CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification.

Vascular calcification is a severe complication of cardiovascular diseases. Previous studies demonstrated that endothelial lineage cells transitioned into osteoblast-like cells and contributed to vascular calcification. Here, we found that inhibition of cyclin-dependent kinase (CDK) prevented endothelial lineage cells from transitioning to osteoblast-like cells and reduced vascular calcification. We identified a robust induction of CDK1 in endothelial cells (ECs) in calcified arteries and showed that EC-specific gene deletion of CDK1 decreased the calcification. We found that limiting CDK1 induced E-twenty-six specific sequence variant 2 (ETV2), which was responsible for blocking endothelial lineage cells from undergoing osteoblast differentiation. We also found that inhibition of CDK1 reduced vascular calcification in a diabetic mouse model. Together, the results highlight the importance of CDK1 suppression and suggest CDK1 inhibition as a potential option for treating vascular calcification.

Intrahepatic Transcriptomics Differentiate Advanced Fibrosis and Clinical Outcomes in Adults With Fontan Circulation.

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.

Two-step regulation by matrix Gla protein in brown adipose cell differentiation.

OBJECTIVE: Bone morphogenetic protein (BMP) signaling is intricately involved in adipose tissue development. BMP7 together with BMP4 have been implicated in brown adipocyte differentiation but their roles during development remains poorly specified. Matrix Gla protein (MGP) inhibits BMP4 and BMP7 and is expressed in endothelial and progenitor cells. The objective was to determine the role of MGP in brown adipose tissue (BAT) development. METHODS: The approach included global and cell-specific Mgp gene deletion in combination with RNA analysis, immunostaining, thermogenic activity, and in vitro studies. RESULTS: The results revealed that MGP directs brown adipogenesis at two essential steps. Endothelial-derived MGP limits triggering of white adipogenic differentiation in the perivascular region, whereas MGP derived from adipose cells supports the transition of CD142-expressing progenitor cells to brown adipogenic maturity. Both steps were important to optimize the thermogenic function of BAT. Furthermore, MGP derived from both sources impacted vascular growth. Reduction of MGP in either endothelial or adipose cells expanded the endothelial cell population, suggesting that MGP is a factor in overall plasticity of adipose tissue. CONCLUSION: MGP displays a dual and cell-specific function in BAT, essentially creating a "cellular shuttle" that coordinates brown adipogenic differentiation with vascular growth during development.

Long-term secondary prevention and outcome following acute coronary syndrome: real-world results from the Swedish Primary Care Cardiovascular Database.

AIMS: Most studies of treatment adherence after acute coronary syndrome (ACS) are based on prescribed drugs and lack long-term follow-up or consecutive data on risk factor control. We studied the long-term treatment adherence, risk factor control, and its association to recurrent ACS and death. METHODS AND RESULTS: We retrospectively included 3765 patients (mean age 75 years, 40% women) with incident ACS from 1 January 2006 until 31 December 2010 from the Swedish Primary Care Cardiovascular Database of Skaraborg. All patients were followed until 31 December 2014 or death. We recorded blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), recurrent ACS, and death. We used data on dispensed drugs to calculate the proportion of days covered for secondary prevention medications. Cox regressions were used to analyse the association of achieved BP and LDL-C to recurrent ACS and death. The median follow-up time was 4.8 years. The proportion of patients that reached BP of <140/90 mm Hg was 58% at Year 1 and 66% at Year 8. 65% of the patients reached LDL-C of <2.5 mmol/L at Year 1 and 56% at Year 8; however, adherence to statins varied from 43% to 60%. Only 62% of the patients had yearly measured BP, and only 28% yearly measured LDL-C. Systolic BP was not associated with a higher risk of recurrent ACS or death. Low-density lipoprotein cholesterol of 3.0 mmol/L was associated with a higher risk of recurrent ACS {hazard ratio [HR] 1.19 [95% confidence interval (CI) 1.00-1.40]} and death HR [1.26 (95% CI 1.08-1.47)] compared with an LDL-C of 1.8 mmol/L. CONCLUSION: This observational long-term real-world study demonstrates low drug adherence and potential for improvement of risk factors after ACS. Furthermore, the study confirms that uncontrolled LDL-C is associated with adverse outcome even in this older population.

In this real-world retrospective observational study, we followed 3765 elderly patients for up to 8 years after incident acute coronary syndrome.Only a low proportion of the studied population had yearly measured blood pressure and cholesterol, a low proportion had satisfied risk factor control (blood pressure and cholesterol), and adherence to secondary prevention medication was low.In this elderly population (mean age 75 years), higher levels of low-density lipoprotein cholesterol were associated with a higher risk of recurrent coronary event and death.

Aurora Kinase A Regulates Cell Transitions in Glucocorticoid-Induced Bone Loss.

Glucocorticoid-induced bone loss is a severe and toxic effect of long-term therapy with glucocorticoids, which are currently prescribed for millions of people worldwide. Previous studies have uncovered that glucocorticoids reciprocally converted osteoblast lineage cells into endothelial-like cells to cause bone loss and showed that the modulations of Foxc2 and Osterix were the causative factors that drove this harmful transition of osteoblast lineage cells. Here, we find that the inhibition of aurora kinase A halts this transition and prevents glucocorticoid-induced bone loss. We find that aurora A interacts with the glucocorticoid receptor and show that this interaction is required for glucocorticoids to modulate Foxc2 and Osterix. Together, we identify a new potential approach to counteracting unwanted transitions of osteoblast lineage cells in glucocorticoid treatment and may provide a novel strategy for ameliorating glucocorticoid-induced bone loss.

Role of Matrix Gla Protein in Transforming Growth Factor-ß Signaling and Nonalcoholic Steatohepatitis in Mice.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a complex disease involving both genetic and environmental factors in its onset and progression. We analyzed NASH phenotypes in a genetically diverse cohort of mice, the Hybrid Mouse Diversity Panel, to identify genes contributing to disease susceptibility. METHODS: A "systems genetics" approach, involving integration of genetic, transcriptomic, and phenotypic data, was used to identify candidate genes and pathways in a mouse model of NASH. The causal role of Matrix Gla Protein (MGP) was validated using heterozygous MGP knockout (Mgp+/-) mice. The mechanistic role of MGP in transforming growth factor-beta (TGF-ß) signaling was examined in the LX-2 stellate cell line by using a loss of function approach. RESULTS: Local cis-acting regulation of MGP was correlated with fibrosis, suggesting a causal role in NASH, and this was validated using loss of function experiments in 2 models of diet-induced NASH. Using single-cell RNA sequencing, Mgp was found to be primarily expressed in hepatic stellate cells and dendritic cells in mice. Knockdown of MGP expression in stellate LX-2 cells led to a blunted response to TGF-ß stimulation. This was associated with reduced regulatory SMAD phosphorylation and TGF-ß receptor ALK1 expression as well as increased expression of inhibitory SMAD6. Hepatic MGP expression was found to be significantly correlated with the severity of fibrosis in livers of patients with NASH, suggesting relevance to human disease. CONCLUSIONS: MGP regulates liver fibrosis and TGF-ß signaling in hepatic stellate cells and contributes to NASH pathogenesis.

Hypertension management in primary health care: a survey in eight regions of Sweden.

PURPOSE: To explore hypertension management in primary healthcare (PHC). DESIGN: Structured interviews of randomly selected PHC centres (PHCCs) from December 2019 to January 2021. SETTING: Seventy-six PHCCs in eight regions of Sweden. MAIN OUTCOME MEASURES: Staffing and organization of hypertension care. Methods of measuring blood pressure (BP), laboratory tests, registration of co-morbidities and lifestyle advice at diagnosis and follow-up. RESULTS: The management of hypertension varied among PHCCs. At diagnosis, most PHCCs (75%) used the sitting position at measurements, and only 13% routinely measured standing BP. One in three (33%) PHCCs never used home BP measurements and 25% only used manual measurements. The frequencies of laboratory analyses at diagnosis were similar in the PHCCs. At follow-up, fewer analyses were performed and the tests of lipids and microalbuminuria decreased from 95% to 45% (p < 0.001) and 61% to 43% (p = 0.001), respectively. Only one out of 76 PHCCs did not measure kidney function at routine follow-ups. Lifestyle, physical activity, food habits, smoking and alcohol use were assessed in ≥96% of patients at diagnosis. At follow-up, however, there were fewer assessments. Half of the PHCCs reported dedicated teams for hypertension, 82% of which were managed by nurses. There was a great inequality in the number of patients per tenured GP in the PHCCs (median 2500; range 1300-11300) patients. CONCLUSIONS: The management of hypertension varies in many respects between PHCCs in Sweden. This might lead to inequity in the care of patients with hypertension.

Hypertension is mainly handled in primary healthcare (PHC), and this study shows important dissimilarities in organization and clinical management.Several variants in techniques and measurements of blood pressure were found between PHC centres.Lifestyle, clinical and laboratory assessments decreased at follow-ups compared to at diagnosis, specifically for lipids, microalbuminuria and electrocardiograms.Nearly half of the PHC centres reported that they had dedicated hypertension teams.

GSK3ß Inhibition Ameliorates Atherosclerotic Calcification.

Endothelial-mesenchymal transition (EndMT) drives endothelium to contribute to atherosclerotic calcification. In a previous study, we showed that glycogen synthase kinase-3ß (GSK3ß) inhibition induced ß-catenin and reduced mothers against DPP homolog 1 (SMAD1) in order to redirect osteoblast-like cells towards endothelial lineage, thereby reducing vascular calcification in Matrix Gla Protein (Mgp) deficiency and diabetic Ins2Akita/wt mice. Here, we report that GSK3ß inhibition or endothelial-specific deletion of GSK3ß reduces atherosclerotic calcification. We also find that alterations in ß-catenin and SMAD1 induced by GSK3ß inhibition in the aortas of Apoe-/- mice are similar to Mgp-/- mice. Together, our results suggest that GSK3ß inhibition reduces vascular calcification in atherosclerotic lesions through a similar mechanism to that in Mgp-/- mice.

Cell Transitions Contribute to Glucocorticoid-Induced Bone Loss.

Glucocorticoid-induced bone loss is a toxic effect of long-term therapy with glucocorticoids resulting in a significant increase in the risk of fracture. Here, we find that glucocorticoids reciprocally convert osteoblast-lineage cells into endothelial-like cells. This is confirmed by lineage tracing showing the induction of endothelial markers in osteoblast-lineage cells following glucocorticoid treatment. Functional studies show that osteoblast-lineage cells isolated from glucocorticoid-treated mice lose their capacity for bone formation but simultaneously improve vascular repair. We find that the glucocorticoid receptor directly targets Foxc2 and Osterix, and the modulations of Foxc2 and Osterix drive the transition of osteoblast-lineage cells to endothelial-like cells. Together, the results suggest that glucocorticoids suppress osteogenic capacity and cause bone loss at least in part through previously unrecognized osteoblast-endothelial transitions.

COVID-19 Infection May Drive EC-like Myofibroblasts towards Myofibroblasts to Contribute to Pulmonary Fibrosis.

COVID-19 has an extensive impact on Homo sapiens globally. Patients with COVID-19 are at an increased risk of developing pulmonary fibrosis. A previous study identified that myofibroblasts could be derived from pulmonary endothelial lineage cells as an important cell source that contributes to pulmonary fibrosis. Here, we analyzed publicly available data and showed that COVID-19 infection drove endothelial lineage cells towards myofibroblasts in pulmonary fibrosis of patients with COVID-19. We also discovered a similar differentiation trajectory in mouse lungs after viral infection. The results suggest that COVID-19 infection leads to the development of pulmonary fibrosis partly through the activation of endothelial cell (EC)-like myofibroblasts.

DASH-HF Study: A Pragmatic Quality Improvement Randomized Implementation Trial for Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Heart failure is a prevailing diagnosis of hospitalization and readmission within 6 months, and nearly a quarter of these patients die within a year. Guideline-directed medication therapies reduce risk of mortality by 73% over 2 years; however, the implementation of these therapies to their target dose in clinical practice continues to be challenging. In 2020, the Veterans Affairs (VA) Health Care System developed a HF dashboard to monitor and improve outpatient HF management. The DASH-HF (Dashboard Activated Services and Telehealth for Heart Failure) study is a randomized, pragmatic clinical trial to evaluate proactive dashboard-directed telehealth clinics to improve the use and dosing of guideline-directed medication therapy for patients with heart failure with reduced ejection fraction not on optimal guideline-directed medication therapy within the VA. METHODS: Three hundred veterans with heart failure with reduced ejection fraction met inclusion criteria with an optimization potential score (OPS) of 5 or less out of 10, representing nonoptimal guideline-directed medication therapy. The primary outcome was a composite score of guideline-directed medical therapy, the OPS, 6 months after the end of the intervention. Secondary outcomes included active prescriptions for each individual guideline-directed medical therapy class, HF-related hospitalizations, deaths, and clinician time per patient during the intervention clinics. RESULTS: There was no significant difference between the intervention arm and usual care group in the primary outcome (OPS, 2.9; SD=2.1 versus OPS, 2.6, SD=2.1); adjusted mean difference 0.3 (95% CI, -0.1 to 0.7) or in the prespecified secondary outcomes for hospitalization and all-cause mortality for the intervention of proactive dashboard-based clinics. CONCLUSIONS: A dashboard-based clinic intervention did not improve the OPS or secondary outcomes of hospitalization and all-cause mortality. There remains a larger opportunity to better target patients and provide more intensive follow-up to further evaluate the utility of proactive dashboard-based clinics for HF management and quality improvement. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05001165.

Intrahepatic transcriptomics differentiate advanced fibrosis and clinical outcomes in adults with the Fontan circulation.

Background: The molecular mechanisms underlying Fontan associated liver disease (FALD) remain largely unknown. We aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. Methods: This retrospective cohort study included adults with the Fontan circulation at the Ahmanson/UCLA Adult Congenital Heart Disease Center. Clinical, laboratory, imaging and hemodynamic data prior to the liver biopsy were extracted from medical records. Patients were classified into early (F1-F2) or advanced fibrosis (F3-F4). RNA was isolated from formalin-fixed paraffin embedded liver biopsy samples; RNA libraries were constructed using rRNA depletion method and sequencing was performed on Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were carried out using DESeq2 and Metascape. Medical records were comprehensively reviewed for a composite clinical outcome which included decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, protein-losing enteropathy, chronic kidney disease stage 4 or higher, or death. Results: Patients with advanced fibrosis had higher serum BNP levels and Fontan, mean pulmonary artery and capillary wedge pressures. The composite clinical outcome was present in 23 patients (22%) and was predicted by age at Fontan, right ventricular morphology and presence of aortopulmonary collaterals on multivariable analysis. Samples with advanced fibrosis had 228 up-regulated genes compared to early fibrosis. Samples with the composite clinical outcome had 894 up-regulated genes compared to those without it. A total of 136 up-regulated genes were identified in both comparisons and these genes were enriched in cellular response to cytokine stimulus, response to oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-beta signaling pathway, and vasculature development. Conclusions: Patients with FALD and advanced liver fibrosis or the composite clinical outcome exhibit up-regulated genes including pathways related to inflammation, congestion, and angiogenesis. This adds further insight into FALD pathophysiology.

The effect of statins on mortality and cardiovascular disease in primary care hypertensive patients without other cardiovascular disease or diabetes.

AIMS: Studies in primary healthcare (PHC) assessing the effect of primary prevention with statins on mortality and cardiovascular disease (CVD) are scarce. This study aimed to estimate the effect of statins on all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and stroke in individuals in PHC with hypertension without CVD or diabetes. METHODS AND RESULTS: Using the Swedish PHC quality assurance register QregPV, the study included 13 193 individuals with hypertension without CVD or diabetes, who had filled a first statin prescription between 2010 and 2016, and 13 193 matched controls without a filled statin prescription at the index date. Controls were matched on sex and propensity score using clinical data and data from national registers on comorbidities, prescriptions, and socioeconomic status. The effect of statins was estimated in Cox regression models. During a median of 4.2 years of follow-up, 395 individuals in the statin group vs. 475 in the control group died, 197 vs. 232 died of cardiovascular disease, 171 vs. 191 had an MI, and 161 vs. 181 had a stroke. The treatment effect of statins was significant for all-cause mortality [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.74-0.93] and cardiovascular mortality (HR 0.85, 95% CI 0.72-0.998). Overall, no significant treatment effect of statins was seen for MI (HR 0.89, 95% CI 0.74-1.07), but there was a significant interaction with sex (P = 0.008) with decreased risk of MI for women but not for men (HR 0.66, 95% CI 0.49-0.88 vs. HR 1.09, 95% CI 0.86-1.38). CONCLUSION: Primary prevention with statins in PHC was associated with reduced risk of all-cause mortality, cardiovascular mortality, and in women, lower risk of MI.

The aim of this Swedish observational register-based study including 13 193 individuals initiating lipid-lowering medication with statins 2010­16, and 13 193 matched controls, was to study the effect of statins in people with high blood pressure without other cardiovascular disease or diabetes regarding risks for cardiovascular disease and mortality. Key findings During a median of 4.2 years of follow-up, 395 individuals in the statin group vs. 475 in the control group died, 197 vs. 232 died of cardiovascular disease, 171 vs. 191 had a myocardial infarction (MI), and 161 vs. 181 had a stroke.Primary prevention with statins was associated with 17% reduced risk of all-cause mortality, 15% reduced risk of cardiovascular mortality, and in women, 34% reduced risk of MI.

GSK3ß Inhibition Reduced Vascular Calcification in Ins2Akita/+ Mice.

Endothelial-mesenchymal transition (EndMT) drives the endothelium to contribute to vascular calcification in diabetes mellitus. In our previous study, we showed that glycogen synthase kinase-3ß (GSK3ß) inhibition induces ß-catenin and reduces mothers against DPP homolog 1 (SMAD1) to direct osteoblast-like cells toward endothelial lineage, thereby reducing vascular calcification in Matrix Gla Protein (Mgp) deficiency. Here, we report that GSK3ß inhibition reduces vascular calcification in diabetic Ins2Akita/wt mice. Cell lineage tracing reveals that GSK3ß inhibition redirects endothelial cell (EC)-derived osteoblast-like cells back to endothelial lineage in the diabetic endothelium of Ins2Akita/wt mice. We also find that the alterations in ß-catenin and SMAD1 by GSK3ß inhibition in the aortic endothelium of diabetic Ins2Akita/wt mice are similar to Mgp-/- mice. Together, our results suggest that GSK3ß inhibition reduces vascular calcification in diabetic arteries through a similar mechanism to that in Mgp-/- mice.

Regulating the cell shift of endothelial cell-like myofibroblasts in pulmonary fibrosis.

Pulmonary fibrosis is a common and severe fibrotic lung disease with high morbidity and mortality. Recent studies have reported a large number of unwanted myofibroblasts appearing in pulmonary fibrosis, and shown that the sustained activation of myofibroblasts is essential for unremitting interstitial fibrogenesis. However, the origin of these myofibroblasts remains poorly understood. Here, we create new mouse models of pulmonary fibrosis and identify a previously unknown population of endothelial cell (EC)-like myofibroblasts in normal lung tissue. We show that these EC-like myofibroblasts significantly contribute myofibroblasts to pulmonary fibrosis, which is confirmed by single-cell RNA sequencing of human pulmonary fibrosis. Using the transcriptional profiles, we identified a small molecule that redirects the differentiation of EC-like myofibroblasts and reduces pulmonary fibrosis in our mouse models. Our study reveals the mechanistic underpinnings of the differentiation of EC-like myofibroblasts in pulmonary fibrosis and may provide new strategies for therapeutic interventions.

Hypertension: sex-related differences in drug treatment, prevalence and blood pressure control in primary care.

Antihypertensive treatment is equally beneficial for reducing cardiovascular risk in both men and women. Despite this, the drug treatment, prevalence and control of hypertension differ between men and women. Men and women respond differently, particularly with respect to the risk of adverse events, to many antihypertensive drugs. Certain antihypertensive drugs may also be especially beneficial in the setting of certain comorbidities - of both cardiovascular and extracardiac nature - which also differ between men and women. Furthermore, hypertension in pregnancy can pose a considerable therapeutic challenge for women and their physicians in primary care. In addition, data from population-based studies and from real-world data are inconsistent regarding whether men or women attain hypertension-related goals to a higher degree. In population-based studies, women with hypertension have higher rates of treatment and controlled blood pressure than men, whereas real-world, primary-care data instead show better blood pressure control in men. Men and women are also treated with different antihypertensive drugs: women use more thiazide diuretics and men use more angiotensin-enzyme inhibitors and calcium-channel blockers. This narrative review explores these sex-related differences with guidance from current literature. It also features original data from a large, Swedish primary-care register, which showed that blood pressure control was better in women than men until they reached their late sixties, after which the situation was reversed. This age-related decrease in blood pressure control in women was not, however, accompanied by a proportional increase in use of antihypertensive drugs and female sex was a significant predictor of less intensive antihypertensive treatment.

Hypertension treatment in the oldest-old: focus group interviews with Swedish general practitioners.

OBJECTIVE: This study explored the considerations and experiences of Swedish General Practitioners (GPs) of hypertension treatment in patients 80 years and above. DESIGN: Qualitative design with focus group interviews. Data were analysed by qualitative content analysis. SETTING: Primary health care centres (PHCCs), both rural and urban, in the Region of Västra Götaland, Sweden. SUBJECTS: GPs and GP trainees working at PHCCs in 2019 and 2020. Five focus group interviews with 24 physicians were performed. MAIN OUTCOME MEASURES: Considerations and experiences of hypertension treatment in the oldest-old. RESULTS: Eighteen GPs and six GP trainees participated in the study. The latent content was formulated in a theme: 'The physician's decision-making in the treatment of hypertension in the oldest-old implies the inclusion of both medical and humanistic considerations.' The manifest content constituted three main categories: 'The patient characteristics' included medical condition, behavioural factors and daily life. 'The physician's role' described the GP as a professional and her/his experienced support. 'The treatment decision' considered these categories and involved risk-benefit balancing and communication. For the future, the participants proposed better guidelines for the oldest-old multimorbid patients, increased teamwork, continuous cooperation with nurses and better cooperation with hospital physicians. CONCLUSION: Hypertension care for the oldest-old was experienced as complicated by GPs, due to the need of balancing medical and humanistic considerations. The GP's clinical experience and the received support were of importance when making the treatment decision based on risk-benefit balancing and communication with the patient.Key pointsGPs experienced the task of caring for the oldest-old patients with hypertension as complicated.Patient factors like multimorbidity, polypharmacy, behavioural factors and the patient's condition of daily life were identified.Clinical experience and the experienced support at the PHCC were discussed as important for the GPs' treatment decision.Treatment decisions for the oldest-old patients with hypertension were based on risk-benefit balancing and communication with the patients.

Prediabetes and incident heart failure in hypertensive patients: Results from the Swedish Primary Care Cardiovascular Database.

BACKGROUNDS AND AIMS: The cardiovascular risk conferred by concomitant prediabetes in hypertension is unclear. We aimed to examine the impact of prediabetes on incident heart failure (HF) and all-cause mortality, and to describe time in therapeutic blood pressure range (TTR) in a hypertensive real-world primary care population. METHODS AND RESULTS: In this retrospective cohort study, 9628 hypertensive individuals with a fasting plasma glucose (FPG) in 2006-2010 but no diabetes, cardiovascular or renal disease were followed to 2016; median follow-up was 9 years. Prediabetes was defined as FPG 5.6-6.9 mmol/L, and in a secondary analysis as 6.1-6.9 mmol/L. Study outcomes were HF and all-cause mortality. Hazard ratios (HR) were compared for prediabetes with normoglycemia using Cox regression. All blood pressure values from 2001 to the index date (first FPG in 2006-2010) were used to calculate TTR. At baseline, 51.4% had prediabetes. The multivariable-adjusted HR (95% confidence intervals) was 0.86 (0.67-1.09) for HF and 1.06 (0.90-1.26) for all-cause mortality. For FPG defined as 6.1-6.9 mmol/L, the multivariable-adjusted HR were 1.05 (0.80-1.39) and 1.42 (1.19-1.70), respectively. The prediabetic group had a lower TTR (p < 0.05). CONCLUSIONS: Prediabetes was not independently associated with incident HF in hypertensive patients without diabetes, cardiovascular or renal disease. However, prediabetes was associated with all-cause mortality when defined as FPG 6.1-6.9 mmol/L (but not as 5.6-6.9 mmol/L). TTR was lower in the prediabetic group, suggesting room for improved blood pressure to reduce incident heart failure in prediabetes.

Maternal body mass index in early pregnancy is associated with overweight and obesity in children up to 16 years of age.

AIMS: Childhood obesity is an increasing public health problem. The aim of this study was to investigate the correlation between maternal body mass index in early pregnancy and body mass index in children up to the age of 16 years, and to estimate the prevalence of childhood overweight and obesity in a rural municipality in Sweden. METHODS: The study population comprised 312 pregnant women who attended the antenatal clinics in Lidköping during the year 1999 and their 319 children. Data on body mass index from antenatal clinics, child health care centres and school health care were used in linear and multinomial logistic regressions adjusted for maternal age, smoking status, and parity. RESULTS: Overweight or obesity were found in 23.0% of 16-year-olds. The correlation between maternal and child body mass index at all studied ages was positive and significant. Body mass index in 16-year-old boys showed the strongest correlation with maternal body mass index (adjusted r-square = 0.31). The adjusted relative-risk ratio for 16-year old children to be classified as obese as compared to normal weight, per 1 unit increase in maternal body mass index was 1.46 (95% confidence interval 1.29-1.65, p<0.001). Among adolescents with obesity, 37.6% had been overweight or obese at 4 years of age. CONCLUSIONS: This study confirms the correlation between maternal and child body mass index and that obesity can be established early in childhood. Further, we showed a high prevalence of overweight and obesity in children, especially in boys, in a Swedish rural municipality. This suggests a need for early intervention in the preventive work of childhood obesity, preferably starting at the antenatal clinic and in child health care centres.