Major Cardiovascular Disease Research Articles

Cardiodermatology: the heart of the connection between the skin and cardiovascular disease.

The skin and cardiovascular systems are connected in unique and meaningful ways, and many diseases conventionally considered as being limited to one organ system are more closely related than previously believed. Major cardiovascular diseases and phenomena such as infective endocarditis, congestive heart failure, Kawasaki disease and thromboembolism are associated with specific skin findings, and advances in genetics, immunology and clinical epidemiology show that inflammatory dermatological diseases, such as psoriasis, have serious cardiovascular and cardiometabolic consequences. Additionally, commonly used cardiovascular therapies, such as antihypertensive medications, are associated with important cutaneous adverse effects, including photosensitivity, photocarcinogenesis and eczematous skin reactions. Moreover, systemic dermatological therapies, including retinoids, Janus kinase inhibitors and biologics, can alter the risk of cardiovascular and cardiometabolic diseases. In this Review on cardiodermatology, we provide interdisciplinary insights from dermatology and cardiology that will be of practical use to both cardiologists and generalists who manage cardiovascular and cardiometabolic diseases in patients with dermatological findings or histories. We discuss specific skin findings associated with cardiovascular diseases to aid in diagnosis; important cutaneous adverse effects of common cardiovascular therapies, for the purpose of treatment monitoring; and the effect of dermatological diseases and dermatological treatment on cardiovascular risk.

Abstract 4113411: Long Term Outcomes of Hypertension and Antihypertensive Drugs in Young Healthy Adults: A Nationwide Population-based Prospective Cohort Study in Korea

Background: Long term follow-up data on elevated blood pressure (BP) or antihypertensive drugs in young adults are scarce. The effect of hypertension (HTN) and antihypertensive medications on the cardiovascular disease incidence in young healthy adults (20~45 years) was analyzed using a large-scale population medical use database in Korea. Methods: In total, 4,590,597 young Korean adults without comorbidities who underwent regular health examination were included in this study. They were stratified into four groups according to their BP (optimal BP, normal BP, high normal BP, and HTN). The primary outcome was a composite of the incidence of myocardial infarction and ischemic and hemorrhagic stroke, obtained by tracking the medical use data of the first-ever ICD-10 codes. Subgroup analysis was conducted by categorizing the HTN group into two subgroups according to the prescription ratios of the antihypertensive drugs during the follow-up period. Results: The average age was 33.8 years and median follow-up duration was 15.9 years. HTN elevated the incidence risk of major cardiovascular disease by 2.16 times compared to that of the optimal BP group. Dyslipidemia and HTN were the most dominant risk factors for myocardial infarction and stroke, respectively. In the subgroup analysis, antihypertensive medications decreased the incidence of cardiovascular disease by 70% in all diseases. Conclusions: Cardiovascular risk factors, including HTN, contribute to major cardiovascular disease incidence in young adults. The antihypertensive medications decreased the major cardiovascular disease incidence estimates.

Abstract 4135352: Neighborhood-level Determinants and Disparities in Incident Type 2 Diabetes in a Population-Based Cohort, 2015–2020

Introduction: Living in an area with high Area Deprivation Index (ADI) is linked to worse cardiovascular disease (CVD) outcomes. However, the association of ADI with type 2 diabetes (T2D), a major CVD risk factor, is incompletely described. This knowledge may guide primary CVD prevention. Method: Rochester Epidemiology Project is a medical record linkage system of persons in southeast Minnesota and southwest Wisconsin. We identified 253,890 persons (aged 4–98 yrs on July 1, 2015) in 9 counties with >90% population coverage. ADI scores, from 2015 home addresses, were grouped into quartiles of low (Q1) to high (Q4) deprivation. We excluded persons with type 1 diabetes (T1D) or history of T2D and identified new T2D cases (2015-2020) using ICD codes, HbA1c and medications. We examined the association between ADI quartile and risk of incident T2D using Cox regression with persons right censored at death, T2D, T1D or last visit. Models were adjusted for age and gender, and reported adjusted hazard ratios (aHR [95% confidence interval]). Results: Age, gender, and race statistically differed across ADI quartiles (Table). Age × ADI interaction was significant ( P <.001). T2D incidence ranged from 6.3 (Q1) to 9.0 (Q4) per 1000 person-years ( P <.001). Women vs. men/non-binary persons (combined due to limited non-binary persons) had 30% lower risk of incident T2D (aHR 0.70 [0.67–0.72]). Risk of incident T2D was higher in persons from higher ADI areas. At median age of 48.6 yrs, the risk was 30% higher in Q2 (aHR 1.3 [1.22–1.38]), 38% higher in Q3 (aHR 1.38 [1.30–1.47]) and 53% higher in Q4 (aHR 1.53 [1.43–1.62]) vs. Q1. Higher ADI was associated with higher incident T2D in younger persons, with risk attenuation with increasing age (Figure). Conclusion: In this population cohort, persons, particularly of younger age, living in more deprived areas had a higher risk of incident T2D. ADI may help identify areas for targeted T2D screening, with implications for CVD screening and prevention.

Burden of Hyperlipidemia, Cardiovascular Mortality, and COVID-19: A Retrospective-Cohort Analysis of US Data.

Hyperlipidemia is a major cardiovascular disease (CVD) risk factor, but limited data on its mortality trends in CVD over time. We assessed annual hyperlipidemia-related CVD mortality trends in the United States, including the COVID-19 pandemic's impact. Mortality data were obtained from CDC repository between 1999 and 2020 among patients ≥15 years old, using ICD-10 codes hyperlipidemia (E78.0-E78.5) and CVD (I00-I99). Age-adjusted mortality rates (AAMR) per 1,000,000 population was standardized to the 2000 US population. Log-linear regression models were used to evaluate mortality shifts. Average annual percentage change (AAPC) from 1999-2019 was used to project 2020 AAMR, estimating pandemic-attributed excess deaths. From 1999 to 2020, 483,155 hyperlipidemia-related CVD deaths occurred. Despite a general CVD mortality decline, hyperlipidemia-related CVD AAMR rose from 36.33 in 1999 to 99.77 in 2019. Ischemic heart diseases (AAMR 49.39) were the leading cause while hypertension had the highest mortality increase (AAPC +10.23%). Mortality rates were higher in males (AAMR 104.87), non-Hispanic (AAMR 82.49), and rural populations (AAMR 89.98). Highest mortality was observed in Black populations (AAMR 84.35), those ≥75 years (AAMR 646.45), and Western US regions (AAMR 96.88). During the first pandemic year, deaths exceeded projections by 10.55%, with notable increases among ages 35-75 (14.23%), Hispanic (17.96%), Black (14.82%), and urban (11.68%) groups. Hyperlipidemia-related CVD mortality has risen over the past two decades, further heightened by the COVID-19 pandemic, with higher impact on males, Black Americans, the elderly, and rural residents. Further study is needed to understand contributing factors and mitigate disparities.

Cardiovascular morbidity and mortality among the population of the Arctic region of Russia

Relevance. Cardiovascular diseases (CVDs) are the most significant contributor to the global disease burden. CVDs are still the top leader in the nosology of death causes among the population of most countries and globally. Specific climate and geographical conditions in the Russian Arctic are responsible for high CVD risks; poor transport accessibility of some northern territories lead to restricted availability of sophisticated medical care to patients.The objective of the study is to characterize the epidemiology and dynamics of cardiovascular morbidity and mortality among the population of the Komi Republic (KR) throughout 2009 to 2022.Methods. For 2009 through 2022, an epidemiological analytical study (ecological study) was carried out regarding cardiovascular morbidity and mortality among the KR population (in the North-West Russia) using federal statistical observation formats; statistical data were recruited from the Federal State Statistics Service (Rosstat) and the Unified Interdepartmental Information Statistical System (EMISS). Statistical analysis included calculation of mortality-to-incidence ratio (MIR) and incidence-to-prevalence ratio.Results and discussion. For 2009 through 2022, the average annual CVD incidence rate among the KR population stood at (23.1 ± 0.5) ‰, with (277.3 ± 5.9) ‰ prevalence rate. A significant increase (from 21.0 to 29.3 %) in the proportion of coronary heart diseases (CHDs) in the nosology of primary morbidities was noted. The incidence-to-prevalence ratio showed multidirectional dynamics, with positive (growth rate in 2009–2022: +64.5 %) values for arterial hypertension (AH) vs. negative (growth rates: +31.8 and +23.7 %) values for CHDs and cerebrovascular diseases (CCVDs). The cardiovascular mortality rate in 2003–2017 decreased by 29.1 %showing an upward trend since 2018. MIR for CHDs, AH and CCVDs decreased by 33.4, 52.9 and 23.7 % respectively.Conclusion. CVDs remain the main cause of the disease burden in the KR population. The registered trends in morbidity and mortality rates due to major CVDs shows efficient performance of regional cardiology care.

Optimal Antihypertensive Systolic Blood Pressure: A Systematic Review and Meta-Analysis.

Systolic blood pressure (SBP) lowering reduces major cardiovascular disease (CVD) and all-cause mortality. However, the optimal target for SBP lowering remains controversial. We included trials with random allocation to an SBP <130 mm Hg treatment target and CVD as the primary outcome. Data were extracted from each study independently and in duplicate using a standardized protocol. Random-effects meta-analysis was used to obtain pooled hazard ratios (HRs) and 95% CIs for CVD and all-cause mortality comparing SBP <130 and ≥130 mm Hg treatment targets. A secondary analysis compared the same outcomes for randomization to an SBP target of <120 or <140 mm Hg. Seven trials, including 72 138 participants, met the eligibility criteria. Compared with an SBP target of ≥130 mm Hg, an SBP target of <130 mm Hg significantly reduced major CVD (HR, 0.78 [95% CI, 0.70-0.87]) and all-cause mortality (HR, 0.89 [95% CI, 0.79-0.99]). Compared with an SBP target of <140 mm Hg, an intensive SBP target of <120 mm Hg significantly reduced major CVD (HR, 0.82 [95% CI, 0.74-0.91]), but all-cause mortality was marginally insignificant (HR, 0.85 [95% CI, 0.71-1.01]). Adverse events were significantly more likely in the intensive SBP target groups, but the absolute risks were low. This study suggests targeting an SBP <130 mm Hg significantly reduces the risks of major CVD and all-cause mortality. The findings also support an SBP target of <120 mm Hg, based on a smaller number of trials. URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42023490693.

Long-Term Benefits and Safety of Statins in Patients with Kidney Failure: A Target Trial Emulation Study.

Patients with kidney failure are at elevated risk of cardiovascular diseases. Although statins were commonly used to mitigate cardiovascular disease risk among the population with high risk, the evidence for initiating statin therapy among patients with kidney failure remains inconclusive. This study aimed to investigate the long-term benefits and risks associated with statin therapy in patients with kidney failure. Using territory-wide public electronic health records in Hong Kong, 3,019 statin-eligible individuals with kidney failure and elevated LDL cholesterol ≥ 100 mg/dL from Jan 2008 to Dec 2015 were included for analysis. The framework of target trial emulation was adopted to investigate the risk of the major cardiovascular diseases (i.e., a composite of myocardial infarction, heart failure and stroke), all-cause mortality, as well as the major adverse events (i.e., myopathies and liver dysfunction) between statin initiators and statin non-initiators. The pooled logistic model was used to obtain the hazard ratio (HRs) for the outcomes of interest in both intention-to-treat (ITT) analysis and per-protocol (PP) analysis. Significant risk reduction associated with statin therapy (HR [95%CI]) was observed for major cardiovascular diseases (ITT: 0.78 [0.62, 0.98]; PP: 0.66 [0.50, 0.87]) and all-cause mortality (ITT: 0.80 [0.68, 0.95]; PP: 0.60 [0.48, 0.76]). The standardised 5-year and 10-year absolute risk reduction in per-protocol analysis was 7% (3%, 11%) and 11% (4%, 18%), respectively. No significant risks for the major adverse events were observed. Statin therapy was associated with lower risks of cardiovascular diseases and all-cause mortality in patients with kidney failure without a higher risk of major adverse events.

Long-term exposure to PM2.5 and mortality among Japanese community-dwelling adults

Abstract Background Long-term exposure to PM2.5 (particulate matter with a diameter of 2.5 μm or smaller) is a risk factor for mortality and cardiovascular disease including stroke. However, there was limited evidence for the association between PM2.5 exposure and stroke in Asia where the major cardiovascular disease is stroke. Additionally, the causal association between PM2.5 and respiratory disease is still unresolved. The aim of this study was to investigate the association between long-term exposure to PM2.5 and all-cause, cardiovascular, and respiratory disease mortality in a Japanese community-based prospective cohort. Methods This study included 46,974 participants (19,707 men; 27,267 women) from the second cohort of the Ibaraki Prefectural Health Study. The participants were followed up from baseline survey (in 2009) to 31 December 2019. We confirmed underlying causes by death certificates. Using the PM2.5 concentrations estimated by the inverse distance weighting methods based on ambient air monitoring data, administrative area level concentrations were assigned to each participant. The hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality using a Cox proportional hazard model were presented. Results We identified 2,789 all-cause deaths during the 470,178 person-years of follow-up. PM2.5 exposure had no significant association with all-cause and cause-specific mortality. The multivariable-adjusted HRs per 1 μg/m3 increase in the PM2.5 concentration were 0.94 (95% CI = 0.80-1.12) for coronary heart disease, 0.92 (95% CI = 0.81-1.04) for stroke and 1.09 (95% CI = 0.97-1.23) for non-malignant respiratory disease. Conclusions We observed little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5 whose concentrations ranged from 8.3 to 13.1 μg/m3. A somewhat increased trend for non-malignant respiratory disease mortality may not be negligible. Key messages • We found little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5. • Somewhat increased tendency for non-malignant respiratory disease mortality associated with PM2.5 exposure was observed.

Effect of alirocumab on coronary plaque stratified by atherothrombotic risks

Abstract Background Previous clinical studies have shown that high-risk subgroups including patients with major atherosclerotic cardiovascular disease (ASCVD) events and multiple atherothrombotic risk factors derive enhanced cardiovascular benefit from proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. To date, the effect of alirocumab on coronary plaque regression stratified by the number of atherothrombotic risk factors remains unknown. Purpose To investigate the utility of atherothrombotic risk stratification to identify patients with acute myocardial infarction (AMI) who have the greatest potential for benefit on plaque regression as assessed by intracoronary imaging from the addition of alirocumab to high-intensity statin therapy. Methods This was a substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Intravascular ultrasound (IVUS) was serially performed in non-infarct-related coronary arteries at baseline and after 52 weeks. Atherothrombotic risk factors defined in the 2018 ACC/AHA cholesterol guidelines include myocardial infarction, ischemic stroke, peripheral artery disease, age ≥65 years, familial hypercholesterolemia, coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, LDL-C ≥100 mg/dL despite maximum tolerated statin therapy, and history of heart failure. The key endpoint was the change in IVUS-derived percent atheroma volume (PAV) from baseline to 52 weeks. Results A total of 263 patients available for serial IVUS data were analyzed for the current study. The most prevalent atherothrombotic risk factors were current smoking (49%), hypertension (43%), and age ≥65 years (24%). Patients were divided into 3 groups according to the number of risk factors (0 risk factor: n=52, 1 risk factor: n=101, ≥2 risk factors: n=100). Patients with risk factors had greater PAV at baseline compared with those with 0 risk factor (39.0% vs. 42.6% vs. 42.8%, P=0.008). The addition of Alirocumab to high-intensity statin therapy demonstrated a significant reduction in PAV among patients with 0 risk factor (-2.66% vs. -1.02%, P=0.009) and those with 1 risk factor (-2.36% vs. -0.76%, P&amp;lt;0.001) (Figure 1). In contrast, patients with ≥2 risk factors had no significant PAV reduction by alirocumab (-1.72% vs. -1.12%, P=0.076, P for interaction=0.009). Conclusions Among AMI patients with no or 1 atherothrombotic risk factor, the addition of alirocumab to high-intensity statin therapy demonstrated greater coronary plaque regression. Patients with fewer risk factors thus appear to be more susceptible for atheroma regression.Change in PAV stratified by risk factors

Diabetes, chronic respiratory and cardiovascular diseases in Germany and Europe (EHIS-3 Survey)

Abstract Background We examined the prevalence of major NCD groups (diabetes, chronic respiratory diseases (CRD) and cardiovascular diseases (CVD)) as well as self-rated health (SRH) and health-related limitation in everyday activities among those with one of these NCD in Germany and Europe (average of 28 European countries (EU-28)). Methods Data was derived from the European Health Interview Survey (EHIS-3, 2019/20). Health indicators were: self-reported diabetes, CRD and CVD in the past 12 months; SRH (very good/good vs. fair, bad, very bad) and health-related limitations in usual everyday activities for at least 6 months (severe/moderate vs. no limitation). Educational level was operationalized via ISCED-11. Analyses are age-standardized to the European Standard Population 2013. Results Prevalence of major NCD in Germany were statistically significantly higher than in the EU-28: diabetes 8.1% vs. 7.1%, CRD 11.2% vs. 7.9% and CVD 6.6% vs. 5.4%. Highest prevalence was observed in the lowest educational group and lowest prevalence in the highest educational group for all of these NCD in Germany as well as in the EU-28. The proportion of a very good/good SRH among people having one of these NCD was higher in Germany compared to the EU-28: for people with diabetes 35.8% vs. 31.0%, with CRD 45.6% vs. 42.9% and with CVD 25.3% vs.19.1%. The proportion of health-related limitations among those having at least one of these NCD varied according to educational level in Germany as well as in the EU-28 with a higher prevalence among people with low educational level compared to high. Conclusions Even though prevalence of these NCD were higher in Germany, a higher proportion of very good/good SRH for people with one of these NCD was observed compared to the EU-28. Many factors such as severity of disease, disease management and care could explain this difference. Social inequalities were present not only in the prevalence of NCD but also in health-related limitations in Germany and Europe. Key messages • Prevalence of self-reported major NCD were higher in Germany while self-rated health among people having NCD was better than in Europe. • Health equity interventions in Germany and Europe are necessary.

Interactive effects of outdoor fine particulate matter and metabolic, behavioural, and psychosocial risk factors on cardiovascular disease: analysis of the PURE-China cohort study

Abstract Background Long-term PM2.5 exposure has been associated with an elevated risk of cardiovascular disease (CVD) and its associated risk factors.[1–4] There is a paucity of studies investigating the interactive effects of PM2.5 exposure and a comprehensive list of risk factors including metabolic, behavioural, and psychosocial risk factors on CVD risk.[5] Purpose This study aims to examine the interactive effects of PM2.5 exposure and metabolic, behavioural, and psychosocial risk factors on incident CVD. Methods The Prospective Urban Rural Epidemiology (PURE)-China cohort study is a population-based cohort study recruiting participants aged 35–70 years from 115 communities in 12 provinces of China between 2005 and 2009, and followed up until August 31, 2021.[6] Participants’ metabolic, behavioural, and psychosocial risk factor information was recorded. PM2.5 concentrations were extracted from a 1x1 km2 global model.[7,8] For this analysis, we included participants aged 35–70 years at baseline without a history of CVD, with at least one follow-up visit. The primary outcome was a composite of major cardiovascular events (CVD deaths, myocardial infarction, stroke, and heart failure). Additive interaction was measured by relative excess risk due to interaction (RERI), the proportion of disease attributable to interaction (AP), and the synergy index (SI).[9,10] To comply with the additive interaction method, we classified concentrations of PM2.5 into low and high levels by the median of 3-year average PM2.5 concentration (45.7 μg/m3, IQR: 33.7-74). Cox proportional hazard models were used to assess the associations of metabolic, behavioural, and psychosocial risk factors on incident CVD by PM2.5 concentrations. Results The PURE-China study recruited 47 931 participants, of which 39 329 are eligible for this analysis. During the median follow-up period of 11.9 years (IQR: 9.6-12.6), 1462 and 2155 major CVD events had occurred in the low and high PM2.5 group respectively. There was a synergistic interaction between PM2.5 and the systolic blood pressure (SBP) for CVD: RERI: 0.363, 95% CI: 0.196-0.531; AP: 0.098, 95% CI: 0.081-0.115; SI: 1.155, 95% CI: 1.132-1.177; high LDL cholesterol: RERI: 0.219, 0.003-0.436; AP: 0.135, 0.008-0.263; SI: 1.549, 0.947-2.533. A significant synergistic interaction was also identified between PM2.5 and household air pollution (RERI: 0.457, 0.292-0.622; AP: 0.277, 0.184-0.37; SI: 3.362, 1.409-8.019). Interactions between PM2.5 and low grip strength on CVD were significantly synergistic, but antagonistic between PM2.5 and low physical activity (RERI: -0.248, -0.485--0.012; AP: -0.174, -0.349-0.001; SI: 0.633, 0.412-0.971). Conclusion Addictive interaction was between PM2.5 and SBP, high LDL cholesterol, household air pollution, low grip strength and low physical activity on incident CVD, indicating the benefit of coordinated control strategies for metabolic, physical, and environmental risk factors for the prevention of CVD.

Comparison of cardiovascular disease risk assessment tools in primary prevention patients with raised lipoprotein(a)

Abstract Background Genetically inherited lipoprotein (a) (lp(a)) is an independent cardiac risk factor. The approach to cardiovascular disease (CVD) risk modification is, however, uncertain. Current CVD risk calculators do not take lp(a) into account and guidance suggests binary treatment decisions based on presentation of lp(a) without considering other risk factors. A new CVD risk assessment tool has been developed which includes lp(a) concentration, Lp(a) Clinical Guidance (lpaclinicalguidance.com). Purpose The aim was to compare the CVD risk estimations and management impact, over both 10 years and lifetime, using the HEART UK consensus statement, QRISK3, Lp(a) Score, Score-2, Score-2 OP, and LIFE-CVD assessment tools in 20 primary prevention patients with raised lp(a). Methods This was a retrospective analysis from an existing database, recruited through lipid and cardiology outpatient services, with raised lp(a), and no history of CVD. A random selection with a broad range of lp(a) concentrations were chosen. The 10-year risk threshold to treat was based on current NICE guidance at 10% and, in the absence of consensus, a lifetime risk threshold of 25%. Lp(a) was measured by a reference clinical laboratory using a Roche platform (Denka Seiken reagent, isoform insensitive). Results The subset (n=20) included patients with lp(a) ranging from 64 nmol/L to &amp;gt;720 nmol/L, aged 20 to 78 (12 females). Risk assessment tool age restrictions prohibited risk estimation in all patients (explaining the variation in denominator below). Figure 1 shows a comparison of 10-year risk assessment tools, figure 2 lifetime risk. HEART UK guidance would indicate 90% of patients (18/20) were eligible to commence lipid lowering therapy, however, all patients would have treatment indicated based on Lp(a) Score (16/16). Using Score-2, no patients would have treatment indicated (0/6). Only 25% of patients (1/4) would have treatment indicated using Score-2 OP despite a minimum age criterion that alone introduces a major CVD risk factor. Of the remaining risk estimation tools: LIFE-CVD, QRISK3 lifetime risk, and QRISK3 10-year risk indicated 85% (11/13), 50% (8/16), and 38% (6/16) of patients, respectively, would have treatment indicated. Conclusions In primary prevention patients with raised lp(a), CVD risk estimation and decision-making is impaired by discrepancies in risk assessment tools. There may be underestimation in CVD risk, and subsequently under-treatment, with principal use of QRISK3 10-year risk to guide lipid lowering therapy. Lifetime CVD risk may be underestimated by QRISK and LIFE-CVD proportionally to the degree of elevation of lp(a). Risk assessment is imperfect; population data can only provide limited information when applied to an individual and the wide discrepancy found here calls into question the validity of risk estimation formulae in this population, or alternatively provides a range of tools for clinicians to select to suit the question asked.

Influence of orthostatic blood pressure changes on the effects of intensive blood pressure control in patients with type 2 diabetes

Abstract Background Intensive blood pressure (BP) control has been proven to reduce the risks of major cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM) (1). Excessive orthostatic BP changes should be fully addressed, given its high prevalence and associations with adverse events among T2DM patients (2-5). However, the benefits of intensive BP control among T2DM patients with significant orthostatic BP changes have been equivocal. Purpose To examine whether orthostatic BP changes modify the efficacy of intensive BP control on CVD outcomes in patients with T2DM. Methods The Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial (ACCORD BP) is a 2×2 factorial designed trial that aimed to evaluate the effects of intensive glycemia and BP control on major CVD events among T2DM patients (6). We enrolled participants with at least one record of orthostatic BP values for analysis. The composite CVD outcome in this study comprised cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalized congestive heart failure. Associations between orthostatic BP changes and the composite CVD outcome and all-cause death, respectively, were presented by restricted cubic spline curves based on multivariable Cox models. We examined if the effects of intensive BP control varied across the orthostatic BP change for the composite CVD outcome and all-cause death. Results Among 4330 participants, 877 (20.3%) experienced episodes of orthostatic hypotension (OH) at baseline or during follow-up. There was no significant difference in the proportions of OH participants between the intensive and standard BP arms. U-shaped associations were observed between orthostatic systolic BP changes and the composite CVD outcome, as well as all-cause mortality (Figure 1). In the standard glycemia arm, intensive BP control was significantly associated with a lower risk of composite CVD outcome (HR 0.76, 95%CI 0.59-0.97). There was a beneficial association of intensive BP control with all-cause mortality without statistical significance (HR 0.85, 95%CI 0.56-1.30). The favorable effect of intensive BP control was not influenced by orthostatic BP changes (P for interaction 0.51 for the composite CVD outcome and 0.97 for all-cause mortality) (Figure 2). Beneficial effects of intensive BP control were not observed for participants in the intensive glycemia arm on the composite CVD outcome (HR 0.99, 95%CI 0.76-1.28) and all-cause mortality (HR 1.19, 0.79-1.80). Conclusion Orthostatic BP changes should not be a barrier to intensive BP control for T2DM patients treated with guideline-recommended standard glycemia control.

Blood pressure lowering efficacy of antihypertensive drugs and their combinations: a systematic review and meta-analysis of 500 randomised, double-blind placebo-controlled trials

Abstract Background Each 1 mmHg reduction in systolic blood pressure (SBP) reduces the risk of major cardiovascular disease events by about 2%. However, there are currently no tools to provide randomised trial-derived estimates of blood pressure (BP)-lowering efficacy of different antihypertensive regimens despite the vast number of possible drug-dose permutations. There has also been no attempt to classify efficacy of treatment regimens into low, moderate, and high intensity. Purpose We aimed to quantify the BP-lowering efficacy of the five major classes of antihypertensive drugs and their combinations. Methods We conducted a systematic review and meta-analysis of randomised double-blind placebo-controlled trials. CENTRAL, MEDLINE and Epistimonikos were searched from inception until December 2022 to identify trials, that compared angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, calcium channel blockers, and diuretics versus placebo, for 4-26 weeks. Primary outcomes were reduction in SBP and diastolic blood pressure (DBP). Doses were classified into standard dose based on the World Health Organisation Defined Daily Dose. BP-lowering efficacy was estimated for each drug and dose using fixed-effects meta-analyses and meta-regressions, standardised to baseline SBP 154 mmHg. Treatment regimens were categorised into low, moderate, and high intensity according to estimated SBP-lowering efficacy of &amp;lt;10, 10-19 and ≥20 mmHg, respectively. Results A total of 500 trials (106,358 participants, 44% female) were included, which included 66 single antihypertensive drugs (monotherapy) and 89 two drug (dual) combinations. The mean baseline BP was 154/100 mmHg and mean follow-up was 8.6 weeks. Monotherapy at one standard dose reduced SBP by 8.5 (95% CI, 8.2-8.9) mmHg, with an additional 1.2 (1.0-1.5) mmHg reduction for each 10 mmHg higher pre-treatment SBP, and an additional 1.5 (1.2-1.8) mmHg reduction with each doubling in dose. There was significant heterogeneity between monotherapies, and 72% were classified as low intensity efficacy. Dual combinations at one standard doses of both the drugs reduced SBP by 15.2 (13.4-17.1) mmHg, and an additional 2.6 (1.4-3.8) mmHg reduction with doubling the doses of both the drugs. There was considerable heterogeneity between dual combinations and 59% were classified as moderate, and 11% as high intensity efficacy. The BP lowering efficacy of adding additional drug classes was confirmed to be additive after accounting for pre-treatment SBP. Triple combinations were classified as high intensity efficacy based on meta-regression analyses. Conclusions There is significant variability in the efficacy of different BP-lowering regimens. The present analyses, available in an online tool, can estimate the BP lowering efficacy for any combination of drug(s) and dose(s), and can classify treatment regimens into low, moderate or high intensity.

Effects of cardiac resynchronization therapy and physiologicaL pacing on left atrioventricular coupling index: the REPHYL-LACI study

Abstract Introduction Cardiac dyssynchrony and right ventricular pacing are associated with left atrial (LA) remodeling and atrioventricular uncoupling. Cardiac resynchronization therapy -CRT and conduction system pacing –CSP are important therapeutic options. Left atrioventricular coupling index (LACI) is a novel imaging parameter useful to describe the relationship between LA and left ventricle (LV). It could be measured as the ratio between LA end-diastolic volume (EDV) and the LV EDV or, alternatively, as the LA volume indexed for body surface area (LAVi) divided for a’ measured by tissue Doppler imaging (TDI) at medial mitral annulus level. Higher values indicate greater impairment of atrioventricular coupling. However, LACI has not been investigated in patients treated with CRT or CSP, and there is no comparison data about the two different measurement methodologies with echocardiography. Purpose To study the effects of CRT/CSP on LACI. Methods We retrospectively collected clinical, ECG and echocardiographic data of patients treated with standard CRT or CSP. Changes between baseline and follow-up (i.e. before and after CRT/CSP) were tested for significance. Baseline features were compared with these of a control group of patients without established major cardiovascular diseases. Results We enrolled fifty-six patients (median age at first echo 78[72.5-82]years; males 70%) and 56 controls (median age 77[72.5-83]years, p=0.974; males 57%, p= 0.170). Main clinical/instrumental data are shown in Table 1 and 2. In patients treated with CRT/CSP baseline LACIv (LAVid/LV EDV) was significantly lower than in controls (31[21-44]%vs34[29-48]%, p=0.040), despite higher LAVi and LV volumes in the first group (p&amp;lt;0.0001 for both). Conversely, LACId (LAVi/TDI-a’) was significantly higher in the CRT/CSP (4.48[2.81-8.28]vs2.89[2.36-3.67]mlxsecond/cm-1, p&amp;lt;0.0001). After a median follow-up of 515[282-1326]days, patients treated with CRT/CSP showed a significant increase of both LACIv (40[29-50]%, p=0.004) and LACId (4.95[3.77-9.89], p&amp;lt;0.0001). This worsening of atrioventricular coupling was accompanied by a trending LA dilatation with significant reduction of its reservoir function compared to baseline (expansion index 0.58[0.38-1.30]vs0.43[0.29-0.58], p=0.0002), despite a tendency toward stability or improvement of LV size and systolic/diastolic parameters. Conclusions In patients treated with CRT/CSP there is a worsening of LACI over time. We can speculate that the detrimental effects of artificial pacing might not be adequately counterbalanced by CRT/CSP, or that LV and LA pathology follow alternative trajectories with different responses to treatments. Moreover, the measurement of LACId should be probably avoided in patients with conduction disorders or paced. Further larger case-control studies are needed to clarify the usefulness of LACI as a valid parameter to assess atrioventricular coupling and its changes over time in patients treated with CRT/CSP.

Sex differences in secondary prevention and outcomes post-myocardial infarction in Scotland

Abstract Background Sex differences in outcomes after myocardial infarction (MI) are of increasing interest. Differential receipt of evidence-based treatments may contribute to such disparities. Purpose In this study, we investigate sex differences in the burden of risk factors, in-hospital and long-term treatment and outcomes in contemporary practice in Scotland, by analysing a nationwide sample of consecutive MI admissions. Methods All MI admissions centrally recorded between 2010-2016 by Public Health Scotland were included and followed up until the end of 2021. Poisson regressions analysed in-hospital outcomes (percutaneous coronary intervention (PCI), mortality and post-discharge secondary prevention medication). Models were adjusted for age, co-morbidities and ST-elevation on the electrocardiogram. Royston-Parmar models analysed long-term outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events (MACE)) and were sequentially adjusted for confounders (age, comorbidities, secondary prevention medications). A 2:1 age and sex-matched general population were included as controls. Results Of a total 47,063 MI patients, 15,776 (33.5%) were women. They were matched with 81,641 controls free of major cardiovascular disease. Median (interquartile range) age was 64 (56-72) years for men and 69 (60-75) years for women. Obesity, hypertension and renal disease were the risk factors more prevalent amongst women, while men had higher rates of previous MI, peripheral vascular disease and atrial fibrillation. Compared to men, women were less likely to undergo PCI (risk ratio (95% confidence interval) – 0.87 (0.86-0.89)) or receive secondary prevention (0.94 (0.93-0.95)), but had similar in-hospital mortality (1.06 (0.99-1.13)), after multi-variable adjustment. Over a median follow-up of 8.4 (6.8-10.2) years, women had higher raw rates of adverse outcomes. However, after full confounder adjustment, this translated into lower risk for women of all cause-mortality 0.92 (0.89-0.95), cardiovascular mortality 0.82 (0.78-0.87) and MACE 0.92 (0.88-0.95) (Figure 1). The female survival advantage was attenuated post-MI in comparison to controls free of significant cardiovascular disease (Figure 2). Conclusions Women and men have different MI risk factor profiles. Women had overall worse crude outcome rates after MI, driven by age and comorbidities. This may have been driven further by undertreatment after MI, including PCI and secondary prevention. Urgent identification of drivers for such disparities in care is warranted in order to improve outcomes and ensure health equity.

Prospective associations of genetic susceptibility to high blood pressure and muscle strength with incident cardiovascular disease outcomes.

This study explored the prospective associations of genetic susceptibility to high blood pressure (BP) and muscle strength with cardiovascular disease (CVD) mortality, incident coronary heart disease (CHD) and incident stroke. This study included 349 085 white British individuals from the UK Biobank study. Genetic risk of high BP was estimated using a weighted polygenic risk score that incorporated 136 and 135 nonoverlapping single-nucleotide polymorphisms for systolic BP and diastolic BP, respectively. Muscle strength was assessed using a hand dynamometer and expressed relative to fat-free mass. Sex- and age-specific tertiles were used to classify muscle strength into three categories. Cox regressions with age as the underlying timescale were fit for CVD mortality (n = 8275), incident CHD (n = 14 503), and stroke (n = 7518). Compared with the lowest genetic risk of high BP (bottom 20%), the highest (top 20%) had greater hazards of each outcome. Low muscle strength was associated with higher hazards of CVD mortality [hazard ratio (HR): 1.51, 95% confidence interval (CI): 1.43-1.59], incident CHD (HR: 1.16, 95% CI: 1.11-1.21), and stroke (HR: 1.20, 95% CI: 1.14-1.27), independently of confounders and genetic predisposition to high BP, compared with high muscle strength. Joint analyses revealed that the estimated 10-year absolute risks of each outcome were lower for high muscle strength combined with high genetic risk, compared with low muscle strength combined with low or medium genetic risk. Individuals who are genetically predisposed to high BP but have high muscle strength could have lower risk of major CVD events, compared with those who have low or medium genetic risk but low muscle strength.

Interaction between non-alcoholic fatty liver disease and obesity on the risk of developing cardiovascular diseases

BackgroundsThis investigation seeks to explore the correlation between nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), and to to provide evidence for the prevention and treatment of CVDs.MethodsThis study utilized data from the Jinchang cohort platform, including 19,399 participants without pre-existing major CVDs. Based on the general population and gender stratification, Cox models were used to analyze the risk of NAFLD for CVDs. The combined effect of NAFLD and different obesity indicators on CVDs was analyzed by additive and multiplicative interaction models and subgroups.ResultsThere were 3129 NAFLD patients out of 19399 subjects, and 723 (23.11%) of them had the CVD. After adjusting for multiple confounding factors, the Cox model revealed a 1.17-fold increase in the risk of CVDs among patients with NAFLD compared to those without NAFLD. Moreover, there was no notable disparity in CVDs risk among most NAFLD patients at the same level of obesity. The results indicated no additive interaction between NAFLD and obesity concerning CVDs risk, but rather a positive multiplicative interaction. Using the normal population as a reference, it was found that people with both obesity and NAFLD significantly increased the risk of developing CVDs, with HRs and 95% CIs of 1.790 (1.508, 2.126), 1.356 (1.213, 1.517), and 1.807 (1.503, 2.174), respectively, for BMI, WC, and the combination of BMI and WC.ConclusionsNAFLD and obesity are independent risk factors for CVDs. The synergy of obesity and NAFLD implies that NAFLD patients should control weight gain. Larger BMI and WC values may increase the CVDs risk for NAFLD patients, especially women.

Device-measured stationary behaviour and cardiovascular and orthostatic circulatory disease incidence.

Previous studies have indicated that standing may be beneficially associated with surrogate metabolic markers, whereas more time spent sitting has an adverse association. Studies assessing the dose-response associations of standing, sitting and composite stationary behaviour time with cardiovascular disease (CVD) and orthostatic circulatory disease are scarce and show an unclear picture. To examine associations of daily sitting, standing and stationary time with CVD and orthostatic circulatory disease incidence. We used accelerometer data from 83 013 adults (mean age ± standard deviation = 61.3 ± 7.8; female = 55.6%) from the UK Biobank to assess daily time spent sitting and standing. Major CVD was defined as coronary heart disease, heart failure and stroke. Orthostatic circulatory disease was defined as orthostatic hypotension, varicose vein, chronic venous insufficiency and venous ulcers. To estimate the dose-response hazard ratios (HR) we used Cox proportional hazards regression models and restricted cubic splines. The Fine-Gray subdistribution method was used to account for competing risks. During 6.9 (±0.9) years of follow-up, 6829 CVD and 2042 orthostatic circulatory disease events occurred. When stationary time exceeded 12 h/day, orthostatic circulatory disease risk was higher by an average HR (95% confidence interval) of 0.22 (0.16, 0.29) per hour. Every additional hour above 10 h/day of sitting was associated with a 0.26 (0.18, 0.36) higher risk. Standing more than 2 h/day was associated with an 0.11 (0.05, 0.18) higher risk for every additional 30 min/day. For major CVD, when stationary time exceeded 12 h/day, risk was higher by an average of 0.13 (0.10, 0.16) per hour. Sitting time was associated with a 0.15 (0.11, 0.19) higher risk per extra hour. Time spent standing was not associated with major CVD risk. Time spent standing was not associated with CVD risk but was associated with higher orthostatic circulatory disease risk. Time spent sitting above 10 h/day was associated with both higher orthostatic circulatory disease and major CVD risk. The deleterious associations of overall stationary time were primarily driven by sitting. Collectively, our findings indicate increasing standing time as a prescription may not lower major CVD risk and may lead to higher orthostatic circulatory disease risk.

The Influence of Physical Activity and Diet Mobile Apps on Cardiovascular Disease Risk Factors: Meta-Review.

The literature on whether physical activity (PA) and PA and diet (PA+Diet) mobile apps improve cardiovascular disease (CVD) risk factors is promising. The aim of this meta-review is to provide an evidence synthesis of systematic reviews and meta-analyses examining the influence of PA and PA+Diet apps on the major CVD risk factors. We systematically searched 5 databases until January 12, 2022. Included systematic reviews and meta-analyses (1) reported the CVD risk factor outcomes of BMI, waist circumference, body weight, blood pressure (BP), hemoglobin A1c (HbA1c), fasting blood glucose, blood lipids, or PA; (2) enrolled healthy participants ≥18 years who may or may not have the metabolic syndrome, diabetes mellitus, or preexisting CVD risk factors; (3) reviewed PA or PA+Diet app interventions integrating behavioral change techniques (BCT) to deliver their information; and (4) had a nonapp control. In total, 17 reviews (9 systematic reviews and 8 meta-analyses) published between 2012 and 2021 qualified. Participants were middle-aged, mostly women ranging in number from 10 to 62,219. Interventions lasted from 1 to 24 months, with the most common behavioral strategies being personalized feedback (n=8), self-monitoring (n=7), and goal setting (n=5). Of the PA app systematic reviews (N=4), the following CVD risk factors improved: body weight and BMI (n=2, 50%), BP (n=1, 25%), HbA1c (n=1, 25%), and blood lipids (n=1, 25%) decreased, while PA (n=4, 100%) increased. Of the PA+Diet app systematic reviews (N=5), the following CVD risk factors improved: body weight and BMI (n=3, 60%), BP (n=1, 20%), and HbA1c (n=3, 60%) decreased, while PA (n=3, 60%) increased. Of the PA app meta-analyses (N=1), the following CVD risk factors improved: body weight decreased (-0.73 kg, 95% CI -1.45 to -0.01; P=.05) and PA increased by 25 minutes/week (95% CI 0.58-1.68; P<.001), while BMI (-0.09 kg/m2, 95% CI -0.29 to 0.10; P=.35) and waist circumference (-1.92 cm, 95% CI -3.94 to 0.09; P=.06) tended to decrease. Of the PA+Diet app meta-analyses (n=4), the following CVD risk factors improved: body weight (n=4, 100%; from -1.79 kg 95% CI -3.17 to -0.41; P=.01 to -2.80 kg 95% CI -4.54 to -1.06, P=.002), BMI (n=1, 25%; -0.64 kg/m2, 95% CI -1.09 to -0.18; P=.01), waist circumference (n=1, 25%; -2.46 cm, 95% CI -4.56 to -0.36; P=.02), systolic/diastolic BP (n=1, 25%; -4.22/-2.87 mm Hg, 95% CI -6.54 to -1.91/ -4.44 to -1.29; P<.01), and HbA1c (n=1, 25%; -0.43%, 95% CI -0.68 to -0.19; P<.001) decreased. PA and PA+Diet apps appear to be most consistent in improving PA and anthropometric measures with favorable but less consistent effects on other CVD risk factors. Future studies are needed that directly compare and better quantify the effects of PA and PA+Diet apps on CVD risk factors. PROSPERO CRD42023392359; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392359.