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Abstract Background Patients with overweight/obesity and type 2 diabetes are encouraged to lose weight, but not all losing weight gain better cardiovascular health, especially old adults. The change in skeletal muscle mass (SMM) could be the key that explains the heterogenous cardiovascular effects of weight loss. This study aims to assess whether the cardiovascular effects of weight loss vary for those gaining skeletal muscle along with weight loss. Methods The old adults with overweight/obesity and type 2 diabetes in the Look AHEAD study having muscle measurement from dual‐energy X‐ray absorptiometry were included. Based on the weight change (WC) and SMM change (SMMC) between baseline and the 4‐year follow‐up, participants were allocated into three groups—weight gain (WG) group, weight loss with muscle loss (WL‐ML) group and weight loss with muscle gain (WL‐MG) group. Cox proportional hazards regression was performed to evaluate the cardiovascular risk of those gaining or losing SMM with weight loss compared with those gaining weight. Among the participants with weight loss, the ratio of SMMC/WC was calculated, and the association of SMMC/WC with primary cardiovascular outcome was assessed. Results A total of 491 participants were included in the study with an average age of 64.56 ± 3.81 years old. A total of 47.0% were male and 49.9% were from the intensive lifestyle intervention arm. Based on their WC and SMMC, 43 were assigned to the WG group, 373 to the WL‐ML group and 75 to the WL‐MG group. Over a follow‐up of almost 10 years, 97 participants encountered the primary endpoint. The WG group had the highest incidence of 25.59%, the WL‐MG group had the lowest incidence of 9.33% and the WL‐ML group had 21.18% (P = 0.040). In the fourth adjusted Cox model, the WL‐MG group achieved significantly decreased odds of the primary endpoint compared with the WG group (hazard ratio [HR] 0.33, 95% confidence interval [CI] [0.12, 0.87], P = 0.026), whilst the WL‐ML group did not (HR 0.91, 95% CI [0.47, 1.78], P = 0.670). Among the participants with weight loss, when SMMC/WC reached around 50%, this HR soared to approximately two‐fold. Conclusions The participants gaining SMM along with weight loss achieved the lowest odds of adverse cardiovascular events, whilst those who lost SMM along with weight loss had comparable cardiovascular risk with those gaining weight. The more muscle lost during weight loss, the greater the harm. The cardiovascular effects of weight loss were modulated by whether the participants gained SMM meanwhile losing weight.

Abstract Aims This study aimed to assess the effect of blood pressure (BP) index, in terms of level and variability, on the progression of cardiovascular and renal diseases in patients with both heart failure (HF) and chronic kidney disease (CKD). Methods and results The study involved patients with HF and CKD from the database of the Chronic Renal Insufficiency Cohort (CRIC) study. The study endpoint includes the following: (i) primary endpoint, including cardiovascular disease (CVD) events, renal events, and all‐cause death; (ii) CVD events; (iii) renal events; and (iv) all‐cause death. Among 3939 participants in the CRIC study, a total of 382 patients were included. The duration of the follow‐up was 6.3 ± 2.7 years, the age was 60.2 ± 8.9 years, and 57.6% were male. BP index included 20 indicators in relation to BP level and variability, 4 of which were analysed including baseline systolic BP (SBP), standard deviation of SBP, coefficient of variation of diastolic BP (DBP CV), and average real variability of pulse pressure. In the Cox regression analysis after adjustment, baseline SBP was significant for the risk of primary endpoint [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.03–1.44, P = 0.02] and renal events (HR 1.54, 95% CI 1.22–1.95, P

Abstract Background The triglyceride-glucose (TyG) index is a reliable surrogate marker of insulin resistance (IR). However, whether the TyG index has prognostic value in patients with moderate to severe aortic stenosis (AS) remains unclear. Methods This study enrolled 317 patients with moderate to severe AS at the First Affiliated Hospital of Sun Yat-Sen University. The patients were grouped according to the cut-off value of the TyG index. Cox regression with Firth’s penalized maximum likelihood method and restricted cubic splines regression were conducted to assess the association between the TyG index and all-cause mortality. The added value of the TyG index included in the traditional risk factors model for outcome prediction was also analyzed. Results Among 317 patients (mean age 67.70 years, 62.8% male), there was 84 all-cause mortality during a median 38.07 months follow-up. After fully adjusting for confounders, a per-unit increase in the TyG index was associated with a 62% higher all-cause mortality risk (HR 1.622, 95% CI 1.086–2.416, p = 0.018). The restricted cubic splines regression model revealed a linear association between the TyG index and the risk of all-cause mortality (p for nonlinearity = 0.632). The addition of the TyG index in the basic risk model has an incremental effect on the prediction of mortality [C-statistic change from 0.755 to 0.768; continuous net reclassification improvement (95% CI): 0.299 (0.051–0.546), p = 0.017; integrated discrimination improvement: 0.017 (0.001–0.033), p = 0.044]. Conclusions Higher IR assessed by the TyG index was associated with a higher risk of all-cause mortality in patients with moderate and severe AS.

Abstract Aims/introduction Weight variability is associated with cardiovascular outcomes in diabetic patients. However, whether the guideline‐recommended intensive lifestyle intervention (ILI) will affect this association in overweight or obese adults with diabetes is not well established. Materials and Methods In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, the associations of 4 year weight variability measured by variability independent of the mean (VIM) with major adverse cardiovascular event (MACE) and secondary outcomes in ILI and diabetes support & education (DSE) arm were evaluated. Results During a median follow‐up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23‐fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51–3.30). Compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were associated with higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20–2.95), all‐cause mortality (HR 3.19; 95% CI 1.75–5.82), and myocardial infarction (HR 1.95; 95% CI 1.12–3.37) in the DSE arm. Conclusions Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm. Therefore, a guideline‐recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without worrying about the effect of weight fluctuations.

Introduction Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain.Methods and analysis Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group.Ethics and dissemination Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations.Trial registration number ChiCTR2200063191.

Background: Few studies have examined the relationship between the fluctuation of heart rate control over time and cardiovascular outcomes in patients with atrial fibrillation. Our study sought to evaluate the independent association between time in target range (TIR) of resting heart rate and cardiovascular outcomes in the AFFIRM (Atrial Fibrillation Follow-Up Investigation of Rhythm Management) study. Methods: Target range of resting heart was defined as less than 80 beats per minute (bpm) for both rate and rhythm control groups. Time in target range was estimated over the first 8 months of follow-up using Rosendaal interpolation method. The association between TIR of resting heart rate and cardiovascular outcomes was estimated using adjusted Cox proportional hazards regression models. Results: Time in target range of resting heart rate (months 0 through 8) was 71 ± 34% in the rate control group and 83 ± 27% in the rhythm control group. Each 1-SD increase in TIR of resting heart rate was significantly associated with lower risk of major adverse cardiovascular events after full adjustment for demographics, medical history and history of prior heart surgery, as well as all-cause mortality. Conclusions: Time in target range of resting heart rate independently predicts the risk of cardiovascular outcomes in patients with atrial fibrillation. Long-term maintenance of heart rate on target is of great importance for patients with atrial fibrillation.

BackgroundChronically high blood pressure (HBP) is a known risk factor for cardiovascular diseases. We measured the intensity of hypertensive exposure in young adults and calculated its prognostic significance for subclinical atherosclerosis in middle age.MethodsThe Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5,115 healthy black and white Americans who were 18–30 years old at baseline (1985–1986). The intensity of hypertensive exposure was calculated as the area under the curve (mm Hg × years) from baseline to year 15. Coronary artery calcium (CAC) was identified at years 15, 20, and 25, and intima-media thickness (IMT) was identified at year 20.ResultsAt baseline, the mean age was 40.1 years; 55.1% of participants were women, and 46.5% were black. After adjustment, cumulative systolic BP (SBP) was positively associated with CAC [hazard ratio (HR) = 1.23 (1.14, 1.32)] and IMT [β = 0.022 (0.017, 0.028)]. For CAC, the C-statistic for cumulative SBP was 0.643 (0.619, 0.667); compared to baseline SBP, the net reclassification index (NRI) of cumulative SBP was 0.180 (0.115, 0.256) and the integrated discrimination improvement (IDI) was 0.023 (0.012, 0.036). For IMT, the C-statistic for cumulative SBP was 0.674 (0.643, 0.705), the NRI was 0.220 (0.138, 0.305), and the IDI was 0.008 (0.004, 0.0012).ConclusionGreater intensity of hypertensive exposure in early adulthood is associated with subclinical atherosclerosis in middle age and provides better prognostic value than baseline BP for early cardiovascular risk.

Background Currently available guidelines contain conflicting recommendations on the management of blood pressure (BP) in patients with diabetes mellitus (DM). Therefore, it is necessary to appraise the guidelines and summarize the agreements and differences among recommendations. Methods Four databases and the websites of guideline organizations were searched for guidelines regarding BP targets and thresholds for pharmacologic therapy in DM patients, and the included guidelines were appraised with the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. Results In 6,498 records identified, 20 guidelines met our inclusion criteria with 64.0% AGREE II scores (interquartile range, 48.5% to 72.0%). The scores of the European and American guidelines were superior to those of the Asian guidelines (both adjusted P140 mm Hg (10 guidelines, 50%) and diastolic BP thresholds >90 mm Hg (nine guidelines, 45%). The tiny minority of the guidelines provided the relevant recommendations regarding the lower limit of official BP targets and the ambulatory BP monitoring (ABPM)/home BP monitoring (HBPM) targets and thresholds in DM patients. Conclusion The lower official BP targets (

Background The associations of time‐averaged cumulative blood pressure (BP) from midlife to late life with microvasculature expressed as retinal vessel diameters is not well studied. The aim of this study was to evaluate the association of cumulative systolic BP and diastolic BP (DBP) with retinal vessel calibers, focusing on race differences. Methods and Results The analysis included 1818 adults from the ARIC (Atherosclerosis Risk in Communities) study attending the fifth visit (2011–2013; age 77±5 years, 17.1% Black participants). Time‐averaged cumulative BPs were calculated as the sum of averaged BPs from adjacent consecutive visits (visits 1–5) indexed to total observation time (24±1 years). Summarized estimates for central retinal arteriolar equivalent and central retinal venular equivalent at the fifth visit represent average retinal vessel diameters. The arteriole:venule ratio was calculated. We tested for effect modification by race. Results from multiple linear regression models suggested that higher time‐averaged cumulative DBP (β [95% CI] per 1‐SD increase: −1.78 [−2.53, −1.02], P

Summary: Background: We aimed to assess whether the cardiovascular effects of intensive lifestyle intervention (ILI) vary for those who can maintain the lower body weight after weight loss through ILI. Methods: In the secondary analysis of the Look AHEAD trial, we identified the status of weight loss for the participants in the ILI arm based on body weight time in range (TIR). These participants were allocated to three groups according to body weight TIR: 0% (n = 727), >0% to 50% (n = 656), and >50% to 100% (n = 811). For each group, cardiovascular outcomes were compared with matched participants receiving diabetes support & education (DSE) using 1:1 propensity score matching and Cox regression. Findings: During a median of 9·5 years of follow-up, participants with TIR of >50% to 100% can effectively maintain their body weight after weight loss through ILI; participants with TIR of 0% or >0% to 50% do not achieve or maintain weight loss. Compared with the corresponding matched participants in the DSE arm, participants with TIR of >50% to 100% in the ILI arm had a 45% lower risk of the primary outcome (HR 0·55, 95% CI 0·40–0·76), and no significant effects were found on the risk of the primary outcome in participants with TIR of 0% (HR 1·12, 95% CI 0·86–1·46) or >0% to 50% (HR 1·14, 95% CI 0·85–1·52). Interpretation: In adults with overweight/obesity and type 2 diabetes, ILI might help in lowering the risk of cardiovascular events when the lower body weight is maintained after weight loss. Funding: None.

Abstract Background Echocardiography (echo) is the primary imaging modality for infective endocarditis (IE). However, the recommendations on timing and mode selection for transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) vary across guidelines, which can be confusing for clinical decision makers. In this case, we aim to appraise the quality of recommendations by appraising the quality of various guidelines. Methods A search of guidelines containing recommendations for the appropriate use of echo in adult IE patients published in English between 2007 and 2019 was conducted. The APPRAISAL OF GUIDELINES FOR RESEARCH & EVALUATION II (AGREE II) instrument was applied independently by two reviewers to assess the integrated quality of the identified guidelines. The recommendations of concern are extracted from related chapters. Results A total of 9 guidelines met the criteria, with AGREE II scores ranging from 36 to 79%, and the domain of “stakeholder involvement” received the lowest score. The most contentious issue is whether a follow-up TEE is mandatory in uncomplicated native valve IE with an initial positive TTE. Conflicting recommendations are presented with a low evidence level based on little evidence. Conclusions In general, the recommendations proposed in the 9 identified guidelines on the appropriate use of echo are satisfying. The guideline quality score can be taken into account by the clinicians when evaluating the recommendations for clinical decisions. Additional studies with high evidence level should be conducted on the most controversial issues of whether a subsequent TEE is mandatory in uncomplicated native valve IE with an initial positive TTE.

Background There is a paucity of evidence regarding the association between visit‐to‐visit blood pressure variability and residual cardiovascular risk. We aimed to provide relevant evidence by determining whether high systolic blood pressure (SBP) variability in the optimal SBP levels still influences the risk of cardiovascular disease. Methods and Results We studied 7065 participants (aged 59.3±5.6 years; 44.3% men; and 82.9% White) in the ARIC (Atherosclerosis Risk in Communities) study with optimal SBP levels from visit 1 to visit 3. Visit‐to‐visit SBP variability was measured by variability independent of the mean in the primary analysis. The primary outcome was the major adverse cardiovascular event (MACE), defined as the first occurrence of all‐cause mortality, coronary heart disease, stroke, and heart failure. During a median follow‐up of 19.6 years, 2691 participants developed MACEs. After multivariable adjustment, the MACE risk was higher by 21% in participants with the highest SBP variability (variability independent of the mean quartile 4) compared with the lowest SBP variability participants (variability independent of the mean quartile 1) (hazard ratio, 1.21; 95% CI, 1.09–1.35). The restricted cubic spline showed that the hazard ratio for MACE was relatively linear, with a higher variability independent of the mean being associated with higher risk. These association were also found in the stratified analyses of participants with or without hypertension. Conclusions In adults with optimal SBP levels, higher visit‐to‐visit SBP variability was significantly associated with a higher risk of MACE regardless of whether they had hypertension. Therefore, it may be necessary to further focus on the visit‐to‐visit SBP variability even at the guideline‐recommended optimal blood pressure levels.

Background The association between blood pressure control and clinical outcomes is unclear among patients with heart failure with preserved ejection fraction. Both too high and too low of systolic blood pressure (SBP) have been reported to be related to poor clinical prognosis. This study aimed to assess the association between time in SBP target range and adverse clinical events among patients with heart failure with preserved ejection fraction. Methods and Results This study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, a randomized clinical trial that compared the efficacy and safety of spironolactone in patients with heart failure with preserved ejection fraction. Time in target range (TTR) was calculated using linear interpolation, with the target range of SBP defined as 110 to 130 mm Hg. The association between TTR with adverse outcomes was estimated using multivariable Cox regression to adjust for multiple confounders. Participants with greater TTR were younger, more likely to be White, had less comorbidities, and lower body mass index. After adjusting for multiple covariates including mean SBP, 1‐SD increment (38.3%) of TTR was significantly associated with a decreased risk of primary composite end point (hazard ratio [HR], 0.81 [0.73–0.90]), as well as a lower risk of all‐cause mortality (HR, 0.81 [0.73–0.90]), cardiovascular death (HR, 0.78 [0.68–0.90]), and heart failure hospitalization (HR, 0.85 [0.74–0.97]). Results were similar when participants were categorized by TTR groups. Subgroup analyses showed that the associations were more significant in young people than in the old (Pinteraction=0.028). Conclusions In patients with heart failure with preserved ejection fraction, greater time in SBP target range was statistically associated with a decreased risk of cardiovascular outcomes and mortality events beyond blood pressure level, especially among younger patients.

Objective: In our present study, our objective was to appraise guidelines on antithrombotic therapy in atrial fibrillation post-percutaneous coronary intervention and to explore the differences in treatment practices for better informed decision-making. Methods: We searched for English language guidelines published between January 2000 and December 2020 at MEDLINE, Embase and websites of guideline organizations. Guidelines with recommendations on antithrombotic regimens for patients with AF undergoing PCI were included. Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was applied to assess guidelines. The reporting of conflicts of interest (COI) was evaluated separately by the RIGHT (Reporting Item for Practice Guidelines in Healthcare) checklist as supplementary items. Results: Sixteen guidelines were included, among which 13 (81.25%) were considered as ‘recommended’ and 1 (6.25%) as ‘unrecommended.’ The average scores of guidelines ranged from 55% to 88% (70% as good quality). Among the 6 domains of AGREE II, scope and purpose (84%) and editorial independence(87%) were considered to be the fields in which CPGs performed best, evidenced by the highest mean AGREE II scores. The domains in which the reviewed CPGs received the lowest mean scores were stakeholder involvement (63%) and applicability (58%). The intraclass correlation coefficient scores were excellent in each domain. The overall quality of the selected CPGs was optimal, with the highest score in domain ‘scope and purpose’, and the lowest score in the domain ‘applicability.’ The reporting of COI was satisfactory. Conclusions: For the recommendations on antithrombotic strategies, guidelines with high AGREE II scores still exist discrepancy on the timing and selection. Current guidance documents on the treatment vary in methodological rigor and recommendations are not always consistent.

Glycemic variability was found associated with left ventricular structure and function in type 2 diabetes. But it is still unclear that whether the greater visit-to-visit fasting glucose (FG) variability in young adulthood among the community population is associated with cardiac function alteration and cardiac remodeling at midlife. The community-based prospective cohort study of Coronary Artery Risk in Young Adult (CARDIA) recruited young participants at the baseline age of 18–30 years during the period of 1985–1986 (Year 0). FG was measured at Year 0, 2, 10, 15, 20, and 25. The echocardiographic evaluation of cardiac structure and function was conducted at year 25. A total of 2,600 young adults mean (SD) aged at 24.9 years (3.6) of which 57.3% were women and 46.7% were African Americans had been included in the study. After multivariable adjusted, higher SD of mean FG (SDFG) is associated with lower early peak diastolic septal mitral annular velocity (e') (β [SE], −0.214 [0.080], P < 0.01) and higher E/e' (β [SE], 0.307 [0.094], P < 0.01), and higher coefficient of variation of the mean FG (CVFG) is also associated with lower e' (β [SE], −0.141[0.066], P < 0.05) and higher E/e' (β [SE], 0.204 [0.078], P < 0.01). The higher average real variation of mean FG (ARVFG) is associated with higher E/e' (β [SE], 0.178 [0.085], P < 0.05) and higher left ventricular mass index (LVMI) (β [SE], 1.240 [0.618], P < 0.05). The higher FG variability in young adulthood is associated with the subclinical change of left ventricular (LV) diastolic function at midlife.

Background: Systolic or diastolic blood pressure (BP) variability is associated with an increased risk of cardiovascular events. We assessed whether BP variability measured by mean arterial pressure (MAP) was associated with increased risk of heart failure (HF) and death in individuals with or without hypertension.Methods: We evaluated 9,305 Atherosclerosis Risk in Communities (ARIC) study participants with or without hypertension and calculated BP variability based on MAP values from visit 1 to 4 [expressed as standard deviation (SD), average real variability (ARV), coefficient of variation (CV), and variability independent of the mean (VIM)]. Multivariate-adjusted Cox regression model and restricted cubic spline curve were used to evaluate the associations of MAP variability with all-cause mortality and HF.Results: During a median follow-up of 16.8 years, 1,511 had an HF event and 2,903 died. Individuals in the highest quartile of VIM were both associated with a 21% higher risk of all-cause mortality [hazard ratio (HR), 1.21; 95% CI, 1.09–1.35] and HF (HR, 1.21; 95% CI, 1.04–1.39) compared with the lowest quartile of VIM. Cubic spline curves reveal that the risk of deaths and HF increased with MAP variability when it reached a higher level. Results were similar in individuals with normotension (all-cause mortality: HR, 1.30; 95% CI, 1.09–1.55; HF, HR, 1.49; 95% CI, 1.12–1.98).Conclusions: In individuals with or without hypertension, greater visit-to-visit MAP variability was associated with a higher risk of all-cause mortality and HF, indicating that the BP variability assessed by MAP might be a potential risk factor for HF and death.

AimTo determine whether long-term intensity of glycemic exposure (IGE) during young adulthood is associated with multiple target organs function at midlife independent of single fasting glucose (FG) measurement.MethodsWe included 2,859 participants, aged 18–30 years at Y0, in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. IGE was calculated as the sum of (average FG of two consecutive examinations × years between the examinations) over 25 years. Target organs function was indicated by cardiac structure, left ventricular (LV) systolic function, LV diastolic function, coronary artery calcium (CAC), and urine albumin-to-creatinine ratio (UACR) at Y25. We evaluated the associations between IGE with target organs function using linear regression models and estimated the associations between IGE with numbers of organs involved (0, 1, or ≥ 2 organs) using multinomial logistic regression models.ResultsA 1-SD increment of IGE was significantly associated with worse target organs function after multivariable adjustment: left ventricular mass (β [SE], 5.468 [1.175]); global longitudinal strain (β [SE], 0.161 [0.071]); E/e’ ratio (β[SE], 0.192 [0.071]); CAC score (β [SE], 27.948 [6.116]); and log UACR (β [SE], 0.076 [0.010]). Besides, IGE was independently associated with having ≥ 2 organs involved in both overall population (OR [95% CI], 1.48 [1.23, 1.41], P < 0.001) and subgroups stratified by diabetes at Y25.ConclusionHigher intensity of glycemic exposure during young adulthood was independently associated with subclinical alterations of target organs function at midlife. Our findings highlight the importance of early screening and management of IGE in youth.

Background: The elevated blood pressure (BP) at midlife or late-life is associated with cardiovascular disease and death. However, there is limited research on the association between the BP patterns from middle to old age and incident coronary heart disease (CHD) and death.Methods: A cohort of the Atherosclerosis Risk in Communities (ARIC) Study enrolled 9,829 participants who attended five in-person visits from 1987 to 2013. We determined the association of mid- to late-life BP patterns with incident CHD and all-cause mortality using multivariable-adjusted Cox proportional hazards models.Results: During a median of 16.7 years of follow-up, 3,134 deaths and 1,060 CHD events occurred. Compared with participants with midlife normotension, the adjusted hazard ratio for all-cause mortality and CHD was 1.14 (95% CI, 1.04–1.25) and 1.28 (95% CI, 1.10–1.50) in those with midlife hypertension, respectively. In further analyses, compared with a pattern of sustained normotension from mid- to late-life, there was no significant difference for the risk of incident death (HR, 1.15; 95% CI, 0.96–1.37) and CHD (HR, 1.33; 95% CI, 0.99–1.80) in participants with a pattern of midlife normotension and late-life hypertension with effective BP control. A higher risks of death and CHD were found in those with pattern of mid- to late-life hypertension with effective BP control (all-cause mortality: HR, 1.24; 95% CI, 1.08–1.43; CHD: HR, 1.65; 95% CI 1.30–2.09), pattern of midlife normotension and late-life hypertension with poor BP control (all-cause mortality: HR, 1.27; 95% CI, 1.12–1.44; CHD: HR, 1.53; 95% CI, 1.23–1.92), and pattern of mid- to late-life hypertension with poor BP control (all-cause mortality: HR, 1.49; 95% CI, 1.30–1.71; CHD: HR, 1.87; 95% CI, 1.48–2.37).Conclusions: The current findings underscore that the management of elderly hypertensive patients should not merely focus on the current BP status, but the middle-aged BP status. To achieve optimal reductions in the risk of CHD and death, it may be necessary to prevent, diagnose, and manage of hypertension throughout middle age.

Background The influences of low‐carbohydrate diets in cardiovascular disease are controversial. Few studies have examined the relationship of carbohydrate intake and risk of incident atrial fibrillation (AF). We aimed to evaluate the association between carbohydrate intake and the risk of incident AF in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results We included 13 385 participants (age, 54.2±5.8 years; 45.1% men and 74.7% white) who completed a dietary questionnaire at baseline (1987–1989) in the ARIC Study. The primary outcome was incident AF, which was identified by ECG performed during study examinations, hospital discharge codes, and death certificates. We used multivariable Cox hazard regression models to assess the association between carbohydrate intake and incident AF. We further explored the effects of specific food source (animal versus plant based) used to replace carbohydrate intake in the low‐carbohydrate intake setting. During a median follow‐up of 22.4 years, 1808 cases (13.5%) of AF occurred. The hazard ratio for incident AF associated with a 1‐SD (9.4%) increase in carbohydrate intake as a percentage of energy intake was 0.82 (95% CI, 0.72–0.94), after adjustment for traditional AF risk factors and other diets factors. Results were similar when individuals were categorized by carbohydrate intake quartiles (hazard ratio, 0.64; 95% CI, 0.49–0.84; comparing extreme quartiles). No association was found between the type of protein or fat used to replace the carbohydrate and risk of incident AF. Conclusions Low‐carbohydrate diets were associated with increased risk of incident AF, regardless of the type of protein or fat used to replace the carbohydrate.