Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

<div><p></p><p>Experimental studies suggested that statins attenuate vascular AT₁ receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; P<0.05) compared to 65%±11% before and 73%±11% after 30 days of atorvastatin treatment. Plasma angiotensin levels increased significantly after irbesartan treatment (Ang II: 17±22 before vs 52±40 pg/mL after [p = 0.048]; Ang-(1–7): 18±10 before vs 37±14 pg/mL after [p = 0.002]) compared to atorvastatin treatment (Ang II: 9±4 vs 11±10 pg/mL [p = 0.40]; Ang-(1–7): 24±9 vs 32±8 pg/mL [p = 0.023]). Our study suggests that statin treatment does not elicit major changes in angiotensin II-mediated venoconstriction or in circulating angiotensin II levels whereas angiotensin-(1–7) levels increased modestly. The discrepancy between local vascular and systemic angiotensin II responses might suggest that statin treatment interferes with blood pressure buffering reflexes.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/show/NCT00154024" target="_blank">NCT00154024</a></p></div

Dilation of preconstricted dorsal hand veins elicited by incremental histamine infusions.

<p>Between-group differences were analyzed with a two-way ANOVA. Data are expressed as mean ± SEM.</p

Time course of dorsal hand vein constriction with constant angiotensin II infusion.

<p>Infusion rate: 50 ng/min over 24 minutes before (pre) and after (post) treatment with atorvastatin. Differences between pre- and post-treatment were analyzed with a two-way ANOVA with <i>Bonferroni's post hoc</i> tests to test for differences at single time points. Data are expressed as mean ± SEM.</p

Time course of dorsal hand vein constriction with constant angiotensin II infusion.

<p>Infusion rate: 50 ng/min over 24 minutes before (pre) and after (post) treatment with irbesartan. Differences between pre- and post-treatment were analyzed with a two-way ANOVA with <i>Bonferroni's post hoc</i> tests to test for differences at single time points. Data are expressed as mean ± SEM.</p

Atorvastatin and irbesartan influences on plasma concentrations of angiotensin II.

<p>Within-group differences were analyzed with <i>Students</i> paired t-test and between-group differences with a two-way ANOVA. Data are expressed as individual values and as mean ± SEM.</p

Exercise capacity (A: VO2_max; B: 6MWT) and pulmonary capacity (C: FEV₁; D: FVC_ex) in relation to the norm values.

Exercise capacity (A: VO2max; B: 6MWT) and pulmonary capacity (C: FEV1; D: FVCex) in relation to the norm values.</p

Subject characteristics at baseline.

PurposePost-Covid-19 syndrome is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The most common symptoms include reduced exercise tolerance and capacity, fatigue, neurocognitive problems, muscle pain and dyspnea. The aim of our work was to investigate exercise capacity and markers of subjective wellbeing and their independent relation to post-COVID-19 syndrome.Patients and methodsWe examined a total of 69 patients with post-COVID-19 syndrome (23 male/46 female; age 46±12 years; BMI 28.9±6.6 kg/m2) with fatigue and a score ≥22 in the Fatigue Assessment Scale (FAS). We assessed exercise capacity on a cycle ergometer, a 6-minute walk test, the extent of fatigue (FAS), markers of health-related quality of life (SF-36 questionnaire) and mental health (HADS).ResultsOn average the Fatigue Assessment Scale was 35.0±7.4 points. Compared with normative values the VO2max/kg was reduced by 8.6±5.8 ml/min/kg (27.7%), the 6MWT by 71±96 m (11.9%), the health-related quality of life physical component score by 15.0±9.0 points (29.9%) and the mental component score by 10.6±12.8 points (20.6%). Subdivided into mild fatigue (FAS score 22–34) and severe fatigue (FAS score ≥35), patients with severe fatigue showed a significant reduction of the 6-minute walk test by 64±165 m (pConclusionPatients with post-COVID-19 syndrome show reduced maximal and submaximal physical performance as well as limitations in quality of life, particularly pronounced in the physical components. These results are essentially influenced by the severity of fatigue and implicating the need for targeted treatments.</div

Exercise capacity (A: VO2_max; B: 6MWT) and HrQoL (C: Physical component score; D: Mental component score) divided into mild and severe fatigue based on FAS score.

The framed p-values are given for differences between mild and severe fatigue as analyzed by Student t test for unpaired samples. Data are mean ± SD.</p

Subscales of the HrQoL questionnaire for men and women compared to the norm values.

Subscales of the HrQoL questionnaire for men and women compared to the norm values.</p

Low-dose, non-supervised, health insurance initiated exercise for the treatment and prevention of chronic low back pain in employees. Results from a randomized controlled trial

<div><p>Objective</p><p>Back pain is a major problem requiring pragmatic interventions, low in costs for health care providers and feasible for individuals to perform. Our objective was to test the effectiveness of a low-dose 5-month exercise intervention with small personnel investment on low back strength and self-perceived pain.</p><p>Methods</p><p>Two hundred twenty-six employees (age: 42.7±10.2 years) from three mid-size companies were randomized to 5-month non-supervised training at home (3 times/week for 20 minutes) or wait-list-control. Health insurance professionals instructed the participants on trunk exercises at the start and then supervised participants once a month.</p><p>Results</p><p>Muscle strength for back extension increased after the 5-month intervention with a significant between-group difference (mean 27.4 Newton [95%CI 2.2; 60.3]) favoring the exercise group (p = 0.035). Low back pain was reduced more in subjects after exercise than control (mean difference –0.74 cm [95%CI –1.17; –0.27], p = 0.002). No between-group differences were observed for back pain related disability and work ability. After stratified analysis only subjects with preexisting chronic low back pain showed a between-group difference (exercise versus controls) after the intervention in their strength for back extension (mean 55.7 Newton [95%CI 2.8; 108.5], p = 0.039), self-perceived pain (mean –1.42 cm [95%CI –2.32; –0.51], p = 0.003) and work ability (mean 2.1 points [95%CI 0.2; 4.0], p = 0.032). Significant between-group differences were not observed in subjects without low back pain: strength for back extension (mean 23.4 Newton [95%CI –11.2; 58.1], p = 0.184), self-perceived pain (mean –0.48 cm [95%CI –0.99; 0.04], p = 0.067) and work ability (mean –0.1 points [95%CI –0.9; 0.9], p = 0.999). An interaction between low back pain subgroups and the study intervention (exercise versus control) was exclusively observed for the work ability index (p = 0.016).</p><p>Conclusion</p><p>In middle-aged employees a low-dose, non-supervised exercise program implemented over 20 weeks improved trunk muscle strength and low back pain, and in those with preexisting chronic low back pain improved work ability.</p></div