Nonfatal Cardiovascular Outcomes Research Articles

Does stopping statin therapy used for primary prevention in older persons increase the risk of fatal or nonfatal cardiovascular outcomes?

Does stopping statin therapy used for primary prevention in older persons increase the risk of fatal or nonfatal cardiovascular outcomes?

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults

Introduction: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. Methods: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. Results: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8–1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24–3.56) and 0.45 per 100 person-years (95% CI: 0.26–0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62–4.84) and 0.75 per 100 person-years (95% CI: 0.39–1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56–3.16) and 0.21 per 100 person-years (95% CI: 0.067–0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8–1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). Conclusion: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Impact of atrial fibrillation on mortality and non-fatal cardiovascular outcomes in 145 293 patients admitted with COVID-19: a statewide population-linkage study

Abstract Background Atrial fibrillation (AF) is common in COVID-19 patients. The impact of AF on major-adverse-cardiovascular-events (MACE defined as all-cause mortality, myocardial infarction, ischaemic stroke, heart failure or revascularisation), recurrent admission with AF and venous thromboembolism in patients hospitalised with COVID-19 is not well-defined. Purpose This study aims to examine the impact of AF on long-term clinical outcomes including fatal and non-fatal cardiovascular outcomes in patients admitted with COVID-19. Methods Patients admitted with COVID-19 (1 January 2020 to 30 September 2021) were identified from the Admitted-Patient-Data-Collection database in New South Wales, the largest state of Australia, stratified by AF status (No-AF vs Prior-AF or New-AF during index COVID-19 admission) and followed up until 31 March 2022. A linkage look-back to year 2001 was performed to identify prior-AF history. Multivariable Cox regression was performed to assess the impact of AF status on MACE. To account for the competing risk of death and assess the impact of AF on non-fatal cardiovascular outcomes, Fine-Gray competing risk analysis was performed. Results The cohort comprised 145 293 COVID-19 patients (median age 67.4 years; 49.7% males): New-AF, n=5 140 (3.5%); Prior-AF, n=23 204 (16.0%) (Table 1). During a median follow-up of 9 months, Prior-AF and New-AF patients had significantly higher MACE rates (Prior-AF: 44.7% vs New-AF: 36.2% vs No-AF: 18.0%), including all-cause mortality (Prior-AF: 36.0% vs New-AF: 28.7% vs No-AF: 15.2%) compared to No-AF patients (both logrank P&amp;lt;0.001). After adjusting for age, gender, intensive-care-unit admission and Charlson comorbidity index, compared to No-AF status, New-AF and Prior-AF status were independently associated with MACE (adjusted hazard ratio[aHR]=1.17, 95% confidence interval [CI]=1.11-1.22; aHR=1.36, 95%CI=1.33-1.40 respectively; both P&amp;lt;0.001). Competing risk analyses showed that rehospitalisation rates for ischaemic stroke, heart failure and AF but not venous thromboembolism were significantly higher in COVID-19 patients with New-AF and Prior-AF (P&amp;lt;0.001) (Table 2). In a separate competing risk analysis incorporating patient’s CHA2DS2VASc status, New-AF patients had a higher rehospitalisation rate for ischaemic stroke, independent of CHA2DS2VASc group (CHA2DS2VASc=0 vs CHA2DS2VASc≥1: subdistribution HR [sHR]=3.57 and 1.61 respectively), whereas patients with Prior-AF had a higher rehospitalisation rate for ischaemic stroke only if CHA2DS2VASc≥1 (sHR=1.34) (all P&amp;lt;0.05). Conclusions COVID-19 patients with AF are at high risk of MACE and other adverse clinical outcomes. Such patients could be targeted for increased surveillance and additional post-discharge support. Efficacy of early anticoagulation for COVID-19 patients with new-AF to prevent stroke regardless of CHA2DS2VASc score requires further study.Table 1.Baseline characteristicsTable 2.Non-fatal CV outcomes

Adverse cardiovascular outcomes and sex-specific differences among older adults with cardiac ageing

Abstract Background Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. Methods Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. Results 956 participants [mean age 63±12.9 years, n=424 males (44%)] were categorized based on mitral peak early to late diastolic filling velocity (E/A) ratios: E/A &amp;lt;0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A &amp;gt;2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI 2.24-3.56), and 0.45 per 100 person-years (95% CI 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes were significantly different among E/A categories (log-rank p=0.0269). E/A&amp;lt;0.8 (HR 1.80, 95%CI 1.031, 3.14, p=0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI 2.62-4.84), and 0.75 per 100 person-years (95% CI 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI 1.56-3.16), and 0.21 per 100 person-years (95% CI 0.067-0.64) for all-cause death. For E/A&amp;lt;0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95%CI 1.18, 5.23, p=0.017). Conclusion Myocardial ageing was an independent predictor of cardiovascular outcomes. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.Myocardial Ageing in the Community

Impact of atrial fibrillation on mortality and non-fatal cardiovascular outcomes in 152 638 patients admitted with congestive cardiac failure: a statewide population-linkage study

Abstract Background Congestive cardiac failure (CCF) and atrial fibrillation (AF) frequently co-exist, cause and exacerbate each other. Prior studies on the impact of AF in CCF patients yielded mixed findings. Purpose This study aims to examine the impact of AF on long-term outcomes including MACE (major adverse cardiovascular events defined as all-cause mortality and major cardiovascular outcomes including myocardial infarction, ischaemic stroke, CCF or revascularization) and other non-fatal vascular or bleeding outcomes in patients admitted with CCF. Methods Hospitalised patients in New South Wales (NSW), the largest state of Australia, from 1 July 2003 to 31 March 2021 with a primary diagnosis of CCF were identified from the statewide Admitted-Patient-Data-Collection database, stratified by AF (Prior-AF or New-AF during index CCF admission) and No-AF status, with follow-up until 31 March 2022. A linkage look-back to year-2001 was performed to identify prior-AF history. In addition to MACE, non-fatal outcomes assessed included recurrent admission with AF, haemorrhagic stroke, peripheral arterial thromboembolism, pulmonary embolism, and bleeding. Multivariable Cox regression was performed to assess the impact of AF on MACE. To account for the competing risk of death and assess the impact of AF on non-fatal cardiovascular outcomes, Fine-Gray competing risk analysis was performed. Results The cohort comprised 152 638 admitted CCF patients (median age: 80.4 years; 51.4% males): New-AF, n=16 371 (10.7%); Prior-AF, n=56 546 (37.0%) (Table 1). During a median follow-up of 2.5 years, compared to No-AF CCF patients, those with New-AF or Prior-AF had significantly higher rates of MACE (New-AF: 81.7% vs Prior-AF: 86.3% vs No-AF: 78.5%) driven by all-cause mortality (New-AF: 71.6% vs Prior-AF: 76.5% vs No-AF: 66.2%) (both logrank P&amp;lt;0.001). However, after adjusting for differences in baseline characteristics and admission year-groups, New-AF and Prior-AF status had differential impact on MACE compared to No-AF patients (adjusted hazard ratio [aHR]=0.93, 95% confidence interval [CI]=0.91-0.94; aHR=1.14, 95%CI=1.13-1.16 respectively; both P&amp;lt;0.001). Results were similar for all-cause death (aHR=0.94 and aHR=1.16 respectively; both P&amp;lt;0.001). Competing risk analyses showed that rehospitalisation for ischaemic stroke, AF, haemorrhagic stroke, peripheral arterial thromboembolism and bleeding were significantly higher in CCF patients with New-AF and Prior-AF (P&amp;lt;0.001), after adjusting for age, sex, referral source, year-groups, intensive-care-unit admission and Charlson comorbidities index (Table 2). Conclusion This study shows that AF status has a differential impact on clinical outcomes in patients admitted with CCF. Drivers behind this difference in outcomes require further study and strategies should be developed to minimise the risk of adverse clinical outcomes in this vulnerable group of patients.Table 1.Baseline characteristicsTable 2.Non-fatal CV outcomes

Effects of blood pressure lowering according to baseline cardiovascular disease: systematic review and meta-analysis of randomized trials

Abstract Background Blood pressure (BP)-lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. There are no data on the effect of BP lowering in patients with a history of CV disease [i.e., coronary heart disease (CHD), stroke, or heart failure with preserved ejection fraction (HFpEF)]. Purpose To demonstrate the effect of BP-lowering treatment on CV events in patients with different types of baseline CV disease. Methods A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, search from 1966 to 11/2022) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on fatal or nonfatal cardiovascular outcomes and all-cause death. Trials or subgroups of trials were identified, including patients with a history of CV disease. We excluded heart failure studies with reduced ejection fraction, acute myocardial infarction, or acute stroke. Risk ratios (RR) were calculated with their 95% confidence interval (CI) under the random-effects model. Results We included 18 BP-lowering treatment trials with 52,359 CHD patients (mean follow-up, 4.2 years; achieved systolic/diastolic BP, 129.2/76.1 mmHg). Despite the fact that mortality outcomes, stroke, and recurrent CHD were not decreased as a result of BP-lowering therapy, the risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was reduced by 11% (95% CI, 3-18%) and the risk of recurrent heart failure hospitalization by 28% (95% CI, 18-38%). In addition, we examined 8 trials with 37,866 patients with a history of stroke (mean follow-up, 2.7 years; achieved systolic/diastolic BP, 136.5/79.8 mmHg), in which BP-lowering treatment reduced recurrent stroke by 18% (95% CI, 7-27%) and CV death by 12% (95% CI, 3-21%). Among 5 heart failure trials with 11,597 patients (mean follow-up, 3.4 years; achieved systolic/diastolic BP, 130.8/76.7 mmHg), the combined outcome of major CV events was decreased by 10% (95% CI, 4-16%), and recurrent heart failure hospitalization by 12% (95% CI, 4-19%). Conclusions Maximum CV protection is offered when systolic BP is reduced to levels &amp;lt; 130 mmHg in patients with CHD, to 130-140 mmHg levels in patients with a history of stroke, and to levels of approximately 130 mmHg in patients with heart failure. These findings support the recommendation for more aggressive BP lowering in patients with a history of CHD or optimally treated patients with HFpEF, and for less aggressive BP reduction in post-stroke patients.

Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome?

The Diuretic Comparison Project (DCP)1 was a real world study planned to evaluate in a pragmatic manner whether Chlorthalidone (CTD), as compared with Hydrochlorothiazide (HCTZ), would reduce the risk of major nonfatal cardiovascular disease outcomes in elderly hypertensive participants (≥65 years) who were receiving HCTZ (25 or 50 mg) at baseline. This study being a real world study lacks the robustness of a randomized controlled trial. The principle limitation being unequal exposure of the two diuretics, prolonged unknown duration of exposure to HCTZ vs a short exposure to CTD (Median 2.4 years). In the high risk population with history of MI/Stroke, CTD conferred a lower risk of primary outcome as compared to low risk population where no significant difference in outcome was seen in both diuretics. Other factors included, lack of established dose equivalency of the two diuretics and absence of use of 12.5 mg HCTZ in older hypertensives. How to cite this article: Pareek A, Messerli FH, Ram CVS. Chlorthalidone vs Hydrochlorothiazide for Hypertension-CV Events: Did the Design Influence the Outcome? J Assoc Physicians India 2023;71(10):93-93.

Study of the association between serum levels of kynurenine and cardiovascular outcomes and overall mortality in chronic kidney disease.

Kynurenine is a protein-bound uremic toxin. Its circulating levels are increased in chronic kidney disease (CKD). Experimental studies showed that it exerted deleterious cardiovascular effects. We sought to evaluate an association between serum kynurenine levels and adverse fatal or nonfatal cardiovascular events and all-cause mortality in CKD patients. The CKD-REIN study is a prospective cohort of people with CKD having an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m². Baseline frozen samples of total and free fractions of kynurenine and tryptophan were measured using a validated liquid chromatography tandem mass spectrometry technique. Cause-specific Cox models were used to estimate hazard ratios (HRs) for each outcome. Of the 2406 included patients (median age: 68 years; median eGFR: 25ml/min/1.73m2), 52% had a history of cardiovascular disease. A doubling of serum-free kynurenine levels was associated with an 18% increased hazard of cardiovascular events [466 events, HR (95%CI):1.18(1.02,1.33)], independently of eGFR, serum-free tryptophan level or other uremic toxins, cardioprotective drugs, and traditional cardiovascular risk factors. Serum-free kynurenine was significantly associated with non-atheromatous cardiovascular events [HR(95%CI):1.26(1.03,1.50)], but not with atheromatous cardiovascular events [HR(95%CI):1.15(0.89,1.50)]. The association of serum-free kynurenine with cardiovascular mortality was also independently significant [87 events; adjusted HR(95%CI):1.64(1.10,2.40)]. However, the association of serum-free kynurenine with all-cause mortality was no more significant after adjustment on serum-free tryptophan [311 events, HR(95%CI):1.12(0.90, 1.40)]. Our findings imply that serum-free kynurenine, independently of other cardiovascular risk factors (including eGFR), is associated with fatal or nonfatal cardiovascular outcomes, particularly non-atheromatous cardiovascular events; in patients with CKD. Strategies to reduce serum kynurenine levels should be evaluated in further studies.

BLOOD PRESSURE LOWERING TREATMENT AND BASELINE CARDIOVASCULAR RISK IN PRIMARY PREVENTION: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reduced cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk according to the SCORE-2 system. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 11/2022) for the effect of BP-lowering treatment against placebo, no treatment or less intense BP reduction on fatal or non-fatal CV outcomes. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We studied 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061. For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22-35%) in the category of very high-risk patients, and by 10% in the category of high-risk patients (p value for interaction = 0.020). Also, the relative risk reduction of the combined outcome was progressively greater the higher the baseline CV risk (p trend = 0.006). The risk reduction of CV death showed a significant trend from lower to higher baseline CV risk (p trend = 0.036). CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), and in the very high-risk group compared to the low-moderate risk group (p = 0.001). Conclusions: The greatest outcome benefit from BP lowering treatment in primary is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2.

Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals with diabetes mellitus.

The role of biomarkers in predicting cardiovascular outcomes in high-risk individuals is not well established. We aimed to investigate benefits of adding biomarkers to cardiovascular risk assessment in individuals with and without diabetes. We used individual-level data of 95 292 individuals of the European population harmonized in the Biomarker for Cardiovascular Risk Assessment across Europe consortium and investigated the prognostic ability of high-sensitivity cardiac troponin I (hs-cTnI), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). Cox-regression models were used to determine adjusted hazard ratios of diabetes and log-transformed biomarkers for fatal and non-fatal cardiovascular events. Models were compared using the likelihood ratio test. Stratification by specific biomarker cut-offs was performed for crude time-to-event analysis using Kaplan-Meier plots. Overall, 6090 (6.4%) individuals had diabetes at baseline, median follow-up was 9.9 years. Adjusting for classical risk factors and biomarkers, diabetes [HR 2.11 (95% CI 1.92, 2.32)], and all biomarkers (HR per interquartile range hs-cTnI 1.08 [95% CI 1.04, 1.12]; NT-proBNP 1.44 [95% CI 1.37, 1.53]; hs-CRP 1.27 [95% CI 1.21, 1.33]) were independently associated with cardiovascular events. Specific cut-offs for each biomarker identified a high-risk group of individuals with diabetes losing a median of 15.5 years of life compared to diabetics without elevated biomarkers. Addition of biomarkers to the Cox-model significantly improved the prediction of outcomes (likelihood ratio test for nested models P < 0.001), accompanied by an increase in the c-index (increase to 0.81). Biomarkers improve cardiovascular risk prediction in individuals with and without diabetes and facilitate the identification of individuals with diabetes at highest risk for cardiovascular events.

PS-C08-8: OUTCOMES FROM BLOOD PRESSURE REDUCTION IN PATIENTS WITH DIFFERENT BASELINE CARDIOVASCULAR RISK: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reducing cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk that was assessed according to SCORE-2. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We included 54 studies (i.e., 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients, and this reduction was significantly greater (P = 0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). Moreover, CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), as well as in the very high-risk group compared to the low-moderate risk group (p = 0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p = 0.045). Conclusions: The greatest outcome benefit from BP lowering in primary prevention is observed in patients at higher baseline cardiovascular risk as calculated by the SCORE-2.

Biomarker-based prediction of fatal and non-fatal cardiovascular outcomes in individuals of the general population with and without diabetes mellitus

Abstract Introduction Cardiovascular biomarkers may reflect different aspects of cardiovascular disease, including myocardial tissue damage (high-sensitive cardiac troponin [hs-cTn]), hemodynamic stress (N-terminal prohormone of brain natriuretic peptide [NT-proBNP)), or inflammation (high-sensitivity C-reactive protein [hs-CRP]). Purpose To determine the risk for fatal and non-fatal cardiovascular events in patients with diabetes mellitus (DM), a high-risk group for cardiovascular complications, after accounting for these biomarkers and to determine the risk associated with these biomarkers. Methods Harmonized data of population-based studies from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomaCaRE) and MOnica Risk, Genetics, Archiving and Monograph (MORGAM) consortia were used to calculate hazard ratios (HRs, 95% confidence intervals [CI] per standard deviation) for these biomarkers adjusted for diabetes, patient characteristics and biomarkers for their association with the primary endpoint of fatal and non-fatal cardiovascular events during a median follow-up of 9.6 years (maximum 28 years). Additionally, a years-of-life-lost analysis was conducted stratified by prevalent diabetes and specific biomarker cut-offs known to be associated with increased risk for events (hs-cTnI &amp;gt;5 ng/L, NTproBNP &amp;gt;125 ng/L, hs-CRP &amp;gt;5mg/L). Results We included 95,302 individuals, of whom 6,501 had DM (6.8%). Cox-regression analysis revealed DM to be independently associated with the primary endpoint (2.1 [95% CI 1.9, 2.3], p&amp;lt;0.001) despite adjustment for clinical characteristics and biomarkers. Also, all three biomarkers were independent predictors themselves: log-transformed NT-proBNP 1.3 [95% CI 1.3, 1.4] p&amp;lt;0.001; log-transformed hs-CRP 1.2 [95% CI 1.1, 1.2] p&amp;lt;0.001; third-root-transformed hs-cTnI 1.1 [95% CI 1.0, 1.1] p=0.0038). The sex-, age- and cohort-adjusted HR for the primary endpoint according to absolute biomarker concentrations derived by cox-regression models using cubic splines is provided for the three biomarkers in Figure 1. Upon dichotomization of biomarkers, individuals with diabetes and at least one elevated biomarker lost a median of 15.5 healthy years because of the primary endpoint (Kaplan-Meier plot in Figure 2, with age on the x-axis). Conclusion Our findings confirm that diabetes confers a residual cardiovascular risk beyond adjustment for clinical characteristics and cardiovascular biomarker. Furthermore, biomarkers may aid in the identification of patients at highest risk, which should be considered in future models of risk prediction. Funding Acknowledgement Type of funding sources: None.

Effect of blood pressure reduction on cardiovascular outcomes in patients with different baseline cardiovascular risk: systematic review and meta-analysis of randomized trials

Abstract Background/Introduction Blood pressure (BP) lowering is accompanied by a reduction on cardiovascular (CV) outcomes and death in hypertensive patients. There is no data on the effect of lowering BP in patients stratified according to their baseline CV risk as indicated by SCORE 2. Purpose The aim of this meta-analysis was to demonstrate the impact of BP-lowering treatment on the occurrence of CV events in these previously reported patients. Methods A systematic review in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) was conducted to identify randomized trials that study the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, baseline cardiovascular risk was estimated using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results The analysis was composed of 54 studies, of which 12 trials included patients with low-to-moderate CV risk, (n=21,192 patients), 13 trials with high CV risk patients (n=66,886) and 29 trials with very high CV risk patients (n=79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients. This reduction was significantly greater (p=0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). CV death showed a significant reduction in the high-risk group of patients compared to the low-moderate risk group (p=0.005), as well as in the very high-risk group compared to the low-moderate risk group (p=0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p=0.045). Conclusions With the present meta-analysis, we observed that the greatest benefit from BP lowering in primary prevention in the occurrence of CV events and mortality is observed in patients at higher baseline cardiovascular risk, as calculated by the SCORE-2. Funding Acknowledgement Type of funding sources: None.

Ordinal scoring of coronary artery calcification in low dose computed tomography is predictive factor of all-cause death and cardiovascular events

Abstract Background Lung cancer and cardiovascular disease (CVD) are leading worldwide mortality causes firmly related to smoking. Lung cancer screening (LCS) consisted in performing low-dose computed tomography (LDCT) offers an opportunity for simultaneous coronary artery calcification (CAC) assessment. Purpose The study aimed to determine the usefulness of the visual assessment of CAC in the prediction of all-cause death and non-fatal cardiovascular outcomes including myocardial infarction and stroke. Methods The study involved 6580 participants aged 50–79 years, current or former smokers with a cigarette smoking history of at least 30 pack-years, who were qualified for lung cancer screening program performed between April 2016 and May 2018. CAC was visually scored on ungated LDCT scans in the range of 0–12 based on the length of calcification involvement in four main coronary arteries. CAC severity was categorized into groups of 0, 1–3, 4–12. The primary outcome was all-cause mortality. The secondary outcome was major adverse cardiovascular events (composite of CVD death, nonfatal myocardiaI infarction, nonfatal stroke). The outcomes data were obtained by using the National Health Care Provider Registry of death and hospitalizations. The mean time of follow-up was 41.1 months (SD 8.3). Logistic regression analysis was used to determine the risk of mortality according to the CAC category adjusted for age, pack-years of cigarette smoking, and sex. Results The rate of all-cause death substantially increased in groups of higher CAC and it was consecutively 2.7% (89 of 3288 subjects) for a score of 0, 4.2% (66 of 1582 subjects) for a score of 1–3 and 8.3% (145 of 1742 subjects) for a score of 4–12. With the use of subjects with a CAC score of 0 as the reference group, adjusted for sex, age, and pack-years of smoking, a CAC score of at least 4 was a significant predictor of all-cause death (hazard ratio [HR], 1.89; 95% CI: 1.42; 2.52; P&amp;lt;0.05). Similar results were observed for the composite of CVD death, nonfatal myocardial infarction, nonfatal stroke with even greater significance. The rate of secondary outcames was 1.6% (51/3276) in a 0 score cohort, 3.0% (47/1570) in a 1–3 score cohort and 7.5% (130/1732) in a 4–12 score cohort. Both CAC score in the range 1–3 ([HR], 1.57; 95% CI: 1.05; 1.2.35; P&amp;lt;0.05), and 4–12 ([HR], 3.55; 95% CI: 2.50; 5.04; P&amp;lt;0.05) were a significant predictors of major adverse cardiovascular event incidence. Conclusions Visual assessment of CAC provides solid evidence of all-cause death and cardiovascular incidents independently of traditional coronary risk factors. Therefore evaluation of CAC in LDCT scans offers a unique opportunity for instituting CVD risk assessment in lung cancer screening program. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Centre for Research and Development of Poland.

Within-Visit Blood Pressure Variability and Cardiovascular Risk in ELSA-Brasil Study Participants.

ResumoFundamentoA variabilidade da pressão arterial (VPA) tem valor prognóstico para desfechos cardiovasculares fatais e não fatais.ObjetivosEste estudo teve como objetivo avaliar a associação entre a VPA em uma única visita e o risco cardiovascular em participantes do Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil).MétodosO presente estudo transversal foi conduzido com dados basais (2008-2010) de 14.357 participantes do ELSA-Brasil, sem história de doença cardiovascular. A VPA foi quantificada pelo coeficiente de variação de três medidas padronizadas da pressão arterial sistólica (PAS) realizadas com um oscilômetro. Medidas antropométricas e exames laboratoriais também foram realizados. O risco cardiovascular foi avaliado pelo estimador de risco de doença cardiovascular aterosclerótica (ASCVD), e se empregou a análise de regressão logística multivariada com nível de significância de 5%.ResultadosUm risco cardiovascular significativamente maior foi determinado por uma VPA elevada para ambos os sexos. Uma prevalência significativamente maior de alto risco foi observada mais em homens que em mulheres em todos os quartis, com a maior diferença observada no quarto quartil de variabilidade (48,3% vs. 17,1%). Comparações entre quartis por sexo revelaram um risco significativamente mais alto para homens no terceiro (OR=1,20; IC95%: 1,02 - 1,40) e no quarto quartis OR=1,46; IC95%: 1,25 -1,71), e para mulheres no quarto quartil (OR=1,27; IC95%: 1,03 - 1,57).ConclusãoAnálises de dados basais de participantes do ELSA-Brasil revelaram que a variabilidade da pressão arterial se associou com risco cardiovascular aumentado, especialmente nos homens.

BLOOD PRESSURE REDUCTION AND OUTCOMES IN PATIENTS WITH DIFFERENT BASELINE CARDIOVASCULAR RISK: SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED TRIALS

Objective: Blood pressure (BP) lowering is accompanied by reducing cardiovascular (CV) outcomes and death in hypertensive patients. No data are available for the effect of BP lowering in trials stratified according to baseline CV risk that was assessed according to SCORE-2. Design and method: A systematic review was conducted to identify randomized trials in electronic databases (Pubmed and CENTRAL, years: 1966 to 9/2021) for the effect of BP-lowering treatment against placebo or less aggressive BP reduction on 6 fatal or non-fatal CV outcomes and all-cause death. Selected studies reported outcomes in patients without a history of previous CV disease. In each study, we calculated baseline cardiovascular risk using SCORE-2. Risk ratios (RR) were calculated together with their 95% confidence interval (CI) under the random-effects model. Results: We included 54 studies (i.e., 12 trials with low-to-moderate CV risk, n = 21,192 patients; 13 trials with high risk, n = 66,886; and 29 trials with very high risk, n = 79,061). For a standard SBP/DBP reduction of 10/5 mmHg, the relative risk of the combined outcome of major CV events (i.e., myocardial infarction, stroke, and heart failure) was decreased by 27% (95% CI, 22–35%) in the category of very high-risk patients, and this reduction was significantly greater (P = 0.02) compared to high-risk trials (0.90 [95% CI, 0.77–1.04]). Moreover, CV death showed a significant reduction in the high-risk group compared to the low-moderate risk group (p = 0.005), as well as in the very high-risk group compared to the low-moderate risk group (p = 0.001). The same pattern was observed for all-cause death in the very high-risk group compared to the high-risk group (p = 0.045). Conclusions: The greatest outcome benefit from BP lowering in primary prevention is observed in patients at higher baseline cardiovascular risk as calculated by the SCORE-2.

Serum hepcidin levels and cardiovascular outcomes in patients on maintenance hemodialysis: a study from South India

Background Cardiovascular mortality is high in patients on maintenance hemodialysis. Different factors and plausible mechanisms have been explained for the increased risk. A recent concept of iron dysregulation and the related biomarker serum hepcidin was thought to be one of the novel markers of cardiovascular disease. We undertook this study to study the fatal and nonfatal cardiovascular events in dialysis population. Patients and methods All the patients who satisfied inclusion criteria were included in the study. All the patients have been on either twice-/thrice-weekly dialysis with polysulfone membrane of 1.3-m2 surface area. Serum hepcidin levels were estimated in blood samples using the appropriate techniques. All the patients were followed up for 18 months to assess the fatal and nonfatal cardiovascular outcomes. Results A total of 80 patients satisfied the criteria and were followed up. Mean serum hepcidin levels were 116.3 ± 32 ng/ml. On univariate analysis of factors influencing mortality, age, sex, and presence of comorbidities did not show significant association, but the levels of serum bicarbonate, albumin, creatinine, cholesterol, triglycerides, and the high-sensitivity C-reactive protein, hepcidin, showed a significant association with mortality. Serum hepcidin level of 120 ng/ml predicted mortality with a sensitivity of 100% and specificity of 85%. Conclusions Serum hepcidin is associated with all-cause mortality and cardiovascular mortality in patients on hemodialysis. Hepcidin levels may serve a good predictor of cardiovascular outcomes in patients on hemodialysis.

Monocyte chemoattractant protein-1 and hypertension: An overview

BackgroundThe association between hypertension and cardiovascular disease (CVD) has been increasingly studied through early inflammatory biomarkers. The monocyte chemoattractant protein-1 (MCP-1) is the main chemokine implicated in the inflammatory endothelial process, attracting monocytes and macrophages to the atherosclerotic plaque. MethodsWe reviewed the main observational studies that have analyzed serum MCP-1 in patients with hypertension regardless of CVD, relating them to target organ damage (TOD). ResultsAs endothelial dysfunction continues and TOD accumulates, MCP-1 has been perpetuated at higher levels. The relationship between this chemokine and the increase in comorbidities, such as chronic kidney disease, dyslipidaemia, diabetes, and coronary artery disease, became clearer from the observational studies. However, patients with such morbidities use medications with potential anti-inflammatory effects. ConclusionThere is no normal threshold of MCP-1 for the healthy population, nor a uniform curve pattern, due to a balance between genetic factors, age, gender, comorbidities, TOD, and anti-inflammatory effects of drugs. In fact, MCP-1 seems to have a promising role as a tool for further improvement in cardiovascular risk stratification, as prognostic studies have demonstrated an association with fatal and non-fatal cardiovascular outcomes, regardless of other clinical and laboratory predictors.

Effect of regional living conditions on middle-term cardiovascular outcomes: data from prospective stage of the ESSE-RF study

Aim. To assess regional living conditions with cardiovascular outcomes based on prospective stage of the Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) study.Material and methods. We used data from a 3- and 5-year prospective stage of the ESSE-RF study (2012-2013). For initial screening, 16210 people aged 25-64 were included. To characterize the regions of residence, 5 regional indices (RIs) were used. The following endpoints were considered: cardiovascular death, myocardial infarction, stroke, composite endpoint (cardiovascular death + myocardial infarction + stroke). To assess the correlations, generalized estimating equations with nested data structure (individuals in the regions) were used. The studied associations were adjusted for a wide range of potential effect modifiers.Results. There are multiple direct associations of RIs with the likelihood of all endpoints. The exception was the reverse association of Industrial RI with cardiovascular death. The most stable associations regarded Mixed RI, Industrial RI and Socio-geographical RI, with a high RI significance in endpoint development, compared with well-known individual cardiovascular risk factors. Separate associations were noted for Economic RI and Demographic RI.Conclusion. The results indicate a significant contribution of a number of regional living conditions to individual risk of fatal and non-fatal cardiovascular outcomes.

Effect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis.

BackgroundThe effects of omega-3 fatty acids (FAs), such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, on cardiovascular outcomes are uncertain. We aimed to determine the effectiveness of omega-3 FAs on fatal and non-fatal cardiovascular outcomes and examine the potential variability in EPA vs. EPA+DHA treatment effects.MethodsWe searched EMBASE, PubMed, ClinicalTrials.gov, and Cochrane library databases through June 7, 2021. We performed a meta-analysis of 38 randomized controlled trials of omega-3 FAs, stratified by EPA monotherapy and EPA+DHA therapy. We estimated random-effects rate ratios (RRs) with (95% confidence intervals) and rated the certainty of evidence using GRADE. The key outcomes of interest were cardiovascular mortality, non-fatal cardiovascular outcomes, bleeding, and atrial fibrillation (AF). The protocol was registered in PROSPERO (CRD42021227580).FindingsIn 149,051 participants, omega-3 FA was associated with reducing cardiovascular mortality (RR, 0.93 [0.88-0.98]; p = 0.01), non-fatal myocardial infarction (MI) (RR, 0.87 [0.81–0.93]; p = 0.0001), coronary heart disease events (CHD) (RR, 0.91 [0.87–0.96]; p = 0.0002), major adverse cardiovascular events (MACE) (RR, 0.95 [0.92–0.98]; p = 0.002), and revascularization (RR, 0.91 [0.87–0.95]; p = 0.0001). The meta-analysis showed higher RR reductions with EPA monotherapy (0.82 [0.68–0.99]) than with EPA + DHA (0.94 [0.89–0.99]) for cardiovascular mortality, non-fatal MI (EPA: 0.72 [0.62–0.84]; EPA+DHA: 0.92 [0.85–1.00]), CHD events (EPA: 0.73 [0.62–0.85]; EPA+DHA: 0.94 [0.89–0.99]), as well for MACE and revascularization. Omega-3 FA increased incident AF (RR, 1.26 [1.08–1.48]). EPA monotherapy vs. control was associated with a higher risk of total bleeding (RR: 1.49 [1.20–1.84]) and AF (RR, 1.35 [1.10–1.66]).InterpretationOmega-3 FAs reduced cardiovascular mortality and improved cardiovascular outcomes. The cardiovascular risk reduction was more prominent with EPA monotherapy than with EPA+DHA.FundingNone.