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BACKGROUND Drug concentration in blood or urine is an acknowledged method to detect nonadherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension (HT). METHODS Patients were ≥18 years on stable treatment with at least 2 antihypertensive agents. We planned to randomize 80 nonadherent patients with a systolic daytime ambulatory BP ≥135 mm Hg to TDM intervention or not. The control group and the study personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on the disease process and the importance of BP treatment were given to both groups. RESULTS From 2017 to 2022, we randomized 46 diagnosed nonadherent from a total of 606 patients with uncontrolled HT. The TDM group had a 6.7 (±14.5) mm Hg reduction from 147.9 (±10.3) to 141.1 (±14.1) mm Hg, and the control group experienced a 7.3 (±13.2) mm Hg reduction from 147.1 (±9.2) to 139.1 (±17.4) mm Hg, P  = 0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at 3 months, P  = 0.51. CONCLUSIONS In our prospective multicenter clinical trial of uncontrolled and nonadherent hypertensive patients, we found no additional effect of TDM on BP and drug adherence compared with standard care. CLINICAL TRIALS REGISTRATION Trial Number NCT03209154 , www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Available data of event-based clinical outcomes trials show that little evidence supports the guidelines recommendations to lower blood pressure (BP) to <130/80 mmHg in middle-aged and elderly people with type 2 diabetes mellitus and hypertension. We addressed this issue by post-hoc analysing the risk of cardiovascular (CV) events in mostly elderly high-risk hypertensive patients with type 2 diabetes mellitus participating in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial. Patients (n = 5250) were divided into 4 groups according to the proportion of on-treatment visits before the occurrence of an event (<25% to ≥ 75%) in which BP was reduced to <140/90 or <130/80 mmHg. After adjustment for baseline demographic differences between groups, a reduction in the proportion of visits in which BP achieved <140/90 mmHg accompanied a progressive increase in the risk of CV mortality and morbidity as well as of cause-specific events such as stroke, myocardial infarction and heart failure. A progressive reduction in the proportion of visits in which BP was reduced <130/80 mmHg did not have any effect on CV risks. In mostly elderly high-risk hypertensive patients with type 2 diabetes mellitus participating in the VALUE trial, achieving more frequently BP <140/90 mmHg showed a marked protective effect on overall and all cause-specific cardiovascular outcomes. This was not the case for a more frequent achievement of the more intensive BP target, i.e. <130/80 mmHg. [ABSTRACT FROM AUTHOR]

Abstract Background To study mortality rate and causes of death among all hospitalized opioid addicts treated for self-poisoning or admitted for voluntary detoxification in Oslo between 1980 and 1981, and to compare their mortality to that of the general population. Methods A prospective cohort study was conducted on 185 opioid addicts from all medical departments in Oslo who were treated for either self-poisoning (n = 93, 1980), voluntary detoxification (n = 75, 1980/1981) or both (n = 17). Their median age was 24 years; with a range from 16 to 41, and 53% were males. All deaths that had occurred by the end of 2000 were identified from the Central Population Register. Causes of death were obtained from Statistics Norway. Standardized mortality ratios (SMRs) were computed for mortality, in general, and in particular, for different causes of death. Results During a period of 20 years, 70 opioid addicts died (37.8%), with a standardized mortality ratio (SMR) equal to 23.6 (95% CI, 18.7–29.9). The SMR remained high during the whole period, ranging from 32.4 in the first five-year period, to 13.4 in the last five-year period. There were no significant differences in SMR between self-poisonings and those admitted for voluntarily detoxification. The registered causes of death were accidents (11.4%), suicide (7.1%), cancer (4.3%), cardiovascular disease (2.9%), other violent deaths (2.9%), other diseases (71.4%). Among the 50 deaths classified as other diseases, the category "drug dependence" was listed in the vast majority of cases (37 deaths, 52.9% of the total). SMRs increased significantly for all causes of death, with the other diseases group having the highest SMR; 65.8 (95% CI, 49.9–86.9). The SMR was 5.4 (95% CI, 1.3–21.5) for cardiovascular diseases, and 4.3 (95% CI, 1.4–13.5) for cancer. The SMR was 13.2 (95% CI, 6.6–26.4) for accidents, 10.7 (95% CI, 4.5–25.8) for suicides, and 28.6 (95% CI, 7.1–114.4) for other violent deaths. Conclusion The risk of death among opioid addicts was significantly higher for all causes of death compared with the general population, implying a poor prognosis over a 20-year period for this young patient group.

Abstract Background Possible mechanisms behind psychophysiological hyperreactivity may be located at a cognitive-emotional level. Several personality traits have been associated with increased cardiovascular reactivity. Subjects with white coat hypertension, which may constitute a kind of hyperreactivity, are found to suppress their emotions and adapt to the surroundings to a larger extent than controls. We hypothesized in this study that a) stress reactivity is related to personality, and that b) responses to cold pressor test (CPT) and mental stress test (MST) are associated with different personality traits. Methods 87 men were selected from the 1st, 50th and 99th percentile of a blood pressure screening. Cardiovascular and catecholamine responses to MST and CPT were recorded. Fifteen personality traits were assessed using the Karolinska Scale of Personality. Possible independent explanatory predictors for cardiovascular and catecholamine variables at baseline and during stress were analyzed in multiple linear regression analyses using a stepwise forward procedure. Results Multiple regression analyses showed that muscular tension (β = 0.298, p = 0.004), irritability (β = 0.282, p = 0.016), detachment (β = 0.272, p = 0.017), psychasthenia (β = 0.234, p = 0.031) and somatic anxiety (β = 0.225, p = 0.046) were significant explanatory variables of reactivity to CPT. During MST, verbal aggression (β = -0.252, 0.031) and detachment (β = 0.253, p = 0.044) were significant predictors of norepinephrine and diastolic blood pressure response, respectively. Based on KSP-trait quartiles, delta (Δ) systolic (p = 0.025) and Δ diastolic blood pressure (p = 0.003) during MST were related to detachment score, with the highest reactivity in the 4th quartile, while Δ norepinephrine was significantly related to muscular tension (p = 0.033). Δ systolic and Δ diastolic blood pressure responses to CPT were dependent on detachment (p = 0.049 and p = 0.011, respectively) and psychasthenia (p = 0.020 and p = 0.015), while high verbal aggression was associated with lower reactivity measured by Δ norepinephrine (p = 0.037). Conclusion The present study indicates that stress reactivity is clearly related to different personality traits, without any single trait being dominant over others. Furthermore, personality seems to have as much, or even more, importance of predicting responses to CPT than responses to MST.

Renal sympathetic denervation (RDN) is again gaining interest as recent well-designed trials have demonstrated reduced ambulatory blood pressure (BP) after RDN. However, the hemodynamic mechanisms have not been elucidated. We aimed for the first time to investigate the effect of RDN on the "Hallmark of Hypertension" namely increased systemic vascular resistance index (SVRI). We investigated SVRI change in patients with true treatment-resistant hypertension randomised to RDN (n = 9) or drug adjusted control (n = 9). Treatment-resistant hypertension was defined as office systolic BP ≥ 140 mmHg despite ≥ 3 antihypertensive drugs including a diuretic. True treatment-resistant hypertension was confirmed prior to inclusion with ambulatory daytime systolic BP ≥ 135 mmHg immediately after witnessed intake of antihypertensive drugs. Hemodynamic variables were recorded with thoracic impedance cardiography at baseline and at three and six months follow-up after RDN. This non-invasive method also guided further tailoring of drug treatment in the control group aiming to normalise hemodynamic variables and BP. From three to six months follow-up after RDN, SVRI decreased with a median of −611 dyn*s*m2/cm5 [IQR −949 to −267] (p < 0.01), while supine mean BP decreased with a median of −11 mmHg [IQR −21 to −3] (p = 0.02). In the same period, SVRI in the control group was reduced with −674 dyn*s*m2/cm5 [IQR −1,309 to −340] (p < 0.01), while supine mean BP decreased with −15 mmHg [IQR −29 to −6] (p = 0.01). Thus, hemodynamic variables and BP in the two groups normalised in parallel. Our data suggest that in patients with true treatment-resistant hypertension, renal sympathetic denervation lowers BP by reducing systemic vascular resistance of similar size as in the control group with careful individual selection of antihypertensive drugs and dose titration. [ABSTRACT FROM AUTHOR]