Assessment of Hypertension Complications and Health Service Use 5 Years After Implementation of a Multicomponent Intervention.

Importance: There is a lack of information regarding the impact of implementing a protocol-driven, team-based, multicomponent intervention in public primary care settings on hypertension-related complications and health care burden over the long term. Objective: To compare hypertension-related complications and health service use at 5 years among patients managed with Risk Assessment and Management Program for Hypertension (RAMP-HT) vs usual care. Design, Setting, and Participants: In this population-based prospective matched cohort study, patients were followed up until the date of all-cause mortality, an outcome event, or last follow-up appointment before October 2017, whichever occurred first. Participants included 212 707 adults with uncomplicated hypertension managed at 73 public general outpatient clinics in Hong Kong between 2011 and 2013. RAMP-HT participants were matched to patients receiving usual care using propensity score fine stratification weightings. Statistical analysis was conducted from January 2019 to March 2023. Interventions: Nurse-led risk assessment linked to electronic action reminder system, nurse intervention, and specialist consultation (as necessary), in addition to usual care. Main Outcomes and Measures: Hypertension-related complications (cardiovascular diseases, end-stage kidney disease), all-cause mortality, public health service use (overnight hospitalization, attendances at accident and emergency department, specialist outpatient clinic, and general outpatient clinic). Results: A total of 108 045 RAMP-HT participants (mean [SD] age: 66.3 [12.3] years; 62 277 [57.6%] female) and 104 662 patients receiving usual care (mean [SD] age 66.3 [13.5] years; 60 497 [57.8%] female) were included. After a median (IQR) follow-up of 5.4 (4.5-5.8) years, RAMP-HT participants had 8.0% absolute risk reduction in cardiovascular diseases, 1.6% absolute risk reduction in end-stage kidney disease, and 10.0% absolute risk reduction in all-cause mortality. After adjusting for baseline covariates, the RAMP-HT group was associated with lower risk of cardiovascular diseases (hazard ratio [HR], 0.62; 95% CI, 0.61-0.64), end-stage kidney disease (HR, 0.54; 95% CI, 0.50-0.59), and all-cause mortality (HR, 0.52; 95% CI, 0.50-0.54) compared with the usual care group. The number needed to treat to prevent 1 cardiovascular disease event, end-stage kidney disease, and all-cause mortality was 16, 106, and 17, respectively. RAMP-HT participants had lower hospital-based health service use (incidence rate ratios ranging from 0.60 to 0.87) but more general outpatient clinic attendances (IRR, 1.06; 95% CI, 1.06-1.06) compared with usual care patients. Conclusions and Relevance: In this prospective matched cohort study involving 212 707 primary care patients with hypertension, participation in RAMP-HT was associated with statistically significant reductions in all-cause mortality, hypertension-related complications, and hospital-based health service use after 5 years.

Changes in Adiposity without Impacting Bone Health in Nine- to Twelve-Year-Old Children with Overweight and Obesity after a One-Year Family-Centered Lifestyle Behavior Intervention.

Background: Few family-centered lifestyle interventions (FCLIs) for children with overweight or obesity (OW/OB) have assessed regional adiposity and bone health. This study assessed changes in adiposity in 9- to 12-year olds with OW/OB in a 1-year FCLI. Methods: Children were randomized to FCLI (six registered dietitian-led sessions) or no intervention (Control, CTRL). The FCLI focused on physical activity, nutrition education, and behavioral counseling children with families present. Assessments occurred at baseline and every 3 months for 1 year to assess changes in waist circumference (WC), body mass index for age-and-sex Z-scores (BAZ), body composition (dual-energy x-ray absorptiometry), and cardiometabolic biomarkers. Mixed models were used to determine the effects of group and time or group-by-time interactions for all outcomes. Results: Sixty children (age: 11.1 ± 1.1 years, BAZ: 2.7 ± 0.6) were enrolled; 55 participants (n = 28 CTRL, n = 27 FCLI) completed the study. There were no between group differences from baseline to follow-up for any measure. The FCLI group had significant decreases in BAZ over 12 months (-0.18 ± 0.27, p = 0.03) but not CTRL (-0.05 ± 0.32, p = 0.92). WC and android fat mass did not change in FCLI (p > 0.20) but increased in CTRL (p < 0.02). Whole body bone area, content, and areal bone mineral density (aBMD) increased in both groups (p < 0.010); whole body aBMD Z-score decreased by 5.8% and 1.6% in CTRL and FCLI, respectively (p < 0.001). There were no significant within group changes in biomarkers. Conclusion: The FCLI resulted in small reductions in BAZ and a plateau in android fat mass, which suggest that FCLIs are suitable as an intervention for 9- to 12-year-old children with OW/OB. Clinical Trial Registration number: NCT01290016.

Increased adiposity in children with obesity is associated with low red blood cell omega-3 fatty acid status and inadequate polyunsaturated fatty acid dietary intake.

The association between total dietary fat intake and measures of body fatness in children with obesity remains inconsistent. This study aimed to determine whether dietary long-chain polyunsaturated fatty acids (LCPUFA) and LCPUFA status relate to body composition in children with obesity. Children (n = 63, 9.0 ± 0.2 year, BMI Z-score 3.1 ± 0.2) were divided into tertiles of percentage body fat assessed by dual-energy X-ray absorptiometry. Diet was assessed 3-days food diaries. Fatty acid proportions in red blood cells (RBC) were measured by gas chromatography. Data stratified by sex and Tanner stages were compared with a MIXED model ANOVA. Associations between RBC fatty acid status and dietary intakes were examined with Spearman correlation. Moderate correlations were observed between RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) proportions, dietary EPA and DHA (r = 0.39, P < .05) as well as fish servings (r = 0.33, P < .05). Dietary LCPUFA did not differ among tertiles. Children in tertile 3 had lower RBC α-linolenic acid (-40%) and EPA + DHA (-15%) proportions adjusted for age, Tanner stages and race compared with tertile 1. The lower omega-3 LCPUFA status in children with greater adiposity is consistent with suboptimal intakes of omega-3 LCPUFA and fish in the diet.

Arachidonic acid status negatively associates with forearm bone outcomes and glucose homeostasis in children with an overweight condition or obesity.

Long-chain polyunsaturated fatty acids are implicated in musculoskeletal health in adults. This study examined whether fatty acid status relates to bone health outcomes in children with overweight condition or obesity (body mass index z score, 3.1 ± 0.1; age, 9.0 ± 0.2 years; n = 108). Nondominant forearm bone density (distal one-third), geometry (4% site), and soft tissue composition (66%) were assessed using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Red blood cell (RBC) fatty acid profile and indices of glucose homeostasis were measured. Differences in outcomes among RBC arachidonic acid (AA, C20:4n-6) tertiles were tested using mixed-model ANOVA. Ultra-, mid-, and total-distal forearm bone mineral content, adjusted for sex, age, percentage body fat, race, and forearm length, were 10% to 13% greater in children in the first AA tertile relative to the third. Children in the second tertile had the highest bone cross-sectional area and estimated strength at the 66% radius. Muscle cross-sectional area was 15% lower in the third tertile compared with the first, along with higher fasting insulin concentrations (27%) and homeostasis model of assessment estimate of insulin resistance (31%). Higher RBC AA status aligns with deficits in forearm bone mass, geometry, and muscle mass in children with excess adiposity and early signs of insulin resistance. Novelty Higher arachidonic acid status is associated with lower forearm bone mass in children with overweight condition or obesity. Children with higher arachidonic acid status had increased fasting insulin concentrations and indices of insulin resistance.

Arachidonic acid exacerbates diet-induced obesity and reduces bone mineral content without impacting bone strength in growing male rats.

Long-chain polyunsaturated fatty acids modulate bone mass and adipocyte metabolism. Arachidonic acid (AA, C20:4 n-6) is elevated in obesity and postulated to stimulate bone resorption. This study aimed to determine the effect of AA on bone mass, quality, and adiposity in diet-induced obesity during growth. Male Sprague-Dawley rats (n=42, 4-week) were randomized into groups fed a control diet (CTRL, AIN-93G), high-fat diet (HFD, 35% kcal fat) or HFD + AA (1% w/w diet) for 6 weeks. Body composition, bone mineral density and microarchitecture were measured using dual-energy X-ray absorptiometry and micro-computed tomography. Red blood cell fatty acid profile was measured with gas chromatography. Group differences were evaluated using repeated measures two-way analysis of variance with Tukey-Kramer post hoc testing. Total energy intake did not differ among diet groups. At week 6, HFD + AA had significantly greater body fat % (12%), body weight (6%) and serum leptin concentrations (125%) than CTRL, whereas visceral fat (mass and %, assessed with micro-computed tomography) was increased in both HFD and HFD + AA groups. HFD + AA showed reduced whole body bone mineral content and femur mid-diaphyseal cortical bone cross-sectional area than HFD and CTRL, without impairment in bone strength. Contrarily, HFD + AA had greater femur metaphyseal trabecular vBMD (35%) and bone volume fraction (5%) compared to controls. Inclusion of AA elevated leptin concentrations in male rats. The early manifestations of diet-induced obesity on bone mass were accelerated with AA. Studies of longer duration are needed to clarify the effect of AA on peak bone mass following growth cessation.

Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs.

Dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, and micro-computed tomography techniques are discordant for bone density and geometry measurements in the guinea pig.

This study aims to examine agreement among bone mineral content (BMC) and density (BMD) estimates obtained using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), and micro-computed tomography (µCT) against high-resolution µCT and bone ash of the guinea pig femur. Middle-aged (n = 40, 86 weeks) male guinea pigs underwent in vivo followed by ex vivo DXA (Hologic QDR 4500A) scanning for intact and excised femur BMC and areal density. To assess bone architecture and strength, excised femurs were scanned on pQCT (Stratec XCT 2000L) as well as on two µCT scanners (LaTheta LCT-200; Skyscan 1174), followed by three-point bending test. Reproducibility was determined using triplicate scans; and agreement assessed using Bland-Altman plots with reference methods being high-resolution µCT (Skyscan) for BMD and bone ashing for BMC. All techniques showed satisfactory ex vivo precision (CV 0.05-4.3 %). However, bias compared to the reference method was highest (207.5 %) in trabecular bone volume fraction (BV/TV) measured by LaTheta, and unacceptable in most total femur and cortical bone measurements. Volumetric BMD (vBMD) and BV/TV derived by LaTheta and pQCT at the distal metaphysis were biased from the Skyscan by an average of 49.3 and 207.5 %, respectively. Variability of vBMD, BV/TV and cross-sectional area at the diaphysis ranged from -5.5 to 30.8 %. LaTheta best quantified total femur BMC with an upper bias of 3.3 %. The observed differences among imaging techniques can be attributable to inherent dissimilarity in construction design, calibration, segmentation and scanning resolution used. These bone imaging tools are precise but are not comparable, at least when assessing guinea pig bones.

Orchidectomy-induced alterations in volumetric bone density, cortical porosity and strength of femur are attenuated by dietary conjugated linoleic acid in aged guinea pigs.

Age-related osteoporosis and sarcopenia are ascribed in part to reductions in anabolic hormones. Dietary conjugated linoleic acid (CLA) improves lean and bone mass, but its impact during androgen deficiency is not known. This study tested if CLA would attenuate the effects of orchidectomy (ORX)-induced losses of bone and lean tissue. Male guinea pigs (n=40; 70-72 weeks), were randomized into four groups: (1) SHAM+Control diet, (2) SHAM+CLA diet, (3) ORX+Control diet, (4) ORX+CLA diet. Baseline blood sampling and dual-energy X-ray absorptiometry (DXA) scans were conducted, followed by surgery 4 days later with the test diets started 7 days after baseline sampling. Serial blood sampling and DXA scans were repeated 2, 4, 8 and 16 weeks on the test diets. Body composition and areal BMD (aBMD) of whole body, lumbar spine, femur and tibia were measured using DXA. At week 16, muscle protein fractional synthesis rate (FSR), volumetric BMD (vBMD), microarchitecture and bone strength were assessed. Body weight declined after SHAM and ORX surgery, with slower recovery in the ORX group. Dietary CLA did not affect weight or lean mass, but attenuated gains in fat mass. Lean mass was stable in SHAM and reduced in ORX by 2 weeks with whole body and femur bone mineral content (BMC) reduced by 4 weeks; CLA did not alter BMC. By week 16 ORX groups had lower free testosterone and myofibrillar FSR, yet higher cortisol, osteocalcin and ionized calcium with no alterations due to CLA. ORX+Control had higher prostaglandin E2 (PGE2) and total alkaline phosphatase compared to SHAM+Control whereas ORX+CLA were not different from SHAM groups. Femur metaphyseal vBMD was reduced in ORX+CTRL with the reduction attenuated by CLA. Femur cortical thickness (Ct.Th.) and biomechanical strength were reduced and cortical porosity (Ct.Po.) elevated by ORX and attenuated by CLA. This androgen deficient model with a sarcopenic-osteoporotic phenotype similar to aging men responded to dietary CLA with significant benefits to femur density and strength.