Relative Risk Of Cardiovascular Events Research Articles

Assessment of cardiovascular risk in women with premature ovarian failure

BACKGROUND: Premature ovarian failure is a common disease that affects quality of life and cardiovascular risk in young women. AIM: To assess the relative risk of cardiovascular events in patients with primary and secondary premature ovarian failure. MATERIAL AND METHODS: The study included three groups of patients comparable in age: the first — women with primary premature ovarian failure at the age of 39.8±4.3 years; the second — women with secondary premature ovarian failure, age 40.1±4.1 years; the third was the control group at the age of 40.3±3.9 years, there were 133 people in each group. The cardiovascular profile (smoking status, metabolic health, lipid profile, glucose level, blood pressure, pulse and cardiovascular history) of patients with premature ovarian failure was analyzed. Identification of relationships between the studied signs (increase in waist circumference, increase in systolic blood pressure 140 mm Hg, increase in diastolic blood pressure 90 mm Hg, dyslipidemia, arterial hypertension, arrhythmia, coronary heart disease, diabetes mellitus, metabolic syndrome) carried out by calculating the odds ratio and relative risk. The 10-year risk of developing cardiovascular diseases was also calculated using the SCORE2 scale. RESULTS: Patients with both primary and secondary premature ovarian failure had a higher relative risk of developing cardiovascular events compared with healthy women. The 10-year risk of developing cardiovascular events according to the SCORE2 scale was statistically significantly increased in women with premature ovarian failure compared to the control group. In patients with primary failure it was 9.4% (confidence interval 6–14%; p=0.018), in patients with secondary failure — 7.6% (confidence interval 4–14%; p=0.023), and in the control group — 5.1% (confidence interval 3–14%; p=0.039). CONCLUSION: Patients with premature ovarian failure have a higher cardiovascular risk compared to a group of healthy women.

EVALUATION OF INFLAMMATORY BIOMARKERS IN CHRONIC KIDNEY DISEASE ASSOCIATED WITH CARDIOVASCULAR DISEASE IN A TERTIARY CARE HOSPITAL OF WEST BENGAL

Introduction: Factors responsible for cardiovascular disease (CVD) become operational from the early course of CKD and are spread over the entire spectrum of it. The relative risks of cardiovascular events are inversely related to the estimated glomerular ltration rate (eGFR). A patient with CKD is more likely to die from CVD rather than CKD which denotes high burden of CVD in subpopulation and need for early intervention to reduce mortality. Generally in the population, early CKD, atherosclerotic disease is predominant cardiovascular disease but as the CKD progresses the burden of non-atherosclerotic disease increases.Aims:To evaluate relation of Inammatory Biomarkers (IB) in CKD patients with and without ECG and Echocardiography evaluated LVH and IHD with hypokinetic or dyskinetic wall motion with specic ECG changes in KPCMCH. Materials and method: This study was conducted 18 months at KPC medical college and hospital jadavpur, kolkata-72. 100 patients were included in this study. Result: Our study showed that, majority number of patients were Abnormal [64 (87.7%)] in with Echo LVH compared to [16(59.3%)] without Echo LVH it was statistically signicant (p=0.0016) and we also found that, majority number of patients were Abnormal [64(87.7%)] in with Echo LVH compared to [17 (63.0%)] it was statistically signicant (p=0.0272). Conclusion:We concluded that the frequency and types of cardiovascular diseases associated with different stages of CKD, traditional risk factors in CVD associated with various stages of CKD

Coronary heart disease in patients with human immunodeficiency virus infection

According to the World Health Organization, more than 38 million people are carriers of the human immunodeficiency virus (HIV). The relative risk of cardiovascular events in patients with HIV infection is 1.52 times higher than those without it. An HIV-positive status is associated with a 50% increased risk of acute myocardial infarction. The mechanisms of CVD development caused by HIV activity are not fully understood, and the contribution of traditional risk factors cannot fully explain such a high potential for coronary heart disease (CHD) in patients with HIV infection. Data suggest that HIV-associated chronic inflammation and immune system activation may lead to progressive endothelial dysfunction and vascular damage. The pathogenesis of atherosclerosis and, consequently, CHD in HIV infection is extremely versatile and poorly studied. The key mechanisms in HIV-associated CHD include the effect of HIV proteins on immunocompetent cells and vascular endothelium, immunodeficiency, translocation of microorganisms from the gut, and chronic inflammation with platelet activation. Despite considerable progress in understanding HIV-associated cardiovascular disease, many unresolved questions remain. Even with effective viral suppression, inflammation and immune dysregulation appear to increase the risk of cardiovascular complications. The lack of large-scale clinical studies on the prevention and treatment of cardiovascular disease in HIV is very important. Nevertheless, some important features should be considered in the management of patients with HIV infection.

A comprehensive risk score incorporating 24-hour ambulatory blood pressure.

Although ambulatory blood pressure (BP) monitoring is required for the proper diagnosis and management of hypertension, conventional office BP has not yet been replaced by ambulatory BP in the currently available risk charts. For the current analysis, we selected 9,024 participants from the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcomes (IDACO) aged ≥40 to <80 years with a baseline ambulatory BP recording including ≥6 daytime and ≥3 nighttime reading. Given the age range of the analyzed participants, we focused on systolic BP as a risk factor. Time-to-event analysis was conducted using the Cox model, and the 5-year risk was computed using the established formula used in the Heart “OMics” in AGEing (HOMAGE) study (J Am Heart Assoc 2017:e005231). Age at enrolment averaged 59.0 years, 48.2% women, and average 24 h systolic BP was 125.8 mmHg. The median number of ambulatory readings recorded over 24 h and the median follow-up of the cohort was 55 (ranging across cohorts from 37 to 80) and 13.9 years (from 4.0 to 23.3 years), respectively. All endpoints—composite cardiovascular endpoints, cardiovascular mortality, and total mortality—were positively associated with 24-h systolic BP, being on antihypertensive drug treatment at baseline, age, male sex, smoking, a history of cardiovascular disease, having diabetes, and non-drinking alcohol (P≤0.0032). Total mortality was inversely associated with body mass index and total cholesterol, whereas the composite cardiovascular endpoint and cardiovascular mortality were not. None of the endpoints was associated with Non-Asian versus Asian ethnicity (P≥0.31). Based on these findings, we constructed a risk score for each endpoint. The reference category was assigned to young (40–44 years old), women, no smoker, body mass index between 25–29 kg/m2, total serum cholesterol between 5.17–6.20 mmol/L, no diabetes, no history of cardiovascular disease, drinker, and 24-h ambulatory BP of <110 mmHg. The relative risk of cardiovascular events among the quintile of the scores in the participants was clearly separated, and estimated versus observed outcomes across the quintile groups demonstrated similar trends with showing good agreement. Although replication has not yet been fully achieved, the current risk calculator can be a valuable tool for healthcare providers as well as people for introducing ambulatory BP monitoring to the early detection and intervention for the general population and treatment naïve patients with high BP.

Cost-Effectiveness, Burden of Disease and Budget Impact of Inclisiran: Dynamic Cohort Modelling of a Real-World Population with Cardiovascular Disease.

ObjectiveWe aimed to estimate the cost-effectiveness, burden of disease and budget impact of inclisiran added to standard-of-care lipid-lowering therapy in the real-world secondary cardiovascular prevention population in Switzerland.MethodsAn open-cohort Markov model captured event risks by sex, age and low-density lipoprotein cholesterol based on epidemiological and real-world data. Low-density lipoprotein cholesterol reduction with add-on inclisiran was based on trial results and translated to meta-analysis-based relative risks of cardiovascular events. Unit costs for 2018 were based on publicly available sources, adopting a Swiss healthcare system perspective. Price assumptions of Swiss francs (CHF) 500 and CHF 3,000 per dose of inclisiran were evaluated, combined with uptake assumptions for burden of disease and budget impact. The assessment of cost-effectiveness used a discount rate of 3% per year. We performed deterministic and probabilistic sensitivity analyses, and extensive scenario analyses.ResultsPatients treated with inclisiran gained a 0.291 qualityadjusted life-year at an incremental cost per QALY gained of CHF 21,107/228,040 (life-long time horizon, discount rate 3%) under the lower/higher price. Inclisiran prevented 1025 cardiovascular deaths, 3425 acute coronary syndrome episodes, and 1961 strokes in 48,823 patients ever treated during 10 years; the 5-year budget impact was CHF 49.3/573.4 million under the lower/higher price. Estimates were sensitive to calibration targets and treatment eligibility; burden of disease/budget impact results also to uptake. Limitations included uncertainties about model assumptions and the size and characteristics of the population modelled.ConclusionsInclisiran may be cost-effective at a willingness to pay of CHF 30,000 if priced at CHF 500; a threshold upwards of CHF 250,000 will be required if priced at CHF 3000. Inclisiran could enable important reductions in cardiovascular burden particularly under broader eligibility with a budget impact range from moderate to high depending on price.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01152-8.

Effects of intensive blood pressure control on cardiovascular and cognitive outcomes in patients with atrial fibrillation: insights from the SPRINT trial.

Patients with atrial fibrillation (AF) have an increased risk of cardiovascular events and dementia, even if anticoagulated. Hypertension is highly prevalent in AF population; however, the optimal blood pressure (BP) target for AF patients remains unknown. We conducted subgroup analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) to examine whether AF modified the treatment effects of intensive BP control on cardiovascular and cognitive outcomes using Cox proportional hazards regression and likelihood ratio tests. Among 9361 randomized participants, 778 (8.3%) had baseline AF, and 695 (89.3%) completed at least one follow-up cognitive assessment. Intensive BP control reduced the similar relative risk of cardiovascular events irrespective of the presence of AF, with all interaction P-values > 0.05. Patients with AF experienced a greater absolute risk reduction in the composite primary cardiovascular outcome (12.3 vs. 5.6 events per 1000 person-years) with intensive treatment, compared with those without AF. However, intensive BP control increased the risk of probable dementia in patients with AF [hazard ratio (HR), 2.22; 95% confidence interval (CI), 1.03-4.80], while reducing the dementia risk in patients without AF (HR, 0.75; 95% CI, 0.60-0.95; P = 0.009 for interaction). There were no significant interactions between the presence of AF and intensive BP treatment for mild cognitive impairment. Patients with AF experienced greater absolute cardiovascular benefits with intensive BP treatment, but may need to be cautious of an increased risk of dementia. This post hoc analysis should be considered as hypothesis generating and merit further study. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Effect of Dapagliflozin on Cardiovascular Outcomes According to Baseline Kidney Function and Albuminuria Status in Patients With Type 2 Diabetes

Sodium-glucose cotransporter 2 inhibitors, such as dapagliflozin, promote renal glucose excretion and reduce cardiovascular (CV) deaths and hospitalizations for heart failure (HHF) among patients with type 2 diabetes. The relative CV efficacy and safety of dapagliflozin according to baseline kidney function and albuminuria status are unknown. To assess the CV efficacy and safety of dapagliflozin according to baseline estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR). This secondary analysis of the randomized clinical trial Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 compared dapagliflozin vs placebo in 17 160 patients with type 2 diabetes and a baseline creatinine clearance of 60 mL/min or higher. Patients were categorized according to prespecified subgroups of baseline eGFR (<60 vs ≥60 mL/min/1.73 m2), urinary albumin to creatinine ratio (UACR; <30 vs ≥30 mg/g), and of chronic kidney disease (CKD) markers using these subgroups (0, 1, or 2). The study was conducted from May 2013 to September 2018. Dapagliflozin vs placebo. The dual primary end points were major adverse cardiovascular events (myocardial infarction, stroke, and CV death) and the composite of CV death or HHF. At baseline, 1265 patients (7.4%) had an eGFR below 60 mL/min/1.73 m2, and 5199 patients (30.9%) had albuminuria. Among patients having data for both eGFR and UACR, 10 958 patients (65.1%) had an eGFR equal to or higher than 60 mL/min/1.73 m2 and an UACR below 30 mg/g (mean [SD] age, 63.7 [6.7] years; 40.1% women), 5336 patients (31.7%) had either an eGFR below 60 mL/min/1.73 m2 or albuminuria (mean [SD] age, 64.1 [7.1] years; 32.6% women), and 548 patients (3.3%) had both (mean [SD] age, 66.8 [6.9] years; 30.5% women). In the placebo group, patients with more CKD markers had higher event rates at 4 years as assessed using the Kaplan-Meier approach for the composite of CV death or HHF (3.9% for 0 markers, 8.3% for 1 marker, and 17.4% for 2 markers) and major adverse cardiovascular events (7.5% for 0 markers, 11.6% for 1 marker, and 18.9% for 2 markers). Estimates for relative risk reductions for the composite of CV death or HHF and for major adverse cardiovascular events were generally consistent across subgroups (both P > .24 for interaction), although greater absolute risk reductions were observed with more markers of CKD. The absolute risk difference for the composite of CV death or HHF was greater for patients with more markers of CKD (0 markers, -0.5%; 1 marker, -1.0%; and 2 markers, -8.3%; P = .02 for interaction). The numbers of amputations, cases of diabetic ketoacidosis, fractures, and major hypoglycemic events were balanced or numerically lower with dapagliflozin compared with placebo for patients with an eGFR below 60 mL/min/1.73 m2 and an UACR of 30 mg/g or higher. The effect of dapagliflozin on the relative risk for CV events was consistent across eGFR and UACR groups, with the greatest absolute benefit for the composite of CV death or HHF observed among patients with both reduced eGFR and albuminuria. ClinicalTrials.gov Identifier: NCT01730534.

Impact of gender on relative rates of cardiovascular events in patients with diabetes

AimTo investigate whether diabetes confers higher relative risks of cardiovascular events in women compared with men using contemporary data and also whether such gender-differences are dependent on age. MethodsAll patients discharged from French hospitals in 2013 with at least 5 years of follow-up and no history of major adverse cardiovascular events including heart failure (MACE-HF; heart failure, myocardial infarction, ischaemic stroke, cardiovascular death) were identified and categorized by diabetes status. Overall and age-stratified incidence rates, hazard ratios (HRs) and women-to-men ratios (WMRs) for MACE-HF leading to hospitalization were also calculated. Adjustments were then made for age and baseline characteristics according to cardiovascular risk factors and non-cardiovascular comorbidities. ResultsThe study included 2,953,816 subjects, among whom 349,928 (11.9%) had diabetes. Of those with diabetes, the absolute rate of MACE-HF was higher in men than in women (96 vs 66 per 1000 person-years); corresponding absolute rates in men and women without diabetes were 44 vs 27 per 1000 person-years. Comparing those with and without diabetes, women had a higher unadjusted HR of MACE-HF (2.45, 95% CI: 2.42–2.47) than men (2.15, 95% CI: 2.14–2.17), with an adjusted WMR of 1.13 (95% CI: 1.12–1.15). HRs of MACE-HF related to diabetes were highest in women aged around 45 years and in the youngest men and decreased with advancing age in both these groups. However, HRs were higher in women of all ages > 40 years. After adjustment, this effect was more apparent for myocardial infarction (adjusted WMR: 1.43, 95% CI: 1.38–1.48) than for either ischaemic stroke (adjusted WMR: 1.10, 95% CI: 1.07–1.14) or heart failure (adjusted WMR: 1.13, 95% CI: 1.11–1.14). ConclusionAlthough men have higher absolute risks of cardiovascular complications, the relative risks of cardiovascular complications associated with diabetes are higher in women than in men.

Real-world analyses of patients with elevated atherosclerotic cardiovascular disease risk from the Optum Research Database.

More than 56million Americans have hypertriglyceridemia, including over 12million statin-treated individuals. However, the contribution of elevated and high triglyceride levels to cardiovascular disease and death has not been extensively studied using real-world analyses. We review recent analyses of the Optum Research Database, which included patients aged ≥45years with diabetes and/or atherosclerotic cardiovascular disease and on statin therapy. Triglyceride levels ≥150and 200-499mg/dl were significantly associated with a 25.8and 34.9% increased relative risk of cardiovascular events, respectively, versus patients with triglyceride levels <150mg/dl. In addition, hypertriglyceridemia predicted peripheral arterial revascularization, new heart failure diagnosis and new-onset renal disease. Increased triglyceride levels were also significantly associated with increased healthcare resource utilization and costs. Interventions such as icosapent ethyl reduce triglycerides and associated cardiovascular disease risk.

Relationship of particular matter and temperature on the risk of adverse events in atrial fibrillation patients

Abstract Background Ambient particulate matter (PM), is a principal component of air pollutant and the main culprit of the adverse effects of air pollution on humans' health. In particular, PM with aerodynamic diameter &amp;lt;10 μm (PM10) has been shown to be associated with worse clinical outcomes. Similarly, cardiovascular risk increases during colder temperatures/seasons. Thus, both, air pollution and temperature fluctuations are examples confirming how the climate change is affecting our health. However, our knowledge about the impact of air pollution and temperature in anticoagulated atrial fibrillation (AF) patients is scarce. Purpose Herein, we investigated if PM10 and temperature are associated with an increased risk of adverse clinical outcomes in patients with AF taking vitamin K antagonists (VKAs). Methods We included AF patients who were stable on VKAs (INR 2.0–3.0) for 6 months in a tertiary hospital (Murcia, South-east Spain). During a median follow-up of 6.5 (IQR 4.3–7.9) years, ischemic strokes, major bleeds, adverse cardiovascular events, and mortality were recorded. From 2007–2016, data on average temperature and PM10 (PM with aerodynamic diameter &amp;lt;10 μm) were obtained and related to clinical outcomes. Results 1361 patients (48.7% male; median age 76, IQR 71–81 years) were included. High PM10 and low temperatures were associated with higher risk of major bleeding (adjusted Hazard Ratio, aHR 1.44, 95% CI 1.22–1.70 and aHR 1.03, 95% CI 1.01–1.05) and mortality (aHR 1.50, 95% CI 1.34–1.69 and aHR 1.04, 95% CI 1.02–1.06) (Table 1). PM10 was also significantly associated with ischemic stroke and temperature with cardiovascular events. The relative risk for cardiovascular events and mortality increased in months in the lower quartile (Q1) of temperature (&amp;lt;12.74°C) (RR 1.12, 95% CI 1.04–1.21 and RR 1.41, 95% CI 1.15–1.74; respectively). Comparing seasons, there were higher risks of cardiovascular events in spring, autumn, and winter than in summer, whereas the risk of mortality increased only in winter. Conclusions In AF patients taking VKAs highPM10 and low temperature were associated with an increased the risk of ischemic stroke and cardiovascular events, respectively. Both factors increased major bleeding and mortality risks, which were higher during colder months and seasons. Table 1. Univariate and Multivariate Cox Funding Acknowledgement Type of funding source: None

Chronic Obstructive Pulmonary Disease as a Predictor of Cardiovascular Risk: A Case-Control Study

Chronic obstructive pulmonary disease (COPD) is a complex multi-morbid disorder with significant cardiac mortality. Current cardiovascular risk prediction models do not include COPD. We investigated whether COPD modifies future cardiovascular risk to determine if it should be considered in risk prediction models.Case-control study using baseline data from two randomized controlled trials performed between 2012 and 2015. Of the 90 eligible subjects, 26 COPD patients with lung hyperinflation were propensity matched for 10-year global cardiovascular risk score (QRISK2) with 26 controls having normal lung function. Patients underwent cardiac magnetic resonance imaging, arterial stiffness and lung function measurements. Differences in pulse wave velocity (PWV), total arterial compliance (TAC) and aortic distensibility were main outcome measures.PWV (mean difference 1.0 m/s, 95% CI 0.02–1.92; p = 0.033) and TAC (mean difference –0.27 mL/m2/mmHg, 95% CI 0.39–0.15; p < 0.001) were adversely affected in COPD compared to the control group. The PWV difference equates to an age, sex and risk-factor adjusted increase in relative risk of cardiovascular events and mortality of 14% and 15%, respectively.There were no differences in aortic distensibility. In the whole cohort (n = 90) QRISK2 (β = 0.045, p = 0.005) was associated with PWV in multivariate analysis. The relationship between QRISK2 and PWV were modified by COPD, where the interaction term reached significance (p = 0.014). FEV1 (β = 0.055 (0.027), p = 0.041) and pulse (B = –0.006 (0.002), p = 0.003) were associated with TAC in multivariate analysis.Markers of cardiovascular outcomes are adversely affected in COPD patients with lung hyperinflation compared to controls matched for global cardiovascular risk. Cardiovascular risk algorithms may benefit from the addition of a COPD variable to improve risk prediction and guide management. HAPPY London ClinicalTrials.gov: NCT01911910 and HZC116601; ClinicalTrials.gov: NCT01691885

Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes

BackgroundE-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD. ObjectivesThis study sought to determine the early vascular impact of switching from TC to EC in chronic smokers. MethodsThe authors conducted a prospective, randomized control trial with a parallel nonrandomized preference cohort and blinded endpoint of smokers ≥18 years of age who had smoked ≥15 cigarettes/day for ≥2 years and were free from established cardiovascular disease. Participants were randomized to EC with nicotine or EC without nicotine for 1 month. Those unwilling to quit continued with TC in a parallel preference arm. A propensity score analysis was done to adjust for differences between the randomized and preference arms. Vascular function was assessed by FMD and pulse wave velocity. Compliance with EC was measured by carbon monoxide levels. ResultsWithin 1 month of switching from TC to EC, there was a significant improvement in endothelial function (linear trend β = 0.73%; 95% confidence interval [CI]: 0.41 to 1.05; p < 0.0001; TC vs. EC combined: 1.49%; 95% CI: 0.93 to 2.04; p < 0.0001) and vascular stiffness (−0.529 m/s; 95% CI: −0.946 to −0.112; p = 0.014). Females benefited from switching more than males did in every between-group comparison. Those who complied best with EC switch demonstrated the largest improvement. There was no difference in vascular effects between EC with and without nicotine within the study timeframe. ConclusionsTC smokers, particularly females, demonstrate significant improvement in vascular health within 1 month of switching from TC to EC. Switching from TC to EC may be considered a harms reduction measure. (Vascular Effects of Regular Cigarettes Versus Electronic Cigarette Use [VESUVIUS]; NCT02878421; ISRCTN59133298)

P1587Comparison of effects of lowering blood pressure in individuals with blood pressure &lt;140/90 mmHg and hypertension guideline recommendations: a systematic review and meta-analysis of randomised trials

Abstract Background Implementation of evidence-based medicine requires minimising delays between data generation and guideline creation. We examined the temporal relationship between accumulating evidence from randomized controlled trials (RCTs) of blood pressure (BP) lowering drug therapy among individuals with SBP&lt;140 mmHg, DBP&lt;90 mmHg, or both, and hypertension guideline recommendations over time. Methods A systematic review was conducted by searching MEDLINE for RCTs between January 1966 and February 2018. Included trials randomized patients to BP lowering drug(s) vs placebo/no treatment or to more vs less BP lowering with at least 1000 patient-years of follow-up per treatment group, and provided data relevant to BP lowering in patients with SBP&lt;140 mmHg, DBP&lt;90 mmHg, or both (hereafter &lt;140/90 mmHg). Included trials were classified according to major patient groups and whether all patients had baseline BP &lt;140/90 mmHg, or most control group patients had BP &lt;140/90 mmHg during follow-up, which was selected because this is the BP against which interventions were compared. Two reviewers independently extracted relevant data from included RCTs and hypertension guidelines. Cumulative meta-analyses of cardiovascular events were conducted and were compared to hypertension guideline recommendations. The primary outcome was major cardiovascular events. Results A total of 73 trials (n=300,805) were included, including 16 trials/subgroups with all participants baseline BP &lt;140/90mmHg. Benefits of BP lowering in individuals with usual BP &lt;140/90 mmHg began to emerge in the 1970s (Figure). Most evidence was from trials that included some or all patients with hypertension at baseline, but most patients had BP &lt;140/90 mmHg during follow-up due to regression to the mean and background treatment. Starting from 1992, 22 trials reported results by baseline hypertension status with no difference in cardiovascular event relative risk reduction among those with and without hypertension (relative risk 0.87 [95% CI 0.84–0.90] vs 0.86 [0.83–0.90], respectively. Until 2017, no major guidelines recommended treatment initiation or intensification for patients with baseline BP &lt;140/90 mmHg, apart from the periods during which some guidelines recommended treatment at lower thresholds for patients with diabetes and chronic kidney disease (Joint National Committee 1997 to 2014; European Society of Hypertension 2007 to 2009). Cumulative meta-analyses of trials Conclusions Evidence of benefits of BP lowering among individuals with usual BP &lt;140/90 mmHg have been demonstrated for decades. However, there has been a substantial delay between data generation and guideline recommendations. This delay was may be due to the inappropriate emphasis on baseline rather than usual BP levels, and relatively narrow evidence synthesis, which does not fully account for evidence generated across various major patient groups.

The prognostic value of various carotid ultrasound parameters in patients at high and very high cardiovascular risk

BackgroundAccording to the current guidelines the visualization of atherosclerotic plaques in the carotid arteries is the only option that carotid ultrasound provides for the assessment of cardiovascular risk (CVR). The direction devoted to the development and implementation of markers based on the quantification of atheroma, is promising. The aim of the study was to evaluate the prognostic value of various carotid ultrasound parameters in patients at high and very high CVR. MethodsPatients at high and very high CVR were included. All patients underwent carotid ultrasound. We evaluated carotid intima-media thickness (cIMT), carotid plaque, carotid plaque score (cPS) and carotid total plaque area (cTPA). The combined endpoint was cardiovascular death, non-fatal myocardial infarction or unstable angina, non-fatal stroke and coronary revascularization. ResultsThe study included 100 patients. The duration of the follow-up period was 24.4 (14.1–34.3) months. Endpoint events occurred in 34.0% patients. cIMT and cPS were not significantly associated with the risk of cardiovascular events. The presence of carotid plaque in accordance with Cox regression after adjusting for possible confounders was associated with an increase in the relative risk of cardiovascular events by 10.5 times (95% CI 1.27–86.5; p = 0.008). CTPA ≥69 mm2 according to adjusted analysis was associated with an increase in the risk of cardiovascular events by 5.86 times (95% CI 2.09–16.4; p = 0.001). ConclusionIn patients at high and very high CVR among carotid atherosclerosis markers only carotid plaque and cTPA had an independent predictive value regarding the development of adverse cardiovascular events.

Prognosis of cardiovascular events after implantation of a cardioverterdefibrillator in patients with chronic heart failure: the value of increasing concentration of endothelin-1 and soluble forms of ST2 protein in blood plasma

Aim.The purpose of this study was to examine the association of increasing concentrations of endothelin-1 and soluble forms of ST2 protein (sST2) in the blood plasma of patients with chronic heart failure (CHF) who underwent implantation of a cardioverter-defibrillator, with the development of cardiovascular events (death from cardiovascular diseases, decompensated CHF, acute coronary syndrome or acute ischemic stroke) to determine whether these biomarkers can be used as predictors of an unfavorable course of the disease.Material and methods. A 6-month cohort study included 40 patients with CHF who received an ICD 4-12 weeks before their inclusion in the study. At the beginning of the study the concentrations of endothelin-1 and sST2 in plasma by ELISA were analyzed, along with conventional diagnostic techniques typical of a specialized cardiology clinic.Results.Phenotype with a favorable course of the disease was identified in 21 patients (group 1), and with a unfavorable course was seen in 19 (group 2). The concentration of endothelin-1 and sST2 in the blood plasma of the 2nd group patients was higher than in patients of the 1st group. The link of cardiovascular events with high levels of soluble ST2 protein and endothelin-1 in blood plasma has been identified. Variation of the decision rule threshold on the ROC-curve has allowed sST2 concentration of 34.93 ng/ml to be determined as a cutoff point. Accuracy of two-class classification (determination of the posterior probability of cardiovascular events) after identifying such cut-off point was characterized by 93% sensitivity and 72% specificity (area under ROC-curve – 0.87). If the value of the plasma concentrations of sST2 more 34.93 ng/ml the relative risk of cardiovascular events was 4.4 (95% CI 1.7–11.1). The use of endothelin-1 surplus in plasma (cut-off point – 0.34 fmol/ml) in predicting cardiovascular events was lower: the sensitivity – 88%, specificity – 68% (area under ROC-curve – 0.74). When the concentration of endothelin-1 in blood plasma was more than 0.34 fmol/ml the relative risk of cardiovascular events was 2.7 (95% CI 1.2–6.3).Conclusion.The increase in the sST2 and endothelin-1 concentration in blood plasma may be considered as a predictor of cardiovascular events in CHF patients after implantation of cardioverter-defibrillator.

Dipeptidyl Peptidase-4 Inhibitors in Chronic Kidney Disease: A Systematic Review of Randomized Clinical Trials

Background: Chronic kidney disease (CKD) is common in patients with type 2 diabetes mellitus (T2DM) and limits therapeutic options. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of oral glucose-lowering agents and are known to be safe and effective in the general population. Methods: We searched Cochrane, EMBASE, and PubMed from the time of their inception until March 2015. We included randomized controlled trials analyzing the efficacy (change in hemoglobin A1C [HbA1C]) and safety of DPP-4 agents in individuals with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m²). We extracted study characteristics, participants' baseline characteristics, and safety outcomes from eligible studies. We performed a random effects meta-analysis to summarize the change in HbA1C and the relative risk of cardiovascular events in patients with T2DM and CKD. We also collected data on hypoglycemia, other serious adverse events, and mortality. Results: We reviewed 12 studies with 4,403 patients with CKD and 239 on dialysis, finding a mean weighted decline in HbA1C of -0.48 (95% CI -0.61 to -0.35) with DPP-4 inhibitor therapy compared to placebo. DPP-4 inhibitors did not result in any additional adverse events, hypoglycemic episodes, or increased mortality. Restricting to studies with low risk of bias did not alter these findings. Conclusions: DPP-4 inhibitors can lower HbA1C without increasing the risk of cardiovascular or other major adverse events in patients with CKD. Few studies reported critical adverse events such as heart failure and hypersensitivity. If compared with other oral antiglycemic drugs, the effect of DPP-4 inhibitors is limited; however, their low risk of hypoglycemia may favor their use in patients with CKD. Summary: This systematic review of DPP-4 inhibitors in CKD suggests that they reduce HbA1C by about 0.5%. Furthermore, there was not any increase in the risk for significant adverse events. More research is needed to determine the safety and efficacy of DPP-4 inhibitors in CKD.

Risk of Bias in Systematic Reviews of Non-Randomized Studies of Adverse Cardiovascular Effects of Thiazolidinediones and Cyclooxygenase-2 Inhibitors: Application of a New Cochrane Risk of Bias Tool.

BackgroundSystematic reviews of the effects of healthcare interventions frequently include non-randomized studies. These are subject to confounding and a range of other biases that are seldom considered in detail when synthesizing and interpreting the results. Our aims were to assess the reliability and usability of a new Cochrane risk of bias (RoB) tool for non-randomized studies of interventions and to determine whether restricting analysis to studies with low or moderate RoB made a material difference to the results of the reviews.Methods and FindingsWe selected two systematic reviews of population-based, controlled non-randomized studies of the relationship between the use of thiazolidinediones (TZDs) and cyclooxygenase-2 (COX-2) inhibitors and major cardiovascular events. Two epidemiologists applied the Cochrane RoB tool and made assessments across the seven specified domains of bias for each of 37 component studies. Inter-rater agreement was measured using the weighted Kappa statistic. We grouped studies according to overall RoB and performed statistical pooling for (a) all studies and (b) only studies with low or moderate RoB. Kappa scores across the seven bias domains ranged from 0.50 to 1.0. In the COX-2 inhibitor review, two studies had low overall RoB, 14 had moderate RoB, and five had serious RoB. In the TZD review, six studies had low RoB, four had moderate RoB, four had serious RoB, and two had critical RoB. The pooled odds ratios for myocardial infarction, heart failure, and death for rosiglitazone versus pioglitazone remained significantly elevated when analyses were confined to studies with low or moderate RoB. However, the estimate for myocardial infarction declined from 1.14 (95% CI 1.07–1.24) to 1.06 (95% CI 0.99–1.13) when analysis was confined to studies with low RoB. Estimates of pooled relative risks of cardiovascular events with COX-2 inhibitors compared with no nonsteroidal anti-inflammatory drug changed little when analyses were confined to studies with low or moderate RoB. The exception was a rise in the relative risk associated with ibuprofen from 1.07 (95% CI 0.97–1.18) to 1.14 (95% CI 1.03–1.26). The main limitation of our study was testing the instrument on a narrow range of pharmacoepidemiological studies; we cannot assume our findings extend to a broader range of interventions and settings.ConclusionsThe Cochrane RoB tool highlighted a wide range of risks of bias in studies included in two widely cited reviews and had the potential to change the conclusions of the reviews. Systematic reviews that incorporate non-randomized studies of medical interventions should include a detailed assessment of RoB for each included study.

The association of albuminuria and high-sensitivity C-reactive protein with the efficacy of HMG-coenzyme A reductase inhibitors for cardiovascular event prevention.

It is not clear which hypercholesterolemic patients benefit most from β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors with respect to the prevention of cardiovascular events. Early signs of atherosclerotic vascular damage may identify high-risk patients. We studied whether subjects with hypercholesterolemia will benefit more from starting statin treatment in the case of high albuminuria and/or high-sensitivity C-reactive protein (hsCRP). Included were subjects who had hypercholesterolemia at baseline, a negative cardiovascular disease history and who were not treated with statins. In total, 2011 subjects were analysed, of whom 695 started with a statin during a follow-up of 7.0 ± 1.7 years. Adjusted hazard ratios (HRs) for cardiovascular events were calculated in subjects who started versus those who did not start a statin stratified for albuminuria less than or ≥ 15 mg/day and/or hsCRP less than or ≥ 3 mg/L. The start of a statin was associated with a beneficial effect on cardiovascular risk in subjects with high albuminuria (HR 0.38 (0.23-0.60)), while the effect of starting a statin was non-significant in subjects with low albuminuria (HR 0.74 (0.44-1.24), P for interaction < 0.05). The effect of starting a statin was similar in subgroups with high and low hsCRP (P for interaction 0.34). When combining albuminuria and hsCRP subgroups, the start of statin treatment was associated with a lower risk of cardiovascular events dependent on albuminuria and not on the hsCRP level. The start of statin treatment is associated with a significantly lower absolute as well as relative risk of cardiovascular events in subjects with hypercholesterolemia and elevated albuminuria, whereas these drugs had less effect in subjects with normal albuminuria.

Association of Brachial-Ankle Pulse Wave Velocity With Cardiovascular Events in Atrial Fibrillation.

Atrial fibrillation (AF) and increased arterial stiffness share several risk factors and the 2 diseases often coexist. However, the prognostic value of increased arterial stiffness remains uncertain in the AF population. We evaluated whether brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness, can predict cardiovascular events, and determined that the baPWV is a more favorable prognostic marker compared with conventional clinical and echocardiographic markers in patients with AF. We enrolled 167 patients with persistent AF. Arterial stiffness was assessed using baPWV. Cardiovascular events were defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and hospitalization for heart failure. The relative risk of cardiovascular events was analyzed using Cox regression models. An improvement in model prediction was determined using the -2 log likelihood ratio statistic. During a median 26-month follow-up, 42 (24.9%) cardiovascular events were observed. The baPWV emerged as an independent predictor of cardiovascular events (adjusted hazard ratio: 1.152; 95% confidence interval: 1.054-1.259; P = 0.002) in the multivariate analysis. Furthermore, the addition of baPWV to a Cox model comprising standard clinical, biochemical, and echocardiographic parameters improved the prediction of adverse cardiovascular events (P < 0.001). In patients with AF, a high baPWV is associated with increased cardiovascular events and improve the prediction of adverse cardiovascular events. Hence, baPWV might be included when examining patients with AF for prediction of adverse cardiovascular outcomes.

An elevated lipoprotein(a) plasma level as a cardiovascular risk factor

IntroductionThe causal association of elevated lipoprotein(a) (Lp(a)) plasma levels with the increased cardiovascular risk is still controversial and presently there are no standard recommendations on managing of hyperLp(a)emia. Our retrospective analysis is aimed to explore the Lp(a) thresholds, the magnitude of various cardiovascular risk factors and their combinations. MethodsThe files of 544 outpatients from our Outpatient Department of Lipid Disorders were divided into quintiles with respect to Lp(a) levels and reviewed regarding age, gender, Body Mass Index, dyslipidemias, arterial hypertension, diabetes mellitus, smoking and incidence of vascular events in coronaries, carotids and lower extremities. Furthermore we built 15 small quantiles to identify the Lp(a) threshold more precisely. ResultsThe incidence odds ratio for cardiovascular events rose from 2.65 in the 2nd quintile with Lp(a) 483–821 mg/L to 6.36 in the 5th quintile (Lp(a) ≥ 1495 mg/L). The relative risk of cardiovascular events was 0.08 in subjects with a Lp(a) level under 232 mg/l and 3.6 at Lp(a) ≥ 315 mg/L. The magnitude of the combination of elevated Lp (a) with arterial hypertension factor exceeded that of gender, age and combination of arterial hypertension with smoking. ConclusionsA Lp(a) plasma level of higher than about 300 mg/L seems to be a threshold for occurring of cardiovascular events. The combination of raised Lp(a) with arterial hypertension was found to be the most important cardiovascular risk factor. Lp(a) levels under 232 mg/L appeared to be a marker for good prognosis.