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Aim: Existing data on the association between blood pressure levels and adverse cardiovascular outcomes in patients with heart failure (HF) are inconsistent. The optimal blood pressure targets for patients with HF remain uncertain. This study sought to assess the associations between blood pressure (systolic [SBP] and diastolic blood pressure [DBP]) levels and adverse cardiovascular disease (CVD) outcomes in patients with HF. Methods and results: A systematic review and meta‐analysis were conducted using MEDLINE, Embase, the Cochrane Library, and Web of Science databases up to 5 May 2023. The outcomes of interest included adverse cardiovascular events and all‐cause mortality. Pooled relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Forty‐three unique observational cohort studies, comprising 120 643 participants with HF, were included. The pooled RRs (95% CIs) for SBP thresholds of ≥140 mmHg versus <140 mmHg were 0.92 (0.83–1.01) for all‐cause mortality, 0.83 (0.67–1.04) for CVD death, and 0.98 (0.80–1.21) for HF hospitalization. The pooled RR (95% CI) for SBP thresholds of ≥160 mmHg versus <160 mmHg and all‐cause mortality was 0.67 (0.62–0.74). SBP levels below <130, <120, and <110 mmHg were each associated with an increased risk of various cardiovascular endpoints and all‐cause mortality. The pooled RR (95% CI) for DBP thresholds of ≥80 mmHg versus <80 mmHg and all‐cause mortality was 0.86 (0.67–1.10). A 10 mmHg increase in SBP or DBP was associated with a reduction in all‐cause mortality and other cardiovascular endpoints. Conclusions: The findings suggest that lower and normal baseline SBP levels (<130, <120, and <110 mmHg) may be associated with future risk of worse outcomes in patients with HF. Optimal baseline blood pressure levels for these patients may lie within the range of ≥140 mmHg for SBP. In the absence of observational studies with repeated blood pressure measurements or definitive trials evaluating optimal blood pressure targets, individualized blood pressure targets based on patients' unique circumstances are warranted in HF management. [ABSTRACT FROM AUTHOR]

The impact of blood pressure on cardiovascular disease (CVD) and mortality outcomes in older people with diabetes mellitus (DM) is not well quantified. Using a systematic review and meta-analysis of observational cohort studies, we aimed to compare the associations of blood pressure levels with cardiovascular and mortality outcomes in older people aged ≥ 65 years with or without DM. Studies were identified from MEDLINE, Embase, Web of Science, and search of bibliographies to July 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled. Forty-five unique observational cohort studies (n = 2305,189 participants) assessing the associations of systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) levels with adverse cardiovascular outcomes were included. In the general population, the pooled RRs (95% CIs) of SBP ≥ 140 vs < 140 mmHg and per 10 mmHg increase for composite CVD/MACE were 1.26 (0.96–1.64) and 1.15 (1.08–1.23), respectively. The respective estimates were 1.56 (1.04–2.34) and 1.10 (1.04–1.18) for patients with DM. SBP ≥ 130 vs < 130 mmHg was not associated with an increased risk of adverse cardiovascular outcomes in both populations. SBP < 120 vs ≥ 120 mmHg was associated with an increased risk of all cause-mortality in the general population (n = 10 studies). DBP ≥ 90 mmHg was associated with an increased risk of some adverse cardiovascular outcomes in both populations. Interaction analyses suggested similar risk of outcomes in both populations. Observational evidence suggests SBP and DBP confer similar cardiovascular and mortality risk in older adults in the general population and those with DM. A blood pressure target range of > 130/80 to < 140/90 mmHg may be optimal for patients ≥ 65 years with DM, but specific targets may need to be individualised based on patients' unique circumstances. Furthermore, findings do not support stringent blood pressure control in this population group. Definitive RCTs are needed to support these observational findings. • Blood pressure control in older people is challenging as the optimal targets are uncertain. • In the general population, SBP < 120 versus ≥ 120 mmHg is associated with an increased risk of all-cause mortality. • In diabetes, SBP ≥ 140 versus < 140 mmHg is associated with an increased risk of composite cardiovascular outcomes. • SBP ≥ 140 versus < 140 mmHg is significantly associated with an increased risk of CHD and stroke in the general population. • A 10 mmHg increase in SBP is associated with an increased risk of composite CVD/MACE. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the life expectancy following the first cardiovascular disease (CVD) event by type 2 diabetes (T2D) status and ethnicity. We used the Clinical Practice Research Datalink database in England (UK), linked to the Hospital Episode Statistics information, to identify individuals with and without T2D who survived a first CVD event between 1st Jan 2007 and 31st Dec 2017; subsequent death events were extracted from the Office for National Statistics database. Ethnicity was categorised as White, South Asian (SA), Black, or other. Flexible parametric survival models were used to estimate survival and predict life expectancy. 59,939 individuals with first CVD event were included: 7596 (12.7%) with T2D (60.9% men; mean age at event: 69.7 years [63.2 years in SA, 65.9 in Black, 70.2 in White]) and 52,343 without T2D (56.7% men; 65.9 years [54.7 in Black, 58.2 in SA, 66.3 in White]). Accounting for potential confounders (sex, deprivation, lipid-lowering medication, current smoking, and pre-existing hypertension), comparing individuals with vs without T2D the mortality rate was 53% higher in White (hazard ratio [HR]: 1.53 [95% CI: 1.44, 1.62]), corresponding to a potential loss of 3.87 (3.30, 4.44) life years at the age of 50 years in individuals with T2D. No evidence of a difference in life expectancy was observed in individuals of SA (HR: 0.82 [0.52, 1.29]; −1.36 [-4.58, 1.86] life years), Black (HR: 1.26 [0.59, 2.70]; 1.21 [-2.99, 5.41] life years); and other (HR: 1.64 [0.80, 3.39]; 3.89 [-2.28, 9.99] life years) ethnic group. Following a CVD event, T2D is associated with a different prognosis and life years lost among ethnic groups. • Limited evidence for the prognosis of individuals with cardiovascular disease (CVD) by type 2 diabetes (T2D) and ethnicity. • After first CVD, the largest life expectancy difference was in White ethnicity, (loss of 3.9 years) with vs without T2D. • Differences were non-significant in other ethnicity (3.9 years), Black (1.2 y), South Asian (-1.4 y) with vs without T2D. • Study shows the heterogeneous impact of T2D on life expectancy among individuals of different ethnicity who survived a CVD. [ABSTRACT FROM AUTHOR]

Objectives: To assess and compare the benefits and harms of intensive versus standard blood pressure (BP) control in older people with or without diabetes mellitus (DM). Design: Systematic review and meta-analysis Setting: Randomised controlled trials comparing intensive versus standard BP control, identified from MEDLINE, Embase, The Cochrane library, Web of Science and a search of bibliographies from inception till August 2022. Participants: Older people (≥65 years) with or without DM. Main outcome measures: Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for adverse vascular and safety outcomes. Results: We included six randomised controlled trials (RCTs) comprising 20,985 patients (intensive BP = 10,474 and standard BP = 10,511) with a weighted mean follow-up of 3.1 years. In the general population, the RRs (95% CIs) of intensive versus standard BP control for composite cardiovascular events or major adverse cardiovascular events (CVD/MACE), CVD mortality, coronary heart disease, stroke and heart failure were 0.71 (0.62–0.82), 0.65 (0.49–0.86), 0.75 (0.60–0.95), 0.75 (0.61–0.92) and 0.58 (0.41–0.82), respectively. Intensive BP control did not increase the risk of renal failure or serious adverse events in the general population. Two RCTs reported results for composite CVD/MACE in patients with DM with a pooled estimate of 0.85 (0.67–1.07). Conclusions: Aggregate trial evidence shows that intensive BP control (<120 to <140 mmHg) reduces the risk of adverse cardiovascular outcomes in older hypertensive patients in the general population with no increase in adverse events. Intensive BP control may confer similar benefits for older patients with DM with no evidence for harm, but this is based on limited data. PROSPERO Registration: CRD42022349791 [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase-5 inhibitors (PDE5-Is), used in the management of erectile dysfunction (ED), have potential cardioprotective benefits. The impact of PDE5-Is on reducing adverse cardiovascular outcomes in patients with diabetes mellitus (DM) and ED is uncertain. Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated if (i) the association of PDE5-Is in people with ED and DM and their risk of cardiovascular disease (CVD) and mortality and (ii) ED confers an excess risk of CVD and mortality in patients with DM compared with no DM.Methods: Studies were identified from MEDLINE, Embase, the Cochrane Library, Web of Science citation search and search of bibliographies to April 2022. Study-specific risk ratios (RRs) with 95% confidence intervals (CIs) were pooled.Results: Eighteen unique studies reported on the cardiovascular impact of ED in patients with and without DM. In the general population, the RRs (95% CIs) of ED for composite CVD/MACE, all-cause mortality, CHD and stroke were 1.43 (1.31-1.55), 1.47 (1.31-1.65), 1.59 (1.39-1.82), and 1.34 (1.15-1.56), respectively. The respective estimates were 1.68 (1.15-2.45), 1.40 (0.90-2.18), 1.41 (1.24-1.61) and 1.32 (1.09-1.60) in the diabetes population. Interaction analyses suggested similar risk in both populations. Six studies reported the cardiovascular effects of PDE5-Is in people with ED and DM. Limited RCT data showed no significant differences in the risk of major adverse cardiac event (MACE), coronary heart disease (CHD) and all-cause mortality comparing PDE5-I use with non-use: RRs (95% CIs) of 3.47 (0.17-69.19), 1.31 (0.10-16.54) and 0.35 (0.12-1.05), respectively.Conclusions: ED confers no excess risk of CVD and mortality in patients with DM compared with no DM. Limited and inadequately powered data shows no significant differences in the risk of adverse cardiovascular outcomes comparing use of PDE5-Is with non-use in patients with ED and DM. PROSPERO Registration: CRD42022324537. [ABSTRACT FROM AUTHOR]

Aim: To investigate factors associated with delays in receiving glucose‐lowering therapy in patients newly diagnosed with type 2 diabetes mellitus (T2DM), and explore the preferential order and time of intensifications. Materials and Methods: Retrospective cohort study including 120 409 adults with T2DM initiating first‐ to fourth‐line glucose‐lowering therapy in primary care between 2000 and 2018, using the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics, Office of National Statistics death registration, and 2007 Index of Multiple Deprivation data. Associations were investigated using time‐to‐event analysis. Results: The longest delays to prescription of first‐line therapy were observed in older patients, of black or other ethnicities, and with multimorbidity. People from the most deprived areas received earlier first‐line treatment than those from the least deprived areas. The majority were treated with metformin (82.4%) as the first‐line prescription, sulphonylurea (50.4%) as second‐line, dipeptidyl peptidase‐4 inhibitor (27.7%) as third‐line, and insulin (28.0%) as fourth‐line. In the past 5 years, there was an increase in prescriptions of dipeptidyl peptidase‐4‐inhibitor and sodium‐glucose transport protein‐2 inhibitor. The median time was 0.5 years for first‐line prescription, 4.1 for second‐line, 4.6 for third‐line and 4.7 for fourth‐line. After T2DM diagnosis, 25% of patients developed cardiovascular disease and non‐cardiovascular disease complications within a median time of 12‐14 years, and received intensification 5‐6 years later. Conclusions: Within the complex challenges of managing blood glucose levels and risk of additional comorbidities, future health care research and guidelines should focus on overcoming therapeutic inertia particularly at an earlier stage for older patients, from ethnic minorities and with multimorbidities. [ABSTRACT FROM AUTHOR]

Objectives. A general body of evidence suggests that low serum albumin might be associated with increased risk of adverse cardiometabolic outcomes, but findings are divergent. We aimed to quantify associations of serum albumin with the risk of type 2 diabetes (T2D), cardiovascular disease (CVD), all-cause mortality, and other adverse outcomes using a systematic review and meta-analyses of published observational cohort studies. Design. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched to January 2020. Relative risks (RRs) with 95% confidence intervals (CIs) comparing top versus bottom thirds of serum albumin levels were pooled. Results. Fifty-four articles based on 48 unique observational cohort studies comprising of 1,492,237 participants were eligible. Multivariable adjusted RRs (95% CIs) comparing the top vs bottom third of serum albumin levels were: 1.03 (0.86–1.22) for T2D; 0.60 (0.53–0.67) for CVD; 0.74 (0.66–0.84) for coronary heart disease (CHD); 0.57 (0.36–0.91) for CHD death; 0.76 (0.65–0.87) for myocardial infarction; 0.66 (0.55–0.77) for all-cause mortality; 0.71 (0.61–0.83) for venous thromboembolism; 0.65 (0.48–0.88) for cancer mortality; and 0.62 (0.46–0.84) for fracture. Heterogeneity between contributing studies of T2D was partly explained by sample sizes of studies (p for meta-regression =.035). Conclusions. Elevated levels of serum albumin are associated with reduced risk of vascular outcomes, all-cause mortality, certain cancers, and fracture. Inconsistent findings for T2D may be attributed to selective reporting by studies. Further research is needed to assess any potential causal relevance to these findings and the role of serum albumin concentrations in disease prevention. Systematic review registration: PROSPERO 2019: CRD42019125869 [ABSTRACT FROM AUTHOR]

Objectives. Circulating osteocalcin (OC), a marker which is central in bone mineralization, may be involved in the atherosclerotic process and influence the risk of developing cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of published observational evidence, to assess and quantify the associations of circulating OC (total, undercarboxylated, and carboxylated OC) with cardiovascular outcomes (clinical CVD endpoints and intermediate cardiovascular phenotypes).Design. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and reference lists of relevant studies to March 2019. Mean differences and risk ratios with 95% CIs were aggregated using random-effects models.Results. Thirty-three observational studies (prospective and retrospective cohort, case-control, and cross-sectional) with data on 21,021 unique participants were eligible. The pooled risk ratio in a comparison of extreme fourths of total OC levels was 0.98 (95% CI 0.89, 1.08) for composite CVD. Circulating total OC levels were significantly lower in patients with cardiovascular conditions compared with those without these conditions -2.58 ng/ml (95% CI -3.85, -1.32; p < .001). Prospective and cross-sectional data showed significant inverse associations between total OC and traits such as aortic or coronary calcification, coronary atherosclerosis or calcification, carotid intima-media thickness, and plaque score. There was limited data on carboxylated and undercarboxylated OC, with no evidence of associations.Conclusion. Observational evidence generally supports inverse associations of circulating total OC with risk of atherosclerotic outcomes and CVD endpoints; however, the data were mostly based on cross-sectional evaluations. Large-scale prospective data are needed. [ABSTRACT FROM AUTHOR]

Aim: To assess deintensification approaches and rates and evaluate the harm and benefits of deintensification with antidiabetic medication and other therapies among older people (≥ 65 years) with type 2 diabetes with or without cardiometabolic conditions. Methods: We identified relevant studies in a literature search of MEDLINE, Embase, Web of Science and Cochrane databases to 30 October 2018. Data were extracted on baseline characteristics, details on deintensification and outcomes, and was synthesized using a narrative approach. Results: Ten studies (observational cohorts and interventional studies) with data on 26 558 patients with comorbidities were eligible. Deintensification approaches included complete withdrawal, discontinuation, reducing dosage, conversion, or substitution of at least one medication, but the majority of studies were based on complete withdrawal or discontinuation of antihyperglycaemic medication. Rates of deintensification approaches ranged from 13.4%–75%. The majority of studies reported no deterioration in HbA1c levels, hypoglycaemic episodes, falls or hospitalizations on deintensification. On adverse events and mortality, no significant differences were observed among the comparison groups in the majority of studies. Conclusion: Available but limited evidence suggests that the benefits of deintensification outweigh the harm in older people with type 2 diabetes with or without comorbidities. Given the heterogeneity of patients with diabetes, further research is warranted on which deintensification approaches are appropriate and beneficial for each specific patient population. [ABSTRACT FROM AUTHOR]

Aims: Online patient education is a growing form of support to patients with chronic conditions, including type 2 diabetes (Type 2 DM) and cardiovascular disease (CVD). Multiple systematic reviews have been undertaken on this topic with conflicting results. We aim to explore the applications of online patient education in Type 2 DM and CVD and synthesise current evidence.Methods: A systematic review of systematic reviews was performed. Ovid Medline, EMBASE and Cochrane Database were searched between January 2005 and May 2018. Systematic reviews considering patient outcomes of online education interventions for adults with Type 2 DM and/or CVD were included. Quality assessment and data extraction was carried out in duplicate, and data combined using narrative synthesis. The PROSPERO registration number is CRD42016034018.Results: Twenty-three systematic reviews were eligible, synthesizing evidence from 87 distinct primary studies. Six reviews were high quality, nine used meta-analysis. Biological, behavioural, psychological, knowledge and self-efficacy measures are all potential targets. The outcomes most consistently showing benefits were knowledge and social support.Conclusions: Online patient education has wide ranging benefits for people with Type 2 DM or CVD. Strengths of this review include its comprehensive synthesis of the large amount of literature on this topic. [ABSTRACT FROM AUTHOR]

Background: The clinical benefit of aspirin for the primary prevention of cardiovascular disease (CVD) in diabetes remains uncertain. To evaluate the efficacy and safety of aspirin for the primary prevention of cardiovascular outcomes and all-cause mortality events in people with diabetes, we conducted an updated meta-analysis of published randomised controlled trials (RCTs) and a pooled analysis of individual participant data (IPD) from three trials. Methods: Randomised controlled trials of aspirin compared with placebo (or no treatment) in participants with diabetes with no known CVD were identified from MEDLINE, Embase, Cochrane Library, and manual search of bibliographies to January 2019. Relative risks with 95% confidence intervals were used as the summary measures of associations. Results: We included 12 RCTs based on 34,227 participants with a median treatment duration of 5.0 years. Comparing aspirin use with no aspirin, there was a significant reduction in risk of major adverse cardiovascular events (MACE)0.89 (0.83–0.95), with a number needed to treat (NNT)of 95 (95% CI 61 to 208) to prevent one MACE over 5 years average follow-up. Evidence was lacking of heterogeneity and publication bias among contributing trials for MACE. Aspirin use had no effect on other endpoints including all-cause mortality; however, there was a significant reduction in stroke for aspirin dosage ≤ 100 mg/day 0.75 (0.59–0.95). There were no significant effects of aspirin use on major bleeding and other bleeding events, though some of the estimates were imprecise. Pooled IPD from the three trials (2306 participants) showed no significant evidence of an effect of aspirin on any of the outcomes evaluated; however, aspirin reduced the risk of MACE in non-smokers 0.70 (0.51–0.96) with a NNT of 33 (95% CI 20 to 246) to prevent one MACE. Conclusions: Aspirin has potential benefits in cardiovascular primary prevention in diabetes. The use of low dose aspirin may need to be individualised and based on each individual's baseline CVD and bleeding risk. Systematic review registration PROSPERO: CRD42019122326 [ABSTRACT FROM AUTHOR]

To evaluate how sociodemographic factors influence educational modality preferences in people with cardiometabolic disease. This was a cross-sectional study performed in people with diabetes and cardiovascular disease, who completed a questionnaire to denote their previous experience and ranked preferences for different educational modalities. The questionnaire was completed by 3751 people, of whom 59% were men, median (interquartile range) age was 68 (59−76) years, and 78% were White European. In total, 73% had diabetes, 35% had heart disease, and 10% had history of stroke; the majority (83.4%) had one of these conditions. Overall preference was for one-to-one education (77% ranked first choice), and telephone education ranked the lowest. People tended to prefer modalities they had previously experienced. We highlight the importance of considering factors that could influence selection of educational modalities including age, ethnicity, gender and educational level. We anticipate this approach will aid in the design, delivery and tailoring of educational programmes that are accessible to the diverse cohort of people living with chronic diseases, including diabetes and cardiovascular disease. Given the influence of multiple demographic factors and previous experiences on expressed preferences, providers should support individuals to make informed decisions about educational interventions to maximise engagement. • Education modality preferences differ with age, ethnicity, and educational level. • One-to-one education was the most preferred and telephone the least preferred. • Targeting individual's education modality preferences may help support uptake. • A range of modalities should be available to suit the needs of diverse populations. [ABSTRACT FROM AUTHOR]

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute kidney injury, might play a role in the development of atherosclerotic cardiovascular disease (CVD). We aimed to assess the association of circulating NGAL with CVD risk. Materials and methods Plasma NGAL concentrations were measured at baseline in 5275 participants in the PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD were estimated. Results After a median follow-up of 8.3 years, 338 participants developed first CVD events. Plasma NGAL was weakly to moderately correlated with several CVD risk markers. There was a non-linear relationship between NGAL and CVD risk. In analyses adjusted for established risk factors, the hazard ratio (95% CI) for CVD in a comparison of the top quartile versus bottom quartiles 1–2 of NGAL values was 1.35 (1.05–1.75; P = 0.022), which was abrogated after additional adjustment for other potential confounders (mainly attributed to high sensitivity C-reactive protein) 1.20 (0.92–1.57; P = 0.176). The association was considerably attenuated following further adjustment for renal function 1.05 (0.79–1.40; P = 0.745). The association between NGAL and CVD risk did not vary importantly in relevant clinical subgroups. Conclusion Evidence suggests a non-linear association between NGAL and CVD risk, which is dependent on inflammation and renal function. Highlights • Increased NGAL is associated with an increased CVD risk in Caucasians. • The association is non-linear and is independent of cardiovascular risk factors. • The association is partly dependent on inflammation and renal function. [ABSTRACT FROM AUTHOR]

Background and aims We aimed to assess the association of circulating calprotectin, an inflammation-associated protein, with cardiovascular disease (CVD) risk and determine whether it improves risk prediction. Methods Plasma calprotectin measurements were made at baseline in 5290 participants in the PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD were calculated. Results After a median follow-up of 8.3 years, 339 first CVD events were recorded. Calprotectin concentration was correlated with several conventional risk factors as well as with high-sensitivity C-reactive protein (hsCRP) (r = 0.42). Calprotectin was log-linearly associated with CVD risk. The risk for CVD adjusted for conventional cardiovascular risk factors was 1.26 (95% CI, 1.13–1.41) per 1 standard deviation higher baseline log e calprotectin, and was 1.24 (95% CI, 1.11–1.39) following further adjustment for triglycerides, body mass index, and other potential confounders. The association remained present after further adjustment for hsCRP 1.15 (95% CI, 1.02–1.30). Comparing extreme quartiles of plasma calprotectin levels, the corresponding adjusted HRs for CVD were 1.96 (1.37–2.82), 1.89 (1.31–2.72), and 1.56 (1.07–2.29). The association of calprotectin with CVD risk did not vary importantly in several relevant clinical subgroups. Adding calprotectin to the Framingham CVD Risk Score was associated with a C-index change (0.0016; p =0.42) difference in −2 log likelihood ( p =0.038), IDI (0.0080; p  < 0.001), and NRI (4.03%; p =0.024). Conclusions There is a log-linear association of calprotectin concentration with risk of CVD, which may be partly dependent on hsCRP. Adding calprotectin to conventional risk factors improves CVD risk assessment using measures of reclassification and −2 log likelihood. [ABSTRACT FROM AUTHOR]