Discordance between mean glucose and time in range in relation to HbA1c in individuals with type 1 diabetes: results from the GOLD and SILVER trials.

AIMS/HYPOTHESIS: Previous studies have shown that individuals with similar mean glucose levels (MG) or percentage of time in range (TIR) may have different HbA1c values. The aim of this study was to further elucidate how MG and TIR are associated with HbA1c. METHODS: Data from the randomised clinical GOLD trial (n=144) and the follow-up SILVER trial (n=98) of adults with type 1 diabetes followed for 2.5 years were analysed. A total of 596 paired HbA1c/continuous glucose monitoring measurements were included. Linear mixed-effects models were used to account for intra-individual correlations in repeated-measures data. RESULTS: In the GOLD trial, the mean age of the participants (± SD) was 44±13 years, 63 (44%) were female, and the mean HbA1c (± SD) was 72±9.8 mmol/mol (8.7±0.9%). When correlating MG with HbA1c, MG explained 63% of the variation in HbA1c (r=0.79, p<0.001). The variation in HbA1c explained by MG increased to 88% (r=0.94, p value for improvement of fit <0.001) when accounting for person-to-person variation in the MG-HbA1c relationship. Time below range (TBR; <3.9 mmol/l), time above range (TAR) level 2 (>13.9 mmol/l) and glycaemic variability had little or no effect on the association. For a given MG and TIR, the HbA1c of 10% of individuals deviated by >8 mmol/mol (0.8%) from their estimated HbA1c based on the overall association between MG and TIR with HbA1c. TBR and TAR level 2 significantly influenced the association between TIR and HbA1c. At a given TIR, each 1% increase in TBR was related to a 0.6 mmol/mol lower HbA1c (95% CI 0.4, 0.9; p<0.001), and each 2% increase in TAR level 2 was related to a 0.4 mmol/mol higher HbA1c (95% CI 0.1, 0.6; p=0.003). However, neither TIR, TBR nor TAR level 2 were significantly associated with HbA1c when accounting for MG. CONCLUSIONS/INTERPRETATION: Inter-individual variations exist between MG and HbA1c, as well as between TIR and HbA1c, with clinically important deviations in relatively large groups of individuals with type 1 diabetes. These results may provide important information to both healthcare providers and individuals with diabetes in terms of prognosis and when making diabetes management decisions.

Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON-HF and PARADIGM-HF trials.

BACKGROUND: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes. METHODS: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF. RESULTS: Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: - 0.24%, 95% CI - 0.33 to - 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan. CONCLUSIONS: Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711.

Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction.

AIMS: Patients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on 'apparent resistant hypertension' in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril-valsartan with valsartan. METHODS AND RESULTS: In this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795). 'Apparent resistant hypertension' was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. 'Apparent mineralocorticoid receptor antagonist (MRA)-resistant' hypertension was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril-valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6-19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7-14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05-1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril-valsartan vs. valsartan in patients with apparent resistant hypertension [-4.8 (-7.0 to -2.5) and 3.9 (-6.6 to -1.3) mmHg] and apparent MRA-resistant hypertension [-8.8 (-14.0 to -3.5) and -6.3 (-12.5 to -0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril-valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30-2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18-5.89). CONCLUSION: Sacubitril-valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA. CLINICAL TRIAL REGISTRATION: PARAGON-HF: ClinicalTrials.gov Identifier NCT01920711.

The majority of people with type 1 diabetes and multiple daily insulin injections benefit from using continuous glucose monitoring: An analysis based on the GOLD randomized trial (GOLD-5).

AIM: To identify responders to continuous glucose monitoring (CGM) in relation to reductions in HbA1c and percentage of time spent in hypoglycaemia after initiation of CGM for individuals with type 1 diabetes treated with multiple daily insulin injections. MATERIALS AND METHODS: We analysed data from 142 participants in the GOLD randomized clinical trial. We evaluated how many lowered their HbA1c by more than 0.4% (>4.7 mmol/mol) or decreased the time spent in hypoglycaemia over 24 hours by more than 20 or 30 minutes, and which baseline variables were associated with those improvements. RESULTS: Lower reduction of HbA1c was associated with greater reduction of hypoglycaemia (r = -0.52; P < .0001). During CGM, 47% of participants lowered their HbA1c values by more than 0.4% (>4.7 mmol/mol) than with self-measurement of blood glucose, and 47% decreased the time spent in hypoglycaemia by more than 20 minutes over 24 hours. Overall, 78% either reduced their HbA1c by more than 0.4% (>4.7 mmol/mol) or the time spent in hypoglycaemia by more than 20 minutes over 24 hours, but only 14% improved both. Higher HbA1c, a lower percentage of time at less than 3.0 or 3.9 mmol/L, a lower coefficient of variation (CV) and a higher percentage of time above 13.9 mmol/L (P = .016) were associated with greater HbA1c reduction during CGM. The variables associated with a greater reduction of time in hypoglycaemia were female sex, greater time with glucose levels at less than 3.0 mmol/L, higher CV, and higher hypoglycaemia confidence as evaluated by a hypoglycaemic confidence questionnaire. CONCLUSION: The majority of people with type 1 diabetes managed by multiple daily insulin injections benefit from CGM; some experienced reduced HbA1c while others reduced the time spent in hypoglycaemia. These factors need to be considered by healthcare professionals and decision-makers for reimbursement and diabetes guidelines.

Blood pressure and mortality in patients with type 2 diabetes and a recent coronary event in the ELIXA trial.

BACKGROUND: The relationship between blood pressure and mortality in type 2 diabetes (T2DM) is controversial, with concern for increased risk associated with excessively lowered blood pressure. METHODS: We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline blood pressure and all-cause mortality in 5852 patients with T2DM and a recent acute coronary syndrome (ACS) who participated in the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial. Risk of death was assessed in Cox models adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, brain natriuretic peptide (BNP), urine albumin/creatinine ratio, treatment allocation and prior coronary revascularization. RESULTS: Although overall there was no significant association between systolic blood pressure (SBP) and mortality (hazard ratio per 10 mmHg lower SBP 1.05 (95% CI 0.99-1.12) P = 0.10), lower SBP was significantly associated with higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13 (95% CI 1.04-1.22) P = 0.002) in 2325 patients with additional CVD (index ACS+ at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure). In 3527 patients with only the index ACS no significant association was observed (hazard ratio per 10 mmHg lower SBP 0.95 (0.86-1.04) P = 0.26; P for interaction 0.005). CONCLUSIONS: The association between blood pressure and mortality was modified by additional CVD history in patients with type 2 diabetes and a recent coronary event. When blood pressures measured after an acute coronary event are used to assess the risk of death in patients with type 2 diabetes, the cardiovascular history needs to be taken into consideration. Trial registration ClinicalTrials.gov number NCT01147250, first posted June 22, 2010.

Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain.

AIMS: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. METHODS: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25-29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. RESULTS: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. - 22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05). CONCLUSION: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons. Trial registration ClinicalTrials.gov identifier NCT 01049737.

Diastolic orthostatic hypertension and cardiovascular prognosis in type 2 diabetes: a prospective cohort study.

BACKGROUND: In patients with type 2 diabetes, the prognostic impact of an orthostatic rise in blood pressure is not known. Therefore, the aim of this study was to determine the prognostic implications of the diastolic orthostatic blood pressure response in a cohort of patients with type 2 diabetes. We also evaluated associations between different orthostatic blood pressure responses and markers of subclinical cardiovascular organ damage. METHODS: Office blood pressures were measured in the sitting and in the standing position in 749 patients with type 2 diabetes who participated in the CARDIPP study (Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care). Diastolic orthostatic hypertension was defined as a rise of diastolic blood pressure ≥10 mmHg and diastolic orthostatic hypotension was defined as a drop of diastolic blood pressure ≥10 mmHg. Recruitment took place between the years 2005-2008, and patients were followed until any of the primary outcome events (cardiovascular death or hospitalization for either myocardial infarction or stroke) occurred or until December 31st, 2014. Measurements of aortic pulse wave velocity and of carotid intima-media thickness were performed at base-line. RESULTS: Diastolic orthostatic hypertension was found in 140 patients (18.7 %) and was associated with significantly lower risk of cardiovascular events (crude hazard ratio compared with patients with normal systolic and diastolic orthostatic blood pressure response: 0.450, 95 % C.I. 0.206-0.987, P = 0.046). Diastolic orthostatic hypotension was found in 31 patients (4.1 %) and was associated with higher values for aortic pulse wave velocity and carotid intima-media thickness, compared with patients with normal systolic and diastolic orthostatic blood pressure response. CONCLUSIONS: Diastolic orthostatic hypertension is common in patients with type 2 diabetes, and may be a novel marker for decreased cardiovascular risk in these patients.

Treatment Satisfaction and Well-Being With CGM in People With T1D: An Analysis Based on the GOLD Randomized Trial.

BACKGROUND: The GOLD trial demonstrated that continuous glucose monitoring (CGM) in people with type 1 diabetes (T1D) managed with multiple daily insulin injections (MDI) improved not only glucose control but also overall well-being and treatment satisfaction. This analysis investigated which factors contributed to improved well-being and treatment satisfaction with CGM. METHODS: The GOLD trial was a randomized crossover trial comparing CGM versus self-monitored blood glucose (SMBG) over 16 months. Endpoints included well-being measured by the World Health Organization-Five Well-Being Index (WHO-5) and treatment satisfaction by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) as well as glucose metrics. Multivariable R2-decomposition was used to understand which variables contributed most to treatment satisfaction. RESULTS: A total of 139 participants were included. Multivariable analyses revealed that increased convenience and flexibility contributed to 60% (95% confidence interval [CI] = 50%-69%) of the improvement in treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire change version [DTSQc]) observed with CGM, whereas perceived effects on hypoglycemia and hyperglycemia only contributed to 6% (95% CI = 2%-11%) of improvements. Significant improvements in well-being (WHO-5) by CGM were observed for the following: feeling cheerful (P = .025), calm and relaxed (P = .024), being active (P = .046), and waking up fresh and rested (P = .044). HbA1c reductions and increased time in range (TIR) were associated with increased treatment satisfaction, whereas glycemic variability was not. HbA1c reduction showed also an association with increased well-being and increased TIR with less diabetes-related distress. CONCLUSIONS: While CGM improves glucose control in people with T1D on MDI, increased convenience and flexibility through CGM is of even greater importance for treatment satisfaction and patient well-being. These CGM-mediated effects should be taken into account when considering CGM initiation.

Associations between fruit consumption and home blood pressure in a randomly selected sample of the general Swedish population.

Frequent fruit consumption has been associated with lower office blood pressure. Less is known about associations between fruit consumption and home blood pressure. Our aim was to study the correlation between consumption of specific fruits and home blood pressure in a large randomly selected study population. The main outcome was systolic home blood pressure. Home blood pressure measurements were performed with calibrated oscillometric meters during seven consecutive days. Means for all available measurements were used. Validated food frequency questionnaires were used for estimating frequency of fruit consumption. The specified fruits were bananas, apples/pears and oranges/citrus fruit. Complete case analysis regarding fruit consumption, office- and home blood pressure measurements and other relevant variables was performed in 2283 study participants out of 2603 available. Multivariable linear regression analysis was performed. There were statistically significant associations between consumption of all fruit types and lower systolic home blood pressure unadjusted (p for trend; bananas, apples/pears and oranges/citrus fruit p < .001). The numerical differences between most and least frequent consumption of fruit were for bananas -2.7 mm Hg, apples/pears -3.9 mm Hg and for oranges/citrus fruit -3.4 mm Hg. When adjusted for covariates, both consumption of apples/pears and oranges/citrus fruit had an independent statistically significant association with lower blood pressure (p = .048 resp. p = .009). Future controlled interventional studies are needed to evaluate the effect of specific fruit on home blood pressure.

NT-proBNP as a predictor of death and cardiovascular events in patients with type 2 diabetes.

Existing risk prediction scores based on clinical and laboratory variables have been considered inaccurate in patients with Type 2 Diabetes Mellitus (T2DM). Circulating concentrations of natriuretic peptides have been used to aid in the diagnosis and to predict outcomes in heart failure. However, there is a growing body of evidence for the use of natriuretic peptides measurements, mainly N-terminal pro-B-type natriuretic peptide (NT-proBNP), as a tool in risk stratification for individuals with T2DM. Studies have demonstrated the ability of NT-proBNP to improve outcomes prediction when incorporated into multivariate models. More recently, evidence has emerged of the discriminatory power of NT-proBNP, demonstrating, as a single variable, a similar and even superior ability to multivariate risk models for the prediction of death and cardiovascular events in individuals with T2DM. Natriuretic peptides are synthesized and released from the myocardium as a counter-regulatory response to increased cardiac wall stress, sympathetic tone, and vasoconstriction, acting on various systems and affecting different biological processes. In this article, we present a review of the accumulated knowledge about these biomarkers, underscoring the strength of the evidence of their predictive ability for fatal and non-fatal outcomes. It is likely that, by influencing the functioning of many organs, these biomarkers integrate information from different systems. Although not yet recommended by guidelines, measurement of natriuretic peptides, and particularly NT-proBNP, should be strongly considered in the risk stratification of individuals with T2DM.

Effect of liraglutide on markers of insulin production in persons with type 2 diabetes treated with multiple daily insulin injections.

In this post-hoc analysis of data from a randomised clinical trial, we compared the effect of liraglutide to placebo on markers of insulin secretion in persons with type 2 diabetes treated with multiple daily insulin injections. Liraglutide increased insulin secretion, measured by C-peptide, by 19% after 24 weeks of treatment. CLINICAL TRIAL REGISTRATION: EudraCT 2012-001941-42.

Risk factors, mortality trends and cardiovasuclar diseases in people with Type 1 diabetes and controls: A Swedish observational cohort study.

Background: Historically, the incidence of cardiovascular disease and mortality in persons with Type 1 diabetes (T1D) has been increased compared to the general population. Contemporary studies on time trends of mortality and cardiovascular disease are sparse. Methods: In this observational study, T1D persons were identified in the Swedish National Diabetes Registry (n=45,575) and compared with matched controls from the general population (n=220,141). Incidence rates from 2002 to 2019 were estimated with respect to mortality and cardiovascular disease in persons with T1D overall and when stratified for prevalent cardiovascular and renal disease relative to controls. Findings: Mean age in persons with T1D was 32.4 years and 44.9% (20,446/45,575) were women. Age- and sex- adjusted mortality rates declined over time in both groups but remained significantly higher in those with T1D compared to controls during 2017-2019, 7.62 (95% CI 7.16; 8·08) vs. 2.23 (95% CI 2.13; 2.33) deaths per 1,000 person years. Myocardial infarction, heart failure and stroke decreased over time in both groups, with persistent excess risks in the range of 3.4-5.0 times from 2017 to 2019 in those with T1D. T1D persons ≥45 years without previous renal or cardiovascular complications had standardized mortality rates similar or even lower than controls 5.55 (4.51; 6.60) vs.7.08 (6.75; 7.40) respectively in the last time period. Interpretation: Excess mortality persisted over time in persons with T1D, largely in patients with cardiorenal complications. Improved secondary prevention with a focus on individualized treatment is needed to close the gap in mortality for individuals with T1D. Funding: This study was financed by grants from the ALF-agreement, NovoNordisk Foundation and the Swedish Heart and Lung Foundation.

Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With MDI: An Analysis Based on the GOLD Randomized Trial (GOLD 8).

BACKGROUND: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. METHOD: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. RESULTS: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 (P = .16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment (P < .001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. CONCLUSION: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.

Cardiac Structure and Function Across the Spectrum of Aldosteronism: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Aldosterone production and mineralocorticoid receptor activation are implicated in myocardial fibrosis and cardiovascular events. METHODS: Cardiac structure and function were assessed in 4547 participants without prevalent heart failure (HF) in the ARIC study (Atherosclerosis Risk in Communities), with echocardiography, aldosterone, and plasma renin activity measurement (2011-2013). Subjects were characterized by plasma renin activity as suppressed (≤0.5 ng/mL per hour) or unsuppressed (>0.5 ng/mL per hour). Cross-sectional relationships with cardiac structure and function, and longitudinal relationships with outcomes (HF hospitalization; HF and all-cause death; HF, death, myocardial infarction, and stroke; and incident atrial fibrillation) were assessed. Models were adjusted for demographic and anthropometric characteristics and additively, for blood pressure and antihypertensives. RESULTS: Evidence of primary aldosteronism physiology was prevalent (11.6% with positive screen) and associated with echocardiographic parameters. Renin suppression was associated with greater left ventricular mass, left ventricular volumes, and left atrial volume index, and a lower E/A ratio (adjusted P<0.001 for all). Higher aldosterone was associated with greater left ventricular mass and lower global longitudinal strain and lateral E'. The highest tertile of aldosterone was associated with a hazard ratio of 1.37 (95% CI, 1.06-1.77; 5.5-year follow-up) for incident atrial fibrillation relative to the lowest. Renin suppression was associated with HF (hazard ratio, 1.34 [95% CI, 1.05-1.72]; 7.3-year follow-up), although these relationships did not remain statistically significant after additional adjustment for hypertension. CONCLUSIONS: Renin suppression and aldosterone excess, consistent with primary aldosteronism pathophysiology, were associated with cardiac structural and functional alterations and may represent an early target for mitigation of fibrosis with mineralocorticoid receptor antagonists.

Importance of NT-proBNP and conventional risk factors for prediction of death in older adults with and without diabetes mellitus- A report from the Atherosclerosis Risk in Communities (ARIC) study.

In this community-based cohort of 5861 individuals followed for median 7.2 years, the discriminatory ability of NT-proBNP alone in predicting mortality was similar to that of multiple conventional markers of risk in people without diabetes. In people with diabetes, NT-proBNP alone discriminated risk of mortality better than conventional risk factors.

Hemodynamic responses to In-Bed Cycle Exercise in the acute phase after moderate to severe stroke: A randomized controlled trial.

Hemodynamic responses to exercise in the acute phase after moderate to severe stroke have remained poorly investigated. The aim of this randomized controlled study, in which 52 (32 women) patients with moderate to severe stroke were randomized to three weeks of 20 minutes in-bed cycle exercise 5 days per week or to usual care, was to explore the systolic blood pressure (SBP) response to exercise and to evaluate the impact of the intervention on the resting and post-test systolic and diastolic blood pressures and heart rate, and on the systolic blood pressure response to exercise. We found that resting SBP decreased from baseline to post-intervention in both the intervention group (147.7 ± 18.1 mmHg to 125.3 ± 17.1 mmHg, P < .001) and in the control group (147.8 ± 23.7 mmHg to 131.4 ± 14.8 mmHg, P < .001) without a significant difference between the groups (interaction P = .308). However, there was a significant difference (interaction P = .010) regarding how Δ SBP (change in SBP from pre-test to post-test) changed from baseline to post-intervention. In the intervention group, Δ SBP increased from -1.0 ± 15.0 mmHg to 8.5 ± 9.4 mmHg, P = .009, whereas in the control group, Δ SBP decreased from 7.1 + 10.9 mmHg to 4.5 + 11.8 mmHg, P = .395. We conclude that patients randomized to in-bed cycle exercise seemed to normalize their blood pressure response to exercise to a larger extent than patients in the control group.

Relationships between cardiovascular risk factors and white-coat hypertension diagnosed by home blood pressure recordings in a middle-aged population.

OBJECTIVE: To study risk in white-coat hypertension (WCH) by measurement of coronary artery calcium score (CACS), carotid--femoral pulse-wave velocity (PWV) and carotid plaques. METHODS: Cross-sectional population-based cohort with randomized selection of participants from Linköping, Sweden. An Omron m10-IT oscillometric device was used for clinic and home blood pressures (HBP) in the morning and evening for 1 week. RESULTS: We recruited 5029 middle-aged and mainly defined WCH as SBP at least 140 mmHg and/or DBP at least 90 mmHg with HBP less than 135/85 mmHg. There were 2680 normotensive participants and 648 had WCH after exclusion of treated participants. More women (59.5%) than men (42.8%, P < 0.001) had WCH. We found higher prevalence of CACS greater than 100 compared with less than 100 (12.4 vs. 7.2%, P < 0.001), PWV (11.5 ±â€Š1.5 vs. 10.4 ±â€Š1.3 m/s, P < 0.001) and a higher prevalence of one or more carotid plaques (59.5 vs. 48%, P < 0.001) in participants with WCH than in normotension. Participants with WCH also had more dyslipidemia and higher glucose levels. Normotensive women scored lower on nervousness than women with WCH (P = 0.022). After matching of 639 participants with WCH to normotensive participants according to age, gender and systolic HBP the prevalence of a high CACS (12.1 vs. 8.6%, P = 0.003,) PWV (11.0 ±â€Š0.068 vs. 11.5 ±â€Š0.068 m/s, estimated marginal means ±â€ŠSE, P < 0.001 by ANOVA) but not more carotid plaques (59.5 vs. 55.6%, P = 0.23), remained in the participants with WCH compared with the matched normotensive participants. CONCLUSION: WCH is particularly common in middle-aged women, and it displays metabolic dysfunction and increased prevalence of arteriosclerotic manifestations in both genders. As markers of increased cardiovascular risk were present also after matching normotensive and WCH participants according to systolic HBP, age and gender, the presence of WCH signals an increased cardiovascular risk burden that is not fully explained by elevated BP levels at home.

NT-proBNP versus routine clinical risk factors as a predictor of cardiovascular events or death in people with dysglycemia - A brief report from the ORIGIN trial.

In patients with diabetes and cardiovascular or renal comorbidities, circulating levels of the N-terminal fragment of prohormone B-type natriuretic peptide (NT-proBNP) have similar discriminatory ability as multivariate models for prediction of cardiovascular events or death. We validated this finding in patients with dysglycemia not selected for co-existing cardiorenal diseases.

Resistance to antihypertensive treatment and long-term risk: The Atherosclerosis Risk in Communities study.

More stringent blood pressure (BP) goals have led to greater prevalence of apparent resistant hypertension (ARH), yet the long-term prognostic impact of ARH diagnosed according to these goals in the general population remains unknown. We assessed the prognostic impact of ARH according to contemporary BP goals in 9612 participants of the Atherosclerosis Risk in Communities (ARIC) study without previous cardiovascular disease. ARH, defined as BP above goal (traditional goal <140/90 mmHg, more stringent goal <130/80 mmHg) despite the use of ≥3 antihypertensive drug classes or any BP with ≥4 antihypertensive drug classes (one of which was required to be a diuretic) was compared with controlled hypertension (BP at goal with 1-3 antihypertensive drug classes). Cox regression models were adjusted for age, sex, race, study center, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, and diabetes. Using the traditional BP goal, 133 participants (3.8% of the treated) had ARH. If the more stringent BP goal was instead applied, 785 participants (22.6% of the treated) were reclassified from controlled hypertension to uncontrolled hypertension (n = 725) or to ARH (n = 60). Over a median follow-up time of 19 years, ARH was associated with increased risk for a composite end point (all-cause mortality, hospitalization for myocardial infarction, stroke, or heart failure) regardless of whether traditional (adjusted HR 1.50, 95% CI: 1.23-1.82) or more stringent (adjusted HR 1.43, 95% CI: 1.20-1.70) blood pressure goals were applied. We conclude that in patients free from cardiovascular disease, ARH predicted long-term risk regardless of whether traditional or more stringent BP criteria were applied.

Sustained Intensive Treatment and Long-term Effects on HbA1c Reduction (SILVER Study) by CGM in People With Type 1 Diabetes Treated With MDI.

OBJECTIVE: Continuous glucose monitoring (CGM) reduces HbA1c and time spent in hypoglycemia in people with type 1 diabetes (T1D) treated with multiple daily insulin injections (MDI) when evaluated over shorter time periods. It is unclear to what extent CGM improves and helps to maintain glucose control, treatment satisfaction, diabetes distress, hypoglycemic concerns, and overall well-being over longer periods of time. RESEARCH DESIGN AND METHODS: The GOLD trial was a randomized crossover trial performed over 16 months of CGM treatment in people with T1D treated with MDI. People completing the trial (n = 141) were invited to participate in the current SILVER extension study in which 107 patients continued CGM treatment over 1 year along with the support of a diabetes nurse every 3 months. RESULTS: The primary end point of the change in HbA1c over 1.0-1.5 years of CGM use compared with previous self-monitoring of blood glucose during GOLD showed a decrease in HbA1c of 0.35% (95% CI 0.19-0.50, P < 0.001). Time spent in hypoglycemia <3.0 mmol/L (54 mg/dL) and <4.0 mmol/L (72 mg/dL) decreased from 2.1% to 0.6% (P < 0.001) and from 5.4% to 2.9% (P < 0.001), respectively. Overall well-being (World Health Organization 5-item well-being index, P = 0.009), treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire, P < 0.001), and hypoglycemic confidence (P < 0.001) increased, while hypoglycemic fear (Hypoglycemia Fear Survey-Worry, P = 0.016) decreased and diabetes distress tended to decrease (Problem Areas in Diabetes Scale, P = 0.06). From randomization and screening in GOLD, HbA1c was lowered by 0.45% (P < 0.001) and 0.68% (P < 0.001) after 2.3 and 2.5 years, respectively. CONCLUSIONS: The SILVER study supports beneficial long-term effects from CGM on HbA1c, hypoglycemia, treatment satisfaction, well-being, and hypoglycemic confidence in people with T1D managed with MDI.