HTN Subjects Research Articles

Endothelin-1 Correlates with Blood Pressure and Pulse Pressure in Females with Lupus Associated Hypertension

Systemic Lupus Erythematosus (SLE) is a common autoimmune disease that is classified by IgG complex deposition in end organs including the kidney, heart, and vasculature. SLE disproportionally affects women to men (9:1 ratio), with a high prevalence in African American women. Importantly, patients with an SLE diagnosis have common cardiovascular complications including hypertension. Importantly, numerous studies have reported that plasma and urinary endothelin-1 (ET-1) levels are elevated in patients with SLE or hypertension. However, few studies have investigated the role of the synergistic effects of SLE and hypertension on ET-1. Therefore, we hypothesized that women with SLE and hypertension would have elevated plasma ET-1 levels compared to SLE or hypertension alone. To investigate this, we recruited non-SLE non-HTN controls (n=8), non-SLE HTN (n=7), SLE non-HTN (n=5), and SLE-HTN (n=6) female human subjects and analyzed clinical and demographic characteristics, plasma ET-1, c-reactive protein (CRP), soluble vascular adhesion molecule-1 (sVCAM-1), and anti-Smith autoantibodies. We found that plasma ET-1 levels are significantly higher in African American compared to European American patients independent of SLE or blood pressure status (p=0.0182). When plasma ET-1 levels were correlated with age and body mass index (BMI), ET-1 had a positive association with age (r=0.4861;p=0.0118), but no correlation with BMI (r=0.2137;p=0.2945). When subjects we characterized by SLE diagnosis, we found that female subjects with SLE had elevated plasma ET-1 levels compared to non-SLE controls (p=0.0141). Next, we stratified subjects by blood pressure status and found that only SLE-HTN subjects had significantly elevated plasma ET-1 levels compared to non-SLE non-HTN controls (p=0.0005), and a trend for elevated ET-1 levels over SLE non-HTN (p=0.0799). Lastly, we correlated plasma ET-1 levels to offce systolic blood pressure, diastolic blood pressure and calculated pulse pressure. We found that plasma ET-1 positively associated with systolic blood pressure (r=0.5621;p=0.0035) and pulse pressure (r=0.5810;p=0.0023) but not diastolic blood pressure (r=0.3177;p=0.1217). These data demonstrate that plasma ET-1 levels associate with SLE diagnosis and blood pressure status in our cohort of female SLE human subjects. Further investigation of ET signaling should be done in SLE and SLE-HTN human subjects. Veterans Affairs Biomedical Laboratory Research & Development Career Development Award (CDA-2) 1IK2BX005605-01 to J.P.V.B, Medical University of South Carolina College of Medicine Program Project Grant to J.C.O and J.P.V.B., and Medical University of South Carolina Core Centers for Clinical Research Project Award P30AR072582 to M.A.C and J.P.V.B. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

0599 Effects of Proximal HGN Stimulation in HTN Subjects with Moderate to Severe OSA: A 5-Year Analysis of the THN3 RCT

0599 Effects of Proximal HGN Stimulation in HTN Subjects with Moderate to Severe OSA: A 5-Year Analysis of the THN3 RCT

Utility of 24-hour ambulatory blood pressure monitoring in potential living kidney donors

IntroductionHypertension (HTN) is a risk factor for cardiovascular disease; therefore, it is imperative to risk stratify potential kidney donors during evaluation. Clinic blood pressure (CBP) measurement is inaccurate in assessing presence or absence of HTN. There is paucity of data about utility of 24-h ambulatory blood pressure monitoring (ABPM) during kidney donor evaluation.Methods24-h ABPM is performed on all kidney donors at Mayo Clinic Florida. We conducted retrospective review of 264 consecutive potential kidney donors from 1/1/2012 to 12/31/2017. Demographic, comorbid conditions, laboratory results and 24-h ABPM data were collected. Subjects were divided into two groups: Group1: Subjects with no prior history of HTN and new diagnosis of HTN using 24-h ABPM; Group 2: Subjects with no prior history of hypertension and normal BP on 24-h ABPM.ResultsBaseline demographic included mean age 46.40 years, 39% males, 78.4% Caucasians, and mean BMI was 26.94. Twenty one subjects (8.0%) had prior diagnosis of HTN. Among 243 subjects without prior HTN, 62 (25.5%) were newly diagnosed with HTN using 24-h ABPM. CBP was high only in 27 out of 62 (43.6%) of newly diagnosed HTN subjects. Thirty-five subjects (14.4%) had masked HTN and 14 subjects (5.8%) had white-coat HTN. Newly diagnosed hypertensive subjects were more likely to be males as compared to Group 2 (53.2% vs 34.3% P = 0.008). There was a trend of more non-Caucasians subjects (30.6% vs 19.9% P = 0.08) and more active smokers (17.7% vs 11.6%, P = 0.054) in Group1 as compared to Group 2. Only 17 (27.4%) out of 62 newly diagnosed hypertensive subjects were deemed suitable for kidney donation as compared to 105 (58.0%) out of 181 normotensive subjects (P < 0.001).ConclusionIn our cohort, use of ABPM resulted in new diagnosis of HTN in 1 out of 4 potential kidney donors. Newly diagnosed HTN was more common in men, those with non-Caucasian race, and in active smokers. There was a significantly reduced acceptance rate for kidney donation among newly diagnosed HTN subjects. Further studies are needed to determine the value of 24-h ABPM among these high risk groups.

Pre-hypertension and subclinical carotid damage: a meta-analysis.

The association between pre-hypertension (pre-HTN) and subclinical carotid damage is poorly defined. We performed a meta-analysis of ultrasonographic studies assessing carotid intima-media thickness (IMT) in untreated pre-HTN subjects. The OVID-MEDLINE, PubMed, and Cochrane CENTRAL databases were searched for English-language articles without time restriction up to February 2018 through focused, high sensitive search strategies. Studies were identified by crossing the following search terms: "pre-hypertension", "high normal blood pressure", "carotid intima-media thickness", "carotid atherosclerosis", "ultrasonography". Overall, 7645 subjects (3374 normotensive, 1936 untreated pre-HTN, and 2335 HTN individuals) of both genders were included in seven studies. In the pooled study population, common carotid IMT showed a progressive increase from normotensive (723 ± 39 µm) to pre-HTN (779 ± 45 µm) (standardized mean difference, SMD 0.36 ± 0.08, CI 0.34-0.46, p < 0.0001) and to HTN subjects (858 ± 82 µm) (SMD 0.39 ± 0.07, CI 0.26-0.54, p = 0.002 vs. pre-HT). The statistical difference did not change after correction for publication bias and was not affected by a single study effect. Our meta-analysis shows that carotid IMT in pre-HTN subjects is intermediate between normotensive and HTN individuals. These findings support the view that pre-HTN is an unfavourable condition that should be properly managed in order to prevent vascular damage.

Pre-hypertension and subclinical cardiac damage: A meta-analysis of echocardiographic studies

AimThe association between pre-hypertension (pre-HTN) and subclinical cardiac damage remains undefined. We performed a systematic meta-analysis of echocardiographic studies in order to provide a comprehensive information on structural and functional cardiac changes in untreated pre-HTN subjects. DesignStudies were identified by crossing the following search terms: “pre-hypertension”, “high normal blood pressure” “heart” “left ventricular hypertrophy”, “left ventricular function”, “diastolic function”, “left atrial size”, “aortic root size”, “echocardiography.” ResultsA total 73,556 subjects (44,170 normotensive, 17,314 pre-HTN, and 12,072 HTN individuals) of both genders were included in 20 studies. Left ventricular (LV) mass index and relative wall thickness (RWT) were greater in pre-HTN than in normotensives (standard means difference: 0.32 ± 0.07 and 0.30 ± 0.07, respectively, p < 0.001 for both). The E/e′ ratio (0.26 ± 0.02, p < 0.001) and left atrium (LA) diameter were higher (0.55 ± 0.02, p < 0.001) in pre-HTN than in normotensive subjects. HTN subjects showed a greater LV mass index (0.27 ± 0.03, p < 0.001), RWT (0.23 ± 0.02, p < 0.001), increased E/e′ ratio (0.38 ± 0.09, p < 0.001) as well as LA diameter (0.31 ± 0.12, p < 0.001) than pre-HTN subjects. ConclusionsOur meta-analysis suggests that alterations in cardiac structure and function in pre-HTN subjects are intermediate between normotensive and HTN individuals. These findings suggest that pre-HTN may not be a benign entity. If so, early preventive strategies may prevent preclinical cardiac damage.

MCP-1 Levels are Associated with Cardiac Remodeling but not with Resistant Hypertension.

BackgroundHypertension is a chronic, low-grade inflammation process associated with the release of cytokines and development of target organ damage. Deregulated monocyte chemoattractant protein-1 (MCP-1) levels have been associated with high blood pressure and cardiovascular complications; however, the mechanisms involved are complex and not fully understood.ObjectiveThis study aimed to compare the levels of MCP-1 in patients with resistant (RH) versus mild-to-moderate (HTN) hypertension and their association with the presence or absence of left ventricular hypertrophy (LVH) in all hypertensive subjects.MethodsWe enrolled 256 hypertensive subjects: 120 RH and 136 HTN, investigating the relationship between circulating MCP-1 levels and blood pressure, biochemical data, hematologic profile, and cardiac damage within the RH and HTN groups. Plasma MCP-1 levels were measured by ELISA and LVH was assessed by echocardiography.ResultsWe found no difference in MCP-1 levels between RH and HTN subjects. On the other hand, we encountered lower MCP-1 levels in patients with LVH (105 pg/mL [100 - 260 pg/mL] versus 136 pg/mL (100 - 200 pg/mL), p = 0.005, respectively] compared with those without LVH. A logistic regression model adjusted for body mass index (BMI), age, race, aldosterone levels, and presence of diabetes and RH demonstrated that median levels of MCP-1 (2.55 pg/mL [1.22 - 5.2 pg/mL], p = 0.01) were independently associated with LVH in the entire hypertensive population.ConclusionSince MCP-1 levels were similar in both RH and HTN subjects and decreased in hypertensive patients with existing LVH, our study suggests a possible downregulation in MCP-1 levels in hypertensive individuals with LVH, regardless of hypertension strata.

Elevated levels of GDF-15 is associated with increased angiotensin II in hypertensive patients with Type 2 diabetes.

Circulatory GDF-15, angiotensin II (Ang-II) and GDF-15 mRNA expression levels were examined in three groups, in other words, control (n = 25), Type 2 diabetes (T2DM; n = 25) and Type 2 diabetes with hypertension (T2DM_HTN; n = 36). T2DM and T2DM_HTN subjects had significantly (p < 0.05) higher GDF-15 and Ang-II levels compared with control subjects. Significant positive correlation was found between Ang-II and GDF-15 levels. GDF-15 mRNA expression from blood cells was significantly elevated in T2DM_HTN (p < 0.05) but not in T2DM subjects. GDF-15 mRNA expression was significantly elevated in Ang-II-treated (50 nM) THP-1 (p < 0.001) and H9C2 (p < 0.05) cells but not altered after high glucose treatment. Collectively, our data suggest that higher levels of GDF-15 is associated with increased Ang-II levels in diabetic patients with concurrent hypertension.

The Association of Dietary l-Arginine Intake and Serum Nitric Oxide Metabolites in Adults: A Population-Based Study.

This study was conducted to investigate whether regular dietary intake of l-arginine is associated with serum nitrate + nitrite (NOx). In this cross-sectional study, 2771 men and women, who had participated in the third examination of the Tehran Lipid and Glucose Study (2006–2008), were recruited. Demographics, anthropometrics and biochemical variables were evaluated. Dietary data were collected using a validated 168-food item semi-quantitative food frequency questionnaire and dietary intake of l-arginine was calculated. To determine any association between dietary l-arginine and serum NOx, linear regression models with adjustment for potential confounders were used. Mean age of participants (39.2% men) was 45.9 ± 15.9 years. After adjustment for all potential confounding variables, a significant positive association was observed between l-arginine intake and serum NOx concentrations in the fourth quartile of l-arginine (β = 6.63, 95% CI = 4.14, 9.12, p for trend = 0.001), an association stronger in women. Further analysis, stratified by age, body mass index and hypertension status categories, showed a greater association in middle-aged and older adults (β = 9.12, 95% CI = 3.99, 13.6 and β = 12.1, 95% CI = 6.48, 17.7, respectively). l-arginine intakes were also strongly associated with serum NOx levels in overweight and obese subjects in the upper quartile (β = 10.7, 95% CI = 5.43, 16.0 and β = 11.0, 95% CI = 4.29, 17.5); a greater association was also observed between l-arginine intakes and serum NOx in non-hypertensive (HTN) compared to HTN subjects (β = 2.65, 95% CI = 2.1–3.2 vs. β = 1.25, 95% CI = −1.64–4.15). Dietary l-arginine intakes were associated to serum NOx and this association may be affected by sex, age, body mass index, and hypertension status.

Pheochromocytoma Is Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse Myocardial Fibrosis, and Myocardial Dysfunction

BackgroundPheochromocytoma is associated with catecholamine-induced cardiac toxicity, but the extent and nature of cardiac involvement in clinical cohorts is not well-characterized. ObjectivesThis study characterized the cardiac phenotype in patients with pheochromocytoma using cardiac magnetic resonance (CMR). MethodsA total of 125 subjects were studied, including patients with newly diagnosed pheochromocytoma (n = 29), patients with previously surgically cured pheochromocytoma (n = 31), healthy control subjects (n = 51), and hypertensive control subjects (HTN) (n = 14), using CMR (1.5-T) cine, strain imaging by myocardial tagging, late gadolinium enhancement, and native T1 mapping (Shortened Modified Look-Locker Inversion recovery [ShMOLLI]). ResultsPatients who were newly diagnosed with pheochromocytoma, compared with healthy and HTN control subjects, had impaired left ventricular (LV) ejection fraction (<56% in 38% of patients), peak systolic circumferential strain (p < 0.05), and diastolic strain rate (p < 0.05). They had higher myocardial T1 (974 ± 25 ms, as compared with 954 ± 16 ms in healthy and 958 ± 23 ms in HTN subjects; p < 0.05), areas of myocarditis (median 22% LV with T1 >990 ms, as compared with 1% in healthy and 2% in HTN subjects; p < 0.05), and focal fibrosis (59% had nonischemic late gadolinium enhancement, as compared with 14% in HTN subjects). Post-operatively, impaired LV ejection fraction typically normalized, but systolic and diastolic strain impairment persisted. Focal fibrosis (median 5% LV) and T1 abnormalities (median 12% LV) remained, the latter of which may suggest some diffuse fibrosis. Previously cured patients demonstrated abnormal diastolic strain rate (p < 0.001), myocardial T1 (median 12% LV), and small areas of focal fibrosis (median 1% LV). LV mass index was increased in HTN compared with healthy control subjects (p < 0.05), but not in the 2 pheochromocytoma groups. ConclusionsThis first systematic CMR study characterizing the cardiac phenotype in pheochromocytoma showed that cardiac involvement was frequent and, for some variables, persisted after curative surgery. These effects surpass those of hypertensive heart disease alone, supporting a direct role of catecholamine toxicity that may produce subtle but long-lasting myocardial alterations.

Intensity of cardiovascular and behavioral risk factors in masked and stable arterial hypertension in young subjects

Objective. To study the intensity of cardiovascular behavioral and other risk factors of masked arterial hypertension (MHTN) and stable arterial hypertension (SHTN) in young subjects (students of medical university). Design and methods . A full-design screening study included 423 young men and women aged 20–27, mean age 22, 59 % were women and 41 % — men. All subjects underwent clinical examination: physical examination — height, weight, body mass index (BMI), waist and hip circumferences, questionnaires to assess behavioral risk factors and history of the complaints; laboratory and instrumental screening: fasting serum creatinine, lipid profile (total cholesterol, triglycerides, high density lipoproteins, low density lipoproteins), 30‑second breath-hold test, standard 12‑lead electrocardiography (ECG); echocardiography and 24‑hour blood pressure monitoring in HTN subjects (with MHTN and SHTN). Results. MHTN was detected in 12,3 % subjects, SHTN — in 9 %; 78,7 % were normotensives. Subjects with SHTN were overweight — BMI 28,4 (27,4; 29,7) kg/m 2. In MHTN subjects, waist and circumferences tended to increase: 77,2 (65,1; 82) and 98 (93,2; 104) cm, respectively. MHTN patients demonstrated higher office systolic blood pressure as compared to normotensives: 120 (110; 130) versus 108,5 (100; 118) mm Hg. However, they had lower BP compared to subjects with SHTN — 139 (132,3; 140) mm Hg. Family history of early cardiovascular diseases was detected in all MHTN patients (100 %), as well as in 50 % SHTN individuals and in 56 % normotensives. The highest prevalence of behavioral risk factors was found in a group of subjects with MHTN, as compared to those with SHTN and normotensives. Conclusions . Subjects with MHTN and SHTN have prevalent indicators of behavioral and other risk factors for HTN, which form its phenotype. The development of MHTN and SHTN in young subjects is associated with the severity of clinical, genetic and behavioral risk factors.

Improved detection of elevated blood pressure in children with T2DM after implementation of EMR BP percentile smartphrase

We analyzed data from an ongoing multicenter study of cognition in primary HTN. As part of this study, matched normotensive controls had baseline ABPM to confirm normotension. Subjects were required to have both ambulatory mean SBP and DBP < 95 ile and 24 hr SBP and DBP load < 25% to be enrolled as controls. After 1 year, all subjects had repeat ABPM, thereby allowing comparison to baseline. To date, 28 control subjects have completed both baseline and 1 year ABPM. By design, all control subjects had ambulatory normotension (mean daytime SBP index, 0.89 0.05, daytime DBP index, 0.81 0.06, 24 hr SBP load, 7 7.4%) at baseline. Due to matching with the HTN subjects, 61% of controls were obese and 82% male. After 1 year, no control subject developed ambulatory HTN or diastolic preHTN. However, 8 (29%) developed ambulatory systolic preHTN (Figure). Compared with subjects who remained normotensive, those who developed systolic preHTN were more obese (BMI %ile, 97 vs. 88 %ile, p 1⁄4 0.03) and tended toward a higher 24 hr SBP load (11 vs. 5%, p 1⁄4 0.08) at baseline but were similar in age (15.8 vs. 15y, p 1⁄4 0.35), sex (% male, 87 vs 80%, p 1⁄4 0.99) and race (African American, 15 vs. 12%, p 1⁄4 0.78). Seven of 17 (41%) of subjects who were obese at baseline developed systolic preHTN. There was a trend toward greater weight gain over the year in the subjects who progressed to systolic preHTN (9.1 vs. 3.3 kg, p 1⁄4 0.09). These preliminary results suggest that progression from normotension to ambulatory preHTN is common and that obese youth are at particular risk for progression.

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study

BackgroundHypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India.Methods6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study.ResultsHTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status.ConclusionsHTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health.

Left Ventricular Hypertrophy, Diastolic Dysfunction, Pulse Pressure, and Plasma ET-1 in Marathon Runners With Exaggerated Blood Pressure Response

This study was conducted to study left ventricular hypertrophy (LVH), diastolic dysfunction, pulse pressure (PP), and plasma endothelin (ET)-1 level in amateur marathon runners with an exaggerated blood pressure response (EBPR) to exercise. The study participants included normotensive marathon runners (NM, n = 15), EBPR marathon runners (EBPR, n = 17), normotensive sedentary individuals (CON, n = 13), and hypertensive patients (HTN, n = 14). An integrated M-mode/2-dimensional echocardiographic analysis was performed. Plasma ET-1 levels at resting were measured using a commercial ELISA kit. LV wall thickness and end-diastolic dimensions as well as LV mass index (LVMI) were higher in EBPR than in CON. There were no differences in systolic function among the groups. Analysis of diastolic function, such as lower Em and higher E/Em ratio on TDI, showed a worse relaxation pattern in EBPR. Despite LVH, NM subjects showed no abnormality of LV diastolic dysfunction. HTN subjects in the early stage of their disease showed a slightly modified LV structural and diastolic function, but there was no statistical difference compared with CON. The E/Em ratio was significantly correlated with PP and LVMI. LVMI was significantly correlated with PP. There was a significant difference in plasma ET-1 concentration between marathon runners and hypertensive subjects. We demonstrated that marathon runners with EBPR showed an increase in LVMI and diastolic dysfunction more than HTN subjects in the early stage. PP was significantly related to these two variables. Caution should be exercised when connecting LVH and diastolic dysfunction with plasma ET-1 concentration in all marathon runners.

High-circulating leptin levels are associated with increased blood pressure in uncontrolled resistant hypertension

Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml(-1), respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl(-1), respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r(2)=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

The Impact of Extra Cardiac Comorbidities on Pressure Volume Relations in Heart Failure and Preserved Ejection Fraction

Background Extracardiac comorbidities are common in patients with heart failure and a preserved ejection fraction (HFPEF). We sought to evaluate the relationship between comorbidities and ventricular structure and function in patients with HFPEF through evaluation of pressure-volume analysis. Methods and Results Two hundred twenty Chinese patients with a preserved ejection fraction who were either healthy (n = 75), hypertensive without heart failure (HTN; n = 89), or hypertensive with HFPEF (HFPEF; n = 56) were studied. Using echocardiographic measures, estimated end-systolic and end-diastolic pressure-volume relationships, and the area between them as a function of EDP, the isovolumic pressure-volume areas (PVA iso), were calculated. Ventricular capacitance, as measured by V 30, was larger in patients with HFPEF compared with normal control subjects and tended to be larger compared with hypertensive control subjects. The presence of diabetes and renal insufficiency was independently associated with greater ventricular capacitance in patients with HFPEF. The PVA iso was increased in patients with HFPEF compared with HTN and normal control subjects, and in particular, it was increased in HFPEF patients with multiple comorbidities. Conclusions The presence of comorbid conditions is associated with altered pressure-volume relations and enhanced pump function in subjects with HFPEF, supporting an important role for extracardiac comorbidities in the pathophysiology of patients with this condition.

Altered cellular magnesium responsiveness to hyperglycemia in hypertensive subjects.

Previous studies by our group have identified ionic aspects of insulin resistance in hypertension, in which cellular responses to insulin were influenced by the basal intracellular ionic environment-the lower the cytosolic free magnesium (Mg(i)), the less Mg(i) increased following insulin stimulation. To investigate whether this ionic insulin resistance represents a more general abnormality of cellular responsiveness in hypertension, we studied Mg(i) responses to nonhormonal signals such as hyperglycemia (15 mmol/L) and used (31)P-nuclear magnetic resonance (NMR) spectroscopy to measure Mg(i) in erythrocytes from normal (NL, n=14) and hypertensive (HTN, n=12) subjects before and 30, 60, 120, and 180 minutes after in vitro glucose incubations. Basal Mg(i) levels were significantly lower in HTN subjects than in NL subjects (169+/-10 versus 205+/-8 micromol.L(-1), P<0.01). In NL cells, hyperglycemia significantly lowered Mg(i), from 205+/-8 micromol.L(-1) (basal, T=0) to 181+/-8, 162+/-6, 152+/-7, and 175+/-9 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P<0.005 versus T=0 at all times). In HTN cells, maximal Mg(i) responses to hyperglycemia were blunted, from 169+/-10 micromol.L(-1) (basal, T=0) to 170+/-11, 179+/-12, 181+/-14, and 173+/-15 micromol.L(-1) (T=30, 60, 120, and 180, respectively; P=NS versus T=0 at all times). For all subjects, Mg(i) responses to hyperglycemia were closely related to basal Mg(i) levels: the higher the Mg(i), the greater the response (n=26, r=0.620, P<0.001). Thus, (1) erythrocytes from hypertensive vis-à-vis normotensive subjects are resistant to the ionic effects of extracellular hyperglycemia on Mg(i) levels, and (2) cellular ionic responses to glucose depend on the basal Mg(i) environment. Altogether, these data support a role for altered extracellular glucose levels in regulating cellular magnesium metabolism and also suggest the importance of ionic factors in determining cellular responsiveness to nonhormonal as well as hormonal signals.