We tested the hypothesis that genetic variation in the beta-2 adrenoceptor gene is associated with a genetic predisposition to hypertension. Offspring of two hypertensive parents were compared with offspring of two normotensive parents. The subjects were participants of the Bergen Blood Pressure Study, where couples were recruited in 1963 to 1964 and re-examined in 1990. We studied offspring of those couples in which both partners were either hypertensive or normotensive in both examinations. Twenty-three hypertensive and 22 normotensive families met the inclusion criteria. DNA samples from the first born of hypertensive family-history offspring and normotensive family-history offspring were analyzed. We used multiplex sequencing and specifically examined the promoter and the N-terminal portion of the beta-2 adrenoceptor gene. We found four genetic variants: at position -47, a C-->T substitution in the 5' leader cistron causing an Arg-->Cys exchange, at -20, a T-->C substitution, at +46 an A-->G substitution leading to an Arg16-->Gly exchange, and at +79, a C-->G substitution leading to a Gln27-->Glu exchange. The frequency of the Arg16 allele was significantly higher in the hypertensive family-history offspring compared to normotensive family-history offspring (58% vs. 28% P < 0.011). We constructed haplotypes for the four intragenic variants and found significant linkage dysequilibrium. In particular, the 5' leader cistron mutant with the wild type alleles at the other loci was significantly more frequent in offspring of hypertensive parents, compared to offspring of normotensive parents. We also performed a relative risk analysis comparing the Gly/Gly, Arg/Gly, and Arg/Arg alleles, which implicated the Arg-containing allele. Finally, we analyzed the effect of genotype on blood pressure in the offspring. We found a significant step-wise effect for all four polymorphisms examined. Our data suggest that the Arg variant of the Arg-->Gly exchange is associated with parental hypertension and higher blood pressure values in this northern European population.

Background Chronic heart failure (CHF) is a prevalent disease, and CHF patients are recommended to participate in cardiac rehabilitation programs. Due to frailty and rural living, many CHF patients refuse to do so. To meet these challenges, there is need of a more convenient and efficient rehabilitation system. A home-based telerehabilitation program was designed to enable CHF patients to exercise via video-conferencing in their homes, allowing two-way communication with their therapist, and for patients to exercise together. Purpose We aimed to evaluate the feasibility of a home-based telerehabilitation exercise program designed for CHF patients. Methods 67 subjects were included in a two-arm prospective randomized controlled trial if they had stable CHF, were on optimal medical therapy, and refused to participate in standard outpatient rehabilitation. All subjects participated in a 2-day “Living with heart failure” course. The intervention group (n=30) was educated in the use of a tablet computer, a video-conferencing app, and an app with exercise videos, before they received home-based telerehabilitation exercise twice a week for 3 months. Each exercise session consisted of 20 min warm-up, followed by 4x4 min high intensity intervals with 3 min active breaks, and 15 min calm down. Outcomes, measured at baseline and 3 months, included the 6-minute walk test, the Minnesota living with heart failure Questionnaire (MLHFQ), adherence, adverse events, satisfaction, and patient reported measures of safety, technical aspects, and motivational factors. Results Mean age was 68 (65.6–71.1) years (82% male). By the 6-minute walk test, the exercise group increased their walking distance with 18 m from baseline 451 m, p=0.07. No change (+0.8 m) was seen in the control group from baseline (478 m) to 3 months, but no significant difference between groups (p=0.20). We found a significant decrease in MLHFQ score for the exercise group (baseline 42.6, change −13.8, p=0.003), and for the control group (baseline 41.2, change −12.6, p=0.002), with no difference between groups (p=0.83). ≥80% fulfilled 80% of 24 exercises. One drop-out was registered, and no adverse events were reported during exercise. In total 96% (26/27) reported that they felt safe during home-based exercise via videoconferencing and 96% (24/25) reported that the intervention gave motivation to continue exercising on their own. Some minor technical issues with the videoconference software was present in 58% (15/26). Conclusion Home-based exercise training supported by real-time supervision by telemedicine was feasible, with high adherence and high level of patients' satisfaction. Telerehabilitation increased 6-minute walking distance and quality of life in CHF patients, but the changes were not statistically significant compared to controls. Despite some technical issues with the software and equipment used, the participants reported high motivation to further exercise. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Central Norway Regional Health Authority

Aims Despite strong recommendations, outpatient cardiac rehabilitation is underused in chronic heart failure (CHF) patients. Possible barriers are frailty, accessibility, and rural living, which may be overcome by telerehabilitation. We designed a randomized, controlled trial to evaluate the feasibility of a 3‐month real‐time, home‐based telerehabilitation, high‐intensity exercise programme for CHF patients who are either unable or unwilling to participate in standard outpatient cardiac rehabilitation and to explore outcomes of self‐efficacy and physical fitness at 3 months post‐intervention. Methods and results CHF patients with reduced (≤40%), mildly reduced (41–49%), or preserved ejection fraction (≥50%) (n = 61) were randomized 1:1 to telerehabilitation or control in a prospective controlled trial. The telerehabilitation group (n = 31) received real‐time, home‐based, high‐intensity exercise for 3 months. Inclusion criteria were (i) ≥18 years, (ii) New York Heart Association class II‐III, stable on optimized medical therapy for >4 weeks, and (iii) N‐terminal pro‐brain natriuretic peptide >300 ng/L. All participants participated in a 2‐day ‘Living with heart failure’ course. No other intervention beyond standard care was provided for controls. Outcome measures were adherence, adverse events, self‐reported outcome measures, the general perceived self‐efficacy scale, peak oxygen uptake (VO2peak) and a 6‐min walk test (6MWT). The mean age was 67.6 (11.3) years, and 18% were women. Most of the telerehabilitation group (80%) was adherent or partly adherent. No adverse events were reported during supervised exercise. Ninety‐six per cent (26/27) reported that they felt safe during real‐time, home‐based telerehabilitation, high‐intensity exercise, and 96% (24/25) reported that, after the home‐based supervised telerehabilitation, they were motivated to participate in further exercise training. More than half the population (15/26) reported minor technical issues with the videoconferencing software. 6MWT distance increased significantly in the telerehabilitation group (19 m, P = 0.02), whereas a significant decrease in VO2peak (−0.72 mL/kg/min, P = 0.03) was observed in the control group. There were no significant differences between the groups in general perceived self‐efficacy scale, VO2peak, and 6MWT distance after intervention or at 3 months post‐intervention. Conclusions Home‐based telerehabilitation was feasible in chronic heart failure patients inaccessible for outpatient cardiac rehabilitation. Most participants were adherent when given more time and felt safe exercising at home under supervision, and no adverse events occurred. The trial suggests that telerehabilitation can increase the use of cardiac rehabilitation, but the clinical benefit of telerehabilitation must be evaluated in larger trials.

Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P <0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P <0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P <0.01) and total daily pills (5.5 versus 4.4 pills, P =0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P <0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03209154.

Plasma atrial natriuretic peptide (ANP), plasma and 24-h urine catecholamines, plasma renin activity (PRA), and serum aldosterone were studied in offspring of hypertensive and normotensive families [n = 82; age 37 +/- 7 years (mean +/- SD)]. Despite higher age, higher blood pressure, and higher urine excretion of catecholamines--all of which are factors associated with increased ANP levels--the mean basal plasma ANP concentration tended to be lower in offspring of hypertensive than normotensive families. The same pattern was found in all age-tertiles, and the between-group difference was statistically significant in subjects aged 34-39 years (p < 0.01). Also, the family history of hypertension was associated with low ANP levels after covariate adjustment (p < 0.05). The 24-h urine excretion of epinephrine and norepinephrine tended to be higher in offspring of hypertensive than normotensive families while the morning venous plasma levels were similar. The ratio between venous plasma ANP and norepinephrine was lower in offspring of hypertensive than normotensive families (p < 0.05). PRA, serum aldosterone level, and 24-h urine excretion of dopamine did not differ significantly between groups. Inappropriately low basal plasma ANP concentrations and low plasma ANP/norepinephrine ratios may be related to the development of essential hypertension in offspring of hypertensive families.

Cardiac morphology and function were determined by echocardiography in normotensive offspring of 23 hypertensive and 22 normotensive families. The family histories of hypertension or normotension were based on 27 years' observation of parental blood pressure. Pulsed Doppler and M-mode echocardiography were performed in standard views. Out of the total 109 offspring, 94 participated in the present study (age (mean +/- SD) 36 +/- 7 years). Left ventricular posterior wall thickness was higher in offspring of hypertensive than normotensive families (10.1 +/- 1.7 vs. 9.3 +/- 1.5 mm; p < 0.05). Offspring of hypertensive families had lower transmitral early/late peak flow velocities (p < 0.001) and higher transmitral late peak flow velocities (p < 0.001) than offspring of normotensive families, but the differences between groups became inconsistent after adjustment for confounding variables (including left ventricular structural parameters). On the other hand, the family history of hypertension was consistently associated with increased transmitral early peak flow velocity and increased transmitral acceleration and deceleration slopes p < 0.05), a pattern suggesting increased left ventricular stiffness. Increased posterior wall thickness and diastolic functional changes may indicate cardiac hypertrophy and decreased left ventricular compliance and precede the development of hypertension in offspring of hypertensive families.

AimsTo investigate the associations of cardiorespiratory fitness with cardiac, vascular, renal and cardiorenal characteristics in chronic heart failure in a telerehabilitation randomized clinical trial. Secondly, to evaluate the associations of cardiorenal syndrome with the effects of exercise. Methods and resultsSixty-nine heart failure patients attended baseline examination, and 61 patients were randomly assigned 1:1 to 3-month telerehabilitation or control. Data were collected at baseline and 3-month post-intervention, including echocardiography and vascular ultrasound, laboratory tests, exercise test with peak oxygen consumption (VO 2peak ) measurement and 6-min walk test (6MWT). Baseline VO 2peak and 6MWT distance was 0.85 mL*min À1 *kg À1 lower and 20 m shorter per 10 mL/min/1.73m 2 lower estimated glomerular filtration rate (both P < 0.001). Heart failure patients with cardiorenal syndrome had 3.5 (1.1) mL*min À1 *kg À1 lower VO 2peak and diastolic dysfunction grade 2-3, and elevated filling pressure was >50% more common compared with those without (all P < 0.05). At the 3-month post-intervention follow-up, only the non-CRS patients in the intervention group increased VO 2peak (0.73 (0.51) mL*min À1 *kg À1 ), whereas VO 2peak in the CRS subpopulation of controls decreased (À1.34 (0.43) mL*min À1 *kg À1 ). Cardiorenal syndrome was associated with a decrease in VO 2peak in CRS patients compared with non-CRS patients, À0.91 (0.31) vs. 0.39 (0.35) mL*min À1 *kg À1 respectively, P = 0.013. Conclusions Cardiorenal syndrome was negatively associated with VO 2peak and 6MWT distance in chronic HF, and the associations were stronger than for heart failure phenotypes and other characteristics. The effect of exercise was negatively associated with cardiorenal syndrome. Exercise seems to be as important in heart failure patients with cardiorenal syndrome, and future studies should include CRS patients to reveal the most beneficial type of exercise.

2021) Cardiovascular outcomes at recommended blood pressure targets in middle-aged and elderly patients with type 2 diabetes mellitus compared to all middleaged and elderly hypertensive study patients with high cardiovascular risk, Blood Pressure, 30:2, 90-97,