Cardiovascular Outcomes In Adults Research Articles

Cardiovascular outcomes in adults with migraine treated with eptinezumab for migraine prevention: pooled data from four randomized, double-blind, placebo-controlled studies

BackgroundPatients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. The primary objective of this analysis was to determine whether the rate of cardiovascular adverse events was higher for patients with migraine treated with the migraine-preventive eptinezumab, compared with patients receiving placebo.MethodsCardiovascular outcomes in patients with migraine were pooled across four clinical trials (phase 1b, phase 2, and two phase 3 trials) for use of eptinezumab as a preventive migraine treatment for up to 1 year. In all studies, treatment-emergent adverse events (TEAEs) that occurred after the first dose of study treatment (eptinezumab 100 mg, 300 mg, 1000 mg, or placebo) and vital signs were recorded through study completion.ResultsCardiovascular TEAEs were rare across all four clinical trials, and rates were similar between patients receiving eptinezumab and those receiving placebo. Cardiovascular TEAEs that did occur were mild or moderate in severity; there were no serious adverse events as per FDA definition. Vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) were not meaningfully different across treatment groups over the course of 56 weeks, compared to placebo. Treatment with eptinezumab did not result in significant new or changed cardiovascular medications used concomitantly compared to placebo.ConclusionsIn this post hoc analysis of four clinical trials for eptinezumab, doses of 100 mg, 300 mg, and 1000 mg (more than 3 times the highest approved dose) were not associated with clinically relevant changes in vital signs or significant changes in concomitant cardiovascular medication usage, and had low incidences of cardiovascular TEAEs, comparable to placebo.Trial registrationNCT01772524 (Study 2), 01/21/2013; NCT02275117 (Study 5), 10/27/2014; NCT02559895 (PROMISE-1), 09/25/2017; NCT02974153 (PROMISE-2), 11/28/2016

Sodium-Glucose Cotransporter 2 Inhibitors, All-Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta-Analysis and Meta-Regression.

BackgroundThis study aimed to assess the effectiveness of sodium‐glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes.Methods and ResultsWe conducted a Bayesian meta‐analysis of randomized controlled trials comparing sodium‐glucose cotransporter 2 inhibitors with placebo. We used meta‐regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty‐three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63–0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69–1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72–1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61–1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63–1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71–1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all‐cause and cardiovascular mortality. There was no association between treatment effects for all‐cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%–95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke.ConclusionsEmpagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all‐cause and cardiovascular mortality versus placebo. Treatment effects of sodium‐glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.

Meta-analysis for effect modification by sex on the associations between fine particulate matters and cardiovascular outcomes in adults

BACKGROUND AND AIM: Exposure to particulate matter with aerodynamic diameter no larger than 2.5 µm (PM2.5) can cause cardiovascular diseases (CVDs) but evidence for more vulnerable sex remains unclear in aiding clinical recommendations or public health approaches. We systematically reviewed observational studies and conduct meta-analysis to assess whether certain sex/gender is more vulnerable. METHODS: English-written studies published between 1995 and 2020 were searched from 4 databases. Population-based observation studies conducting sex subgroup analysis for the impacts of short-term or long-term ambient PM2.5 exposure on target CVDs were included. Random-effects meta-regression analyses were used to pool risk ratios (RRs) for long-term exposure and percent changes in outcomes for short-term exposure for a 10 µg/m³ increase in PM2.5 concentration. Quality of evidence of risk differences by sex was rated following the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS:Data were synthesized for 5 outcomes. The difference in RRs of all CVD mortality for a 10 µg/m³ in long-term PM2.5 concentration between men and women was not significant (1.02; 95% CI, 0.97 to 1.08). The difference in percent changes in daily mortality associated with a 10 µg/m³ increase in short-term PM2.5 concentration between men and women was not significant (-0.09; 95% CI, -0.38 to 0.19). The differences in percent changes in hospitalization/ER visits between men and women were not significant for ischemic heart disease (0.07; 95% CI, -0.83 to 0.98) and cardiac arrest (1.85; 95% CI, -1.48 to 5.30). The GRADE assessment found that there was low quality of evidence for gender difference for the risks of CVD outcomes from PM2.5 exposure. A major limitation of the studies was the lack of measuring disparities in exposure between sex groups. CONCLUSIONS:This review of observational studies indicates there is currently very limited evidence of effect modification by sex/gender for the effects of PM2.5 on CVD outcomes in adults. KEYWORDS: Environmental disparities, Particulate matter, Long-term exposure, Short-term exposure, Cardiovascular diseases

Association between sepsis survivorship and long-term cardiovascular outcomes in adults: a systematic review and meta-analysis.

We aimed to determine the association between sepsis and long-term cardiovascular events. We conducted a systematic review of observational studies evaluating post-sepsis cardiovascular outcomes in adult sepsis survivors. MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception until April 21st, 2021. Two reviewers independently extracted individual study data and evaluated risk of bias. Random-effects models estimated the pooled crude cumulative incidence and adjusted hazard ratios (aHRs) of cardiovascular events compared to either non-septic hospital survivors or population controls. Primary outcomes included myocardial infarction, stroke, and congestive heart failure; outcomes were analysed at maximum reported follow-up (from 30days to beyond 5years post-discharge). Of 12,649 screened citations, 27 studies (25 cohort studies, 2 case-crossover studies) were included with a median of 4,289 (IQR 502-68,125) sepsis survivors and 18,399 (IQR 4,028-83,506) controls per study. The pooled cumulative incidence of myocardial infarction, stroke, and heart failure in sepsis survivors ranged from 3 to 9% at longest reported follow-up. Sepsis was associated with a higher long-term risk of myocardial infarction (aHR 1.77 [95% CI 1.26 to 2.48]; low certainty), stroke (aHR 1.67 [95% CI 1.37 to 2.05]; low certainty), and congestive heart failure (aHR 1.65 [95% CI 1.46 to 1.86]; very low certainty) compared to non-sepsis controls. Surviving sepsis may be associated with a long-term, excess hazard of late cardiovascular events which may persist for at least 5years following hospital discharge.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Invited Perspective: Metal Mixtures and Child Health: The Complex Interplay of Essential and Toxic Elements.

Factors influencing home blood pressure monitor ownership in a large clinical trial

Home blood pressure monitor (HBPM) ownership prevalence and the factors that influence it are unclear. This study aimed to investigate factors associated with HBPM ownership among participants in the Treatment in Morning versus Evening (TIME) hypertension study. This study is a sub-analysis of the TIME study, a randomised trial investigating the effect of day-time versus night-time dosing of antihypertensive medication on cardiovascular outcomes in adults with hypertension. As part of the TIME study online registration process, participants were asked to indicate whether they owned an HBPM. A multivariable logistic regression model was constructed to determine factors associated with HBPM ownership. Of 21,104 randomised participants, 11,434 (54.2%) reported owning an HBPM. The mean age of all participants at enrolment was 67.7 ± 9.3 years, 12,134 (57.5%) were male, and 8892 (42.1%) reported a current or previous history of smoking. Factors associated with an increased likelihood of reporting HBPM owned include being male (OR:1.47; 95% CI 1.39–1.56) or residing in a less deprived socioeconomic region (IMD Decile 6–10) (OR:1.31; 95% CI 1.23–1.40). Participants with a history of diabetes mellitus (OR:0.74; 95% CI:0.64–0.86) or current smokers, compared to non-smokers, (OR:0.71; 95% CI:0.62–0.82) were less likely to report owning an HBPM. This study has identified important patient factors influencing HBPM ownership. Further qualitative research would be valuable to identify and explore potential patient-level barriers to engagement with self-monitoring of blood pressure.

Home blood pressure monitors owned by participants in a large decentralised clinical trial in hypertension: the Treatment In Morning versus Evening (TIME) study

Various home blood pressure monitors (HBPMs) are available to the public for purchase but only some are validated against standardised protocols. This study aimed to assess whether HBPMs owned by participants taking part in a clinical trial were validated models. The TIME study is a decentralised randomised trial investigating the effect of antihypertensive medication dosing time on cardiovascular outcomes in adults with hypertension. No HBPMs were provided to participants in this trial but patients were asked to report if they already owned one. We identified the model of HBPM reported by participants, then cross-referenced this against lists of validated HBPMs produced by dabl Educational Trust and the British and Irish Hypertension Society (BIHS). Of 21,104 participants, 10,464 (49.6%) reported their model of HBPM. 7464 (71.3%) of these participants owned a monitor that could be identified from the participants’ entry. Of these, 6066 (81.3%) participants owned a monitor listed as validated by either dabl (n = 5903) or BIHS (n = 5491). Some were listed as validated by both. 1398 (18.7%) participants owned an identifiable HBPM that lacked clear evidence of validation. 6963 (93.3%) participants owned an upper arm HBPM and 501 (6.7%) owned a wrist HBPM. Validated HBPMs had a higher median online retail price of £45.00 compared to £20.00 for HBPMs lacking clear evidence of validation. A significant number of participants own HBPMs lacking evidence of validation.

Systematic review and meta-analysis: SGLT2 inhibitors, blood pressure and cardiovascular outcomes.

ObjectiveClinical trials suggest that SGLT2 inhibitors reduce the risk of cardiovascular mortality in patients with type 2 diabetes, however the mechanism is unclear. Our objective was to test the hypothesis that blood pressure reduction is one potential mechanism underlying the observed improvements in cardiovascular outcomes with SGLT2 inhibitors.MethodsWe searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (inception-June 2019) for randomized controlled trials that reported the effect of SGLT2 inhibitors compared with placebo on cardiovascular outcomes in adults with type 2 diabetes. Two reviewers independently extracted data and assessed study quality. Random effects meta-analyses, stratified meta-analyses and meta-regressions were conducted to evaluate the association between blood pressure reduction in SGLT2 inhibitor treated patients and cardiovascular outcomes.ResultsOf 11,232 articles identified, 40 articles (n = 54,279 participants) were included. The relative risk of cardiovascular mortality was reduced by 18% with the use of SGLT2 inhibitors compared with placebo (RR 0.82; 95%CI 0.74, 0.91, I2 = 0.0%). Meta-regression analysis revealed no detectable difference in cardiovascular mortality (RR 0.93; 95%CI 0.88, 1.13, p = 0.483), 3-point major adverse cardiovascular events (p = 0.839) or congestive heart failure hospitalizations (p = 0.844) with change in mean systolic blood pressure.ConclusionsCardiovascular events are reduced in participants with type 2 diabetes treated with SGLT2 inhibitors compared with placebo. There was no significant relationship between the risk of developing adverse cardiovascular events and blood pressure reduction with SGLT2 inhibitors. There is insufficient evidence to suggest that blood pressure reduction is a significant contributor to the cardiovascular benefits observed.

Proteinuria and nocturnal blood pressure dipping in hypertensive children and adolescents.

The absence of nocturnal blood pressure dipping is associated with adverse cardiovascular outcomes in adults, and proteinuria is a risk factor for non-dipping in this population. Risk factors for non-dipping in children are largely unknown. We retrospectively identified patients aged 5-19 years who underwent 24-h ambulatory blood pressure monitoring (ABPM) from August 2018 to January 2019 and had a spot urine protein-to-creatinine ratio (PCR) within 1 year of their ABPM. Dipping was defined as ≥10% reduction in systolic and diastolic blood pressure from day to night. Multivariable logistic and linear regression models evaluated the association of proteinuria with non-dipping. Among 77 children identified, 27 (35.1%) were non-dippers. Each two-fold higher urine PCR was associated with 38% higher odds of non-dipping, after adjusting for body mass index (BMI). Higher urine PCR was also associated with a lower diastolic dipping percentage by 1.33 (95% confidence interval 0.31-2.34), after adjusting for BMI, age, and estimated glomerular filtration rate. Limitations of this study include its retrospective design and the time lapse between urine PCR and ABPM. Proteinuria appears to be associated with blood pressure non-dipping in children. This finding needs to be confirmed in prospective studies. Our study demonstrates the association of proteinuria with non-dipping of blood pressure in children. This association has been explored in adults, but to our knowledge, this is the first time it is evaluated in children referred for evaluation of elevated blood pressure. Non-dipping is a modifiable risk factor for kidney function decline and cardiovascular disease in adulthood, and thus early identification in children is important. The association between proteinuria and non-dipping in children will allow us to more readily identify those at risk, with a future focus on interventions to modify blood pressure dipping patterns.

Childhood and long-term dietary calcium intake and adult cardiovascular risk in a population with high calcium intake

The influence of dietary calcium intake in childhood on adult cardiovascular health is unknown, particularly in those with long-term high intake. To examine both linear and non-linear associations of childhood and long-term (between childhood and adulthood) dietary calcium intake with adult cardiovascular risk outcomes. A population-based prospective cohort study in Finland (n=1029, aged 3-18yearsat baseline). Dietary calcium intake was assessed in childhood (1980, baseline) and adulthood (mean of available data from 2001, 2007 and 2011). Long-term dietary calcium intake was calculated as the mean between childhood and adulthood. Outcomes were measured in 2001, 2007, and/or 2011, and the latest available data were used for analyses, including high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity (PWV), carotid artery compliance (CAC), Young's elastic modulus (YEM), and stiffness index (SI). There were no significant non-linear or linear associations between childhood or long-term dietary calcium intake with any adult cardiovascular outcomes, after adjustment for age, sex, and childhood and adulthood confounders (e.g., body mass index, systolic blood pressure, smoking, physical activity, fruit and vegetable consumption). Childhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood.

1433-P: Protective Effect of GLP-1 Receptor Agonists (GLP-1 RA) and SGLT2 Inhibitors (SGLT2i) against Adverse Cardiovascular (CV) Events in HIV and Type 2 Diabetes Mellitus (T2DM) When Compared with Metformin Alone: A National Database Study

Introduction: T2DM and HIV independently confer an increased risk of CV adverse events. We aimed to evaluate the effect of newer oral antidiabetic medications (GLP-1 RA/SGLT2i) on CV outcomes in adults with HIV and T2DM. Methods: Using a national database (IBM Explorys Solutions, IBM, Inc.), we searched for cases (HIV + T2DM patients on GLP-1 RA/SGLT2i and metformin) and controls (HIV + T2DM patients on metformin alone). We calculated comparative odds ratios (OR) and 95% confidence interval (CI) for the risk of association of GLP-1 RA/SGLT2i use and incident CV adverse events, namely myocardial infarction (MI) and acute heart failure (AHF). Results: Out of a total of 61,917,780 patients in Explorys, 29,920 had both HIV and T2DM. Patients on GLP-1 RA or SGLT2i were significantly less likely to experience an incident adverse CV event when compared to controls (Table 1). When stratified by individual drug classes (either GLP-1 RA or SGLT2i), patients on the newer antidiabetic medications were still significantly less likely to experience an adverse CV event in comparison to metformin alone (Table 1). Conclusion: GLP-1 RA and SGLT2i seem to confer a protective effect against major adverse CV events such as MI and AHF in patients with both HIV and T2DM. Disclosure O.A. Alaber: None. A.K. Chandar: None. B.A. Dahash: None. A.C. Zuzek: None. A. Rajpal: None.

Inflammation May be the Future of Cardiovascular Risk Reduction: Does Colchicine have a Current Indication?

Inflammation as a cardiovascular risk factor has attracted increasing attention . The current standard of care for decreasing the occurrence of cardiovascular events includes controlling risk factors such as hypertension and maximizing the lowering of low-density lipoprotein cholesterol (LDL-C). However, a recent study demonstrated decreased cardiovascular risk with the anti-inflammatory agent canakinumab and created more interest in decreasing cardiovascular risk by decreasing inflammation. Canakinumab is not yet approved and will undoubtedly be very expensive, so interest in an established medication such as colchicine, which is inexpensive to produce, is appropriate if evidence-based benefit is adequately confirmed. Colchicine has existing indications for gout and familial Mediterranean fever and for decreasing the incidence of postpericardiotomy syndrome. If an evidence-based benefit in decreasing cardiovascular risk can be demonstrated for colchicine, it will be of significant importance. Meta-analyses and observational studies have provided evidence to suggest that colchicine decreases cardiovascular risk because of its anti-inflammatory effects. However, randomized controlled trials (RCTs) are needed, and the recently published COLCOT (Colchicine Cardiovascular Outcomes Trial) showed definite benefit on cardiovascular outcomes in adults who had experienced a myocardial infarction within the previous 30days. Sufficient evidence now supports the use of colchicine for secondary prevention in patients at the highest cardiovascular risk who continue to have cardiovascular events despite good blood pressure control and maximum LDL-C reduction. Nevertheless, more RCTs will be necessary before widespread general use of colchicine in cardiovascular disease prevention can be recommended. The current acquisition cost issues with colchicine also need to be resolved.

Biomarkers for Prediction of Cardiovascular Events in Community-Dwelling Adults Aged 40 or Older.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and high-sensitivity C-reactive protein (hs-CRP) have been reported to be associated with cardiovascular disease (CVD). However, whether the combination of these two markers can improve the prediction of CVD is unknown.A total of 1,921 participants without CVD, aged 40 years or older, were enrolled from 2010 to 2011. Plasma Lp-PLA2 and hs-CRP were measured at baseline. Participants were subsequently followed until December 2015. We identified a total of 148 cardiovascular events (myocardial infarction, stroke, and all-cause death). Cox proportional-hazard models were used to determine the association between two independent markers and cardiovascular outcomes. The C statistic, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI) were used to determine the utility of the two markers in predicting cardiovascular risk.After adjustment for potential confounders, compared with the first quartile, hazard ratios (HRs) with 95% confidence interval (CI) for the third and fourth quartiles for Lp-PLA2 were 2.09 (1.17-3.73) and 2.62 (1.48-4.67), respectively, and HRs with 95%CI for the fourth quartile for hs-CRP was 1.78 (1.08-4.67). Compared with conventional risk factors, the combination of hs-CRP and Lp-PLA2 provided greater incremental information, and the C statistic increased by 0.013. The NRI and IDI were also statistically significant for cardiovascular events (P = 0.004 and P < 0.001, respectively).Hs-CRP and Lp-PLA2 have complementary effects in predicting cardiovascular outcomes in adults aged 40 years or older.

Effects of Nutritional Supplements and Dietary Interventions on Cardiovascular Outcomes: An Umbrella Review and Evidence Map.

The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low- to moderate-certainty evidence). Suboptimal quality and certainty of evidence. Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. None.

2017 Pediatric Hypertension Guidelines Improve Prediction of Adult Cardiovascular Outcomes.

We aimed to evaluate the consequences of the 2017 pediatric hypertension definitions, compared with the 2004 pediatric hypertension definitions on the prevalence of hypertension and to assess the performance of these 2 sets of guidelines in predicting adult hypertension, metabolic syndrome, and left ventricular hypertrophy (LVH). This longitudinal study consisted of 3940 children (47% male; ages 3-18 years) who came from the Bogalusa Heart Study with 36-year follow-up since childhood. Hypertension was identified in 7% and 11% as defined in the 2004 and 2017 guidelines, respectively. The 2004 and 2017 guidelines demonstrated similar associations with adulthood hypertension, metabolic syndrome, and LVH. However, the proportion of children identified as having hypertension who developed adult LVH increased from 12% when defined by the 2004 guidelines to 19% when defined by the 2017 guidelines. Overall, the 329 (8%) children who were reclassified to higher blood pressure categories by the 2017 guidelines were more likely than their propensity score-matched normotensive counterparts to develop hypertension, metabolic syndrome, and LVH in later life, whereas 38 (1%) children who were reclassified to lower blood pressure categories by the 2017 guidelines had similar cardiometabolic outcomes to their propensity score-matched normotensive counterparts. Hence, children who were reclassified to higher blood pressure categories based on 2017 guidelines were at increased risk of developing hypertension, metabolic syndrome, and LVH in later life. The 2017 guidelines identified a group of children with adverse metabolic profile and cardiometabolic outcomes, whose cardiovascular risk seemed to be underestimated using the 2004 guidelines.

Efficacy of Vitamin D on Chronic Heart Failure Among Adults.

Vitamin D deficiency commonly occurs in chronic heart failure. Whether additional vitamin D supplementation can be beneficial to adults with chronic heart failure remains unclear. We conducted a meta-analysis to derive a more precise estimation. PubMed, Embase, and Cochrane databases were searched on September 8, 2016. Seven randomized controlled trials that investigated the effects of vitamin D on cardiovascular outcomes in adults with chronic heart failure, and comprised 592 patients, were included in the analysis. Compared to placebo, vitamin D, at doses ranging from 2,000IU/day to 50,000IU/week, could not improve left ventricular ejection fraction (Weighted mean difference, WMD=3.31, 95% confidence interval, CL=-0.93 to 7.55, P<0.001, I2=92.1%); it also exerts no beneficial effects on the 6 minute walk distance (WMD=18.84, 95% CL=-24.85 to 62.52, P=0.276, I2=22.4%) and natriuretic peptide (Standardized mean difference, SMD=-0.39, 95% confidence interval CL=-0.48 to 0.69, P<0.001, I2=92.4%). However, a dose-response analysis from two studies demonstrated an improved left ventricular ejection fraction with vitamin D at a dose of 4,000IU/day (WMD=6.58, 95% confidence interval CL=-4.04 to 9.13, P=0.134, I2=55.4%). The results showed that high dose vitamin D treatment could potentially benefit adults with chronic heart failure, but more randomized controlled trials are required to confirm this result.

Preterm Birth as a Risk Factor for Metabolic Syndrome and Cardiovascular Disease in Adult Life: A Systematic Review and Meta-Analysis

To determine if preterm birth is associated with components of the metabolic syndrome in adult life. A structured literature search was performed using PubMed. All comparative studies reported metabolic and cardiovascular outcomes in adults (≥18years of age) born preterm (<37weeks of gestation) compared with adults born at term (37-42weeks of gestation) and published through March 2018 were included. The major outcomes assessed were body mass index, waist circumference, waist-to-hip ratio, fat mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), 24-hour SBP, 24-hour DBP, endothelium-dependent brachial artery flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, fasting glucose and insulin, Homeostasis Model Assessment-Estimated Insulin Resistance Index, and lipid profiles. Quality appraisal was performed using a modified version of the Newcastle-Ottawa scale. A meta-analysis was performed for comparable studies which reported sufficient data. Forty-three studies were included, including a combined total of 18 295 preterm and 294 063 term-born adults. Prematurity was associated with significantly higher fat mass (P=.03), SBP (P<.0001), DBP (P<.0001), 24-hour SBP (P<.001), and 24-hour DBP (P<.001). Furthermore, preterm-born adults presented higher values of fasting glucose (P=.01), insulin (P=.002), Homeostasis Model Assessment-Estimated Insulin Resistance Index (P=.05), and total cholesterol levels (P=.05) in comparison with adults born at term, in random effect models. No statistically significant difference was found between preterm and term-born adults for the other outcomes studied. Preterm birth is strongly associated with a number of components of the metabolic syndrome and cardiovascular disease in adult life.

Risk Markers and Intermediate Outcomes in Research and Clinical Practice.

In adult cardiovascular disease, researchers have introduced a plethora of new imaging and biomarkers in hopes that these novel risk markers will either improve risk prediction for individuals, lend biological plausibility to modifying underlying behaviors or more aggressively treating traditional risk factors like blood pressure and lipids, or offer insights into pathophysiology that is amenable to drug therapy.1 One of these novel factors is retinal vessel diameters, which predict future cardiovascular outcomes, at least in women.2–4 In this issue of Pediatrics , Kochli et al5 examine retinal vessel diameters in children. They posit that physical activity, BMI, and blood pressure affect retinal vessel diameters, which reflect early signs of microvascular disease, which, in turn, leads to adult cardiovascular outcomes. With this article, we provide an opportunity to consider when novel risk factors are useful either in making clinical decisions or in research. Pediatric clinicians often use risk markers, by themselves or in combination with … Address correspondence to Alan E. Simon, MD, Environmental Influences on Child Health Outcomes Program, National Institutes of Health, 6011 Executive Blvd, Suite 325, Room 316, Rockville, MD 20852. E-mail: alan.simon{at}nih.gov

Liraglutide and cardiovascular outcomes in adults with overweight or obesity: A post hoc analysis from SCALE randomized controlled trials.

The cardiovascular safety of liraglutide, a glucagon‐like peptide‐1 receptor agonist approved for weight management at a dose of 3.0 mg, was evaluated post hoc using data from 5908 participants in 5 randomized, double‐blind, placebo‐controlled clinical trials. Participants were randomized to liraglutide or a comparator group (placebo or orlistat). The objective was to evaluate whether cardiovascular risk was increased with liraglutide treatment. The primary composite outcome of this time‐to‐event analysis was the first occurrence of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. These cardiovascular events were adjudicated prospectively for three of the trials and retrospectively for two trials by an event adjudication committee. The primary outcome was analyzed using a Cox proportional hazards model, stratified by trial. With liraglutide 3.0 mg, 8 participants had positively adjudicated cardiovascular events (1.54 events/1000 person‐years) compared to 10 participants in the comparators group (3.65 events/1000 person‐years). The hazard ratio for liraglutide 3.0 mg compared to comparators was 0.42 (95% confidence interval, 0.17‐1.08). In this analysis, liraglutide 3.0 mg treatment was not associated with excess cardiovascular risk. However, the wide confidence intervals and retrospective adjudication of events in two of the trials are limitations of the analysis.

Heritability and risks associated with early onset hypertension: multigenerational, prospective analysis in the Framingham Heart Study

Objective To determine the role of early onset versus late onset hypertension as a risk factor for hypertension in offspring and cardiovascular death.Design Multigenerational, prospective cohort study.Setting Framingham Heart Study.Participants...