm Hg in Hispanics, respectively. The results are similar in the North Carolina cohort. The 11-year composite cardiovascular and mortality events corresponding to clinic systolic BP >130 mm Hg were higher in blacks than in whites and Hispanics (13.3% versus 5.98% versus 5.52%, respectively). Using a race/ethnicity-specific composite outcome in the untreated DHS participants, the outcome-derived home systolic BP thresholds corresponding to stage 1 hypertension were 130 mm Hg in blacks, 129 mm Hg in whites, and 131 mm Hg in Hispanics, respectively. Our data based on both regression-derived and outcome approach support home BP threshold of 130/80 mm Hg for diagnosis of hypertension in blacks, whites, and Hispanics.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309342PMC
December 2018

Prognostic Value of Masked Uncontrolled Hypertension.

Hypertension 2018 10;72(4):862-869

Department of Cardiovascular Sciences, University of Leuven, Belgium (L.T., J.A.S.).

The prognostic relevance of masked uncontrolled hypertension (MUCH) is incompletely clear, and its global impact on cardiovascular outcomes and mortality has not been assessed. The aim of this study was to perform a meta-analysis on the prognostic value of MUCH. We searched for articles assessing outcome in patients with MUCH compared with those with controlled hypertension (CH) and reporting adjusted hazard ratio and 95% CI. We identified 6 studies using ambulatory blood pressure monitoring (12 610 patients with 933 events) and 5 using home blood pressure measurement (17 742 patients with 394 events). The global population included 30 352 patients who experienced 1327 events. Selected studies had cardiovascular outcomes and all-cause mortality as primary outcome, and the main result is a composite of these events. The overall adjusted hazard ratio was 1.80 (95% CI, 1.57-2.06) for MUCH versus CH. Subgroup meta-analysis showed that adjusted hazard ratio was 1.83 (95% CI, 1.52-2.21) in studies using ambulatory blood pressure monitoring and 1.75 (95% CI, 1.38-2.20) in those using home blood pressure measurement. Risk was significantly higher in MUCH than in CH independently of follow-up length and types of studied events. MUCH was at significantly higher risk than CH in all ethnic groups, but the highest hazard ratio was found in studies, including black patients. Risk of cardiovascular events and all-cause mortality is significantly higher in patients with MUCH than in those with CH. MUCH detected by ambulatory or home blood pressure measurement seems to convey similar prognostic information.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.118.11499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205750PMC
October 2018

Accurate Blood Pressure in the Office.

Circulation 2018 10;138(17):1771-1773

Hypertension Section, Cardiology Division, University of Texas Southwestern Medical Center, Dallas.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363479PMC
October 2018

Antinuclear antibodies in the general population: positive association with inflammatory and vascular biomarkers but not traditional cardiovascular risk factors.

Clin Exp Rheumatol 2018 Nov-Dec;36(6):1031-1037. Epub 2018 Sep 17.

Division of Cardiology, University of Texas Southwestern, Dallas, TX, USA.

Objectives: Patients with clinically evident autoimmune disease are at increased risk for premature cardiovascular disease (CVD). Markers of serological autoimmunity such as anti-nuclear antibodies (ANA) are found in approximately 25% of the general population. Yet, the vast majority will not develop clinical autoimmune disease. Serological autoimmunity is a risk factor for CVD death in individuals without autoimmune disease; however, the mechanisms mediating this excess CVD risk have not been elucidated.

Methods: We examined associations of ANA with traditional cardiovascular risk factors, inflammatory mediators, and vascular biomarkers in the Dallas Heart Study - a large, representative multiethnic population-based cohort. Plasma ANA were measured by enzyme linked immunosorbent assay in 3,488 Dallas Heart Study participants aged 30 to 65 years who do not have known rheumatologic disease. Associations of ANA with demographic characteristics, cardiovascular risk factors, and biomarkers were assessed using univariable and multivariable linear regression.

Results: Factors independently associated with higher ANA include female sex, African-American race/ethnicity, soluble intracellular adhesion molecule-1, soluble CD40 ligand, chemokine CXCL-2, and Cystatin C (p<0.05 for each). ANA was not associated with traditional cardiovascular risk factors, high sensitivity C-reactive protein, coronary artery calcium scores, or aortic wall thickness.

Conclusion: ANA are associated with inflammatory mediators and biomarkers of vascular activation, but not with traditional cardiovascular risk factors in a multiethnic population-based cohort. These findings suggest that the cardiovascular risk associated with ANA may involve pathways distinct from traditional risk factors and include dysregulation of endothelial cells and the immune system.
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March 2019

Augmented venoarteriolar response with ageing is associated with morning blood pressure surge.

Exp Physiol 2018 11 5;103(11):1448-1455. Epub 2018 Sep 5.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital Dallas, Dallas, TX, USA.

New Findings: What is the central question of this study? The venoarteriolar response (VAR) contributes substantially to the maintenance of orthostatic tolerance in humans. Despite its importance in haemodynamic homeostasis, the impact of ageing on the VAR remains understudied. What is the main finding and its importance? Older adults exhibit an augmented VAR in response to leg dependency. The age-related augmentation of the VAR might be linked with progressive increases of peripheral vascular resistance with ageing. We found a modest but significant correlation between the leg VAR and the morning blood pressure surge in older adults. Augmented leg VAR might contribute to the blood pressure elevation in the early morning.

Abstract: The venoarteriolar response (VAR) is a non-adrenergic, non-baroreflex-mediated mechanism of vasoconstriction, which has been proposed to contribute ∼45% of the increase in total peripheral resistance during orthostasis. Despite its importance in human cardiovascular control during orthostatic stress, there is no information available regarding the impact of age and sex on the VAR or its role in diurnal blood pressure (BP) variation. We studied 33 (15 women) young (mean ± SD; 28 ± 4 years old) and 26 (12 women) older (71 ± 3 years old) healthy individuals. Brachial and femoral blood flow were measured using Doppler ultrasound. The percentage reduction in vascular conductance (blood flow/mean BP) during 4 min of limb dependency (35-40 cm below the heart level) was used to assess the VAR. The morning surge in BP was assessed using 24 h ambulatory BP monitoring. Peak VAR in the lower limb, but not in the upper limb, was significantly higher in the older than the younger adults (33 ± 4 versus 26 ± 6%, older versus young; P < 0.05). There was no sex difference in the VAR in either the young or the older group. A greater leg VAR was related to a greater morning surge in BP in older adults (r = -0.4, P = 0.02) but not in the young adults (r = -0.26, P = 0.1). Thus, advancing age enhances the VAR in the lower limb and is associated with the morning blood pressure surge in older adults. Sex does not affect this local axonal reflex in healthy humans.
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http://dx.doi.org/10.1113/EP087166DOI Listing
November 2018

Usefulness of a Simple Algorithm to Identify Hypertensive Patients Who Benefit from Intensive Blood Pressure Lowering.

Am J Cardiol 2018 07 11;122(2):248-254. Epub 2018 Apr 11.

Quantitative Biomedical Research Center, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address:

Large randomized trials have provided inconsistent evidence regarding the benefit of intensive blood pressure (BP) lowering in hypertensive patients. Identifying which patients derive a higher net benefit is essential in informing clinical decision-making. We used patient-level data from 2 trials that tested intensive versus standard BP lowering, Systolic Blood Pressure Intervention Trial (SPRINT) and Action to Control Cardiovascular Risk in Diabetes (ACCORD), to assess whether stratification by cardiovascular disease (CVD) risk will identify patients with a more favorable risk-benefit profile for intensive BP lowering. Within SPRINT, we selected a subset of patients at the extremes of major adverse cardiovascular event rates to develop a decision tree using recursive partitioning modeling. We then validated its predictive effects in the remaining 'intermediate' SPRINT subset (n = 8,357) and externally in ACCORD (n = 2,258). Recursive partitioning produced a 3-variable decision tree model consisting of age ≥74 years, urinary albumin-creatinine ratio ≥34, and history of clinical CVD. It classified 48.6% of SPRINT and 55.3% of ACCORD patients as "high-risk." Compared with standard treatment, intensive BP lowering was associated with lower rates of major adverse cardiovascular event in this high-risk population in both SPRINT cross-validation data (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.52 to 0.85) and ACCORD (HR 0.67, 95% CI 0.50 to 0.90), but not in the remaining low-risk patients (SPRINT: HR 0.83, 95% CI 0.56 to 1.25; ACCORD: HR 1.09, 95% CI 0.64 to 1.83). Additionally, intensive BP lowering did not confer an excess risk of serious adverse events in the high-risk group. In conclusion, this simple risk prediction model consisting of age, urinary albumin-creatinine ratio, and clinical CVD history successfully identified a subset of hypertensive patients who derived a more favorable risk-benefit profile for intensive BP lowering.
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http://dx.doi.org/10.1016/j.amjcard.2018.03.361DOI Listing
July 2018

Ambulatory pulse pressure, brain neuronal fiber integrity, and cerebral blood flow in older adults.

J Cereb Blood Flow Metab 2019 05 8;39(5):926-936. Epub 2017 Dec 8.

1 Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, TX, USA.

Ambulatory blood pressure (ABP) reflects the end-organ vascular stress in daily life; however, its influence on brain neuronal fiber integrity and cerebral blood flow (CBF) remains unclear. The objective of this study was to determine the associations among ABP, white matter (WM) neuronal fiber integrity, and CBF in older adults. We tested 144 participants via ABP monitoring and diffusion tensor imaging. The total level and pulsatile indices of CBF were measured by phase-contrast MRI and transcranial Doppler, respectively. Neuropsychological assessment was conducted in 72 participants. Among ambulatory and office BP measures, elevated 24-h pulse pressure (PP) was associated with the greatest number of WM skeleton voxels with decreased fractional anisotropy (FA) and increased mean diffusivity (MD). Furthermore, these associations remained significant after adjusting for age, antihypertensive use, aortic stiffness, WM lesion volume, and office PP. Radial diffusivity (RD) was elevated in the regions with decreased FA, while axial diffusivity was unaltered. The reduction in diastolic index explained a significant proportion of the individual variability in FA, MD, and RD. Executive function performance was correlated with WM fiber integrity. These findings suggest that elevated ambulatory PP may deteriorate brain neuronal fiber integrity via reduction in diastolic index.
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http://dx.doi.org/10.1177/0271678X17745027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501504PMC
May 2019