Impact of therapeutic lifestyle changes in resistant hypertension.

Hypertensive individuals are at an increased risk of developing heart disease and stroke. Adopting healthy lifestyles, such as being active on ≥4 days per week, weight-loss in the presence of obesity, consuming a diet rich in fruits and vegetables, and sodium below the recommended threshold, avoiding high alcohol consumption and refraining from smoking have been effective lifestyle therapies to prevent or control stage 1 hypertension (HTN). Among the 1 in 3 Americans who have HTN (systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg), 16% are diagnosed with resistant HTN (RHT). Although there are comparatively fewer studies examining the blood pressure lowering effects of therapeutic lifestyle interventions in patients with resistant HTN, the available literature appears promising. This paper reviews key studies that quantify the blood pressure lowering effects of certain therapeutic lifestyles in patients with RHT and highlights areas needing more attention.

Phosphatidylethanol Levels Are Elevated and Correlate Strongly with AUDIT Scores in Young Adult Binge Drinkers.

AIMS: To compare levels of phosphatidylethanol (PEth) to self-reported alcohol intake among young adult binge drinkers (18-30 years). METHODS: Abstainers (n = 23), moderate (n = 22), and binge drinkers (n = 58) completed an alcohol consumption questionnaire and the AUDIT. PEth was measured in whole blood and dried blood spots via high-performance liquid chromatography with tandem mass spectrometry. Also measured was mean corpuscular volume (MCV) and gamma glutamyl transpeptidase (GGT). RESULTS: Most subjects were female (65%) and Caucasian (73%). Among binge drinkers, past-month average number of binge episodes was 7.2 ± 4; average duration of binge drinking behavior was 4.3 ± 3 years. AUDIT scores and PEth levels (ng/ml) in whole blood or dried blood spots were significantly (P < 0.001) greater in binge drinkers (13 ± 4, 186 ± 170, and 65 ± 53, respectively) compared to moderate drinkers (6 ± 3, 24 ± 29, and 11 ± 13, respectively) and abstainers (0.6 ± 0.89, 0, and 0, respectively). No differences were found in MCV and GGT among groups. There were significant correlations between whole blood and dried blood spot PEth levels and AUDIT scores (Spearman's r = 0.745 and 0.738, P < 0.0001, respectively), and whole blood and dried blood spot PEth levels were significantly correlated (0.899, P < 0.0001). CONCLUSIONS: PEth levels measured in whole blood and dried blood spots were significantly greater in binge drinkers compared to abstainers and moderate drinkers, and these levels were positively correlated with AUDIT scores.

Antiangiogenic actions of vascular endothelial growth factor-A165b, an inhibitory isoform of vascular endothelial growth factor-A, in human obesity.

BACKGROUND: Experimental studies suggest that visceral adiposity and adipose tissue dysfunction play a central role in obesity-related cardiometabolic complications. Impaired angiogenesis in fat has been implicated in the development of adipose tissue hypoxia, capillary rarefaction, inflammation, and metabolic dysregulation, but pathophysiological mechanisms remain unknown. In this study, we examined the role of a novel antiangiogenic isoform of vascular endothelial growth factor-A (VEGF-A), VEGF-A165b, in human obesity. METHODS AND RESULTS: We biopsied paired subcutaneous and visceral adipose tissue in 40 obese subjects (body mass index, 45±8 kg/m(2); age, 45±11 years) during bariatric surgery and characterized depot-specific adipose tissue angiogenic capacity using an established ex vivo assay. Visceral adipose tissue exhibited significantly blunted angiogenic growth compared with subcutaneous fat (P<0.001) that was associated with marked tissue upregulation of VEGF-A165b (P=0.004). The extent of VEGF-A165b expression correlated negatively with angiogenic growth (r=-0.6, P=0.006). Although recombinant VEGF-A165b significantly impaired angiogenesis, targeted inhibition of VEGF-A165b with neutralizing antibody stimulated fat pad neovascularization and restored VEGF receptor activation. Blood levels of VEGF-A165b were significantly higher in obese subjects compared with lean control subjects (P=0.02), and surgical weight loss induced a marked decline in serumVEGF-A165b (P=0.003). CONCLUSIONS: We demonstrate that impaired adipose tissue angiogenesis is associated with overexpression of a novel antiangiogenic factor, VEGF-A165b, that may play a pathogenic role in human adiposopathy. Moreover, systemic upregulation of VEGF-A165b in circulating blood may have wider-ranging implications beyond the adipose milieu. VEGF-A165b may represent a novel area of investigation to gain further understanding of mechanisms that modulate the cardiometabolic consequences of obesity.

Cyclooxygenase inhibition improves endothelial vasomotor dysfunction of visceral adipose arterioles in human obesity.

OBJECTIVE: The purpose of this study was to determine whether cyclooxygenase inhibition improves vascular dysfunction of adipose microvessels from obese humans. DESIGN AND METHODS: In 20 obese subjects (age 37 ± 12 years, BMI 47 ± 8 kg/m²), subcutaneous and visceral fat were collected during bariatric surgery and characterized for adipose depot-specific gene expression, endothelial cell phenotype, and microvascular function. Vasomotor function was assessed in response to endothelium-dependent agonists using videomicroscopy of small arterioles from fat. RESULTS: Arterioles from visceral fat exhibited impaired endothelium-dependent, acetylcholine-mediated vasodilation, compared to the subcutaneous depot (P < 0.001). Expression of mRNA transcripts relevant to the cyclooxygenase pathway was upregulated in visceral compared to subcutaneous fat. Pharmacological inhibition of cyclooxygenase with indomethacin improved endothelium-dependent vasodilator function of arterioles from visceral fat by twofold (P = 0.01), whereas indomethacin had no effect in the subcutaneous depot. Indomethacin increased activation via serine-1177 phosphorylation of endothelial nitric oxide synthase in response to acetylcholine in endothelial cells from visceral fat. Inhibition of endothelial nitric oxide synthase with N(ω)-nitro-L-arginine methyl ester abrogated the effects of cyclooxygenase-inhibition suggesting that vascular actions of indomethacin were related to increased nitric oxide bioavailability. CONCLUSIONS: Our findings suggest that cyclooxygenase-mediated vasoconstrictor prostanoids partly contribute to endothelial dysfunction of visceral adipose arterioles in human obesity.

Insulin status and vascular responses to weight loss in obesity.

OBJECTIVES: The aim of this study was to determine whether the effects of weight loss on arterial function are differentially modified by insulin status. BACKGROUND: Clinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are currently unknown. METHODS: We prospectively followed 208 overweight or obese patients (body mass index [BMI] ≥25 kg/m(2)) receiving medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight-loss intervention and stratified analyses by median plasma insulin levels. RESULTS: Patients age 45 ± 1 years, with BMI 45 ± 9 kg/m(2), experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 µIU/ml; n = 99), ≥10% weight loss (compared with <10%) significantly improved brachial artery macrovascular flow-mediated vasodilation and microvascular reactive hyperemia (p < 0.05 for all). By contrast, vascular function did not change significantly in the lower insulin group (≤12 µIU/ml; n = 109) despite a similar degree of weight loss. In analyses using a 5% weight loss cut point, only microvascular responses improved in the higher insulin group (p = 0.02). CONCLUSIONS: Insulin status is an important determinant of the positive effect of weight reduction on vascular function with hyperinsulinemic patients deriving the greatest benefit. Integrated improvement in both microvascular and macrovascular function was associated with ≥10% weight loss. Reversal of insulin resistance and endothelial dysfunction may represent key therapeutic targets for cardiovascular risk reduction in obesity.