Total Cardiovascular Disease Events Research Articles

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Cardiovascular events risk in office-masked nocturnal hypertension defined by home blood pressure monitoring: the J-HOP nocturnal blood pressure study

Abstract Background Elevated nocturnal home blood pressure (BP) has been reported to be associated with increased risk for cardiovascular disease (CVD). Masked hypertension defined by home BP monitoring is also a strong risk factor for adverse CVD outcomes. However, no study has investigated the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk. Purpose This study aimed to examine the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk in a clinical practice-based population. Methods This was a prospective observational study including Japanese participants with CVD or high risk of CVD. Three office BPs were taken on two different occasions. Nocturnal home BP was measured three times per night for two weeks. The association between office-masked nocturnal hypertension and incident total CVD events (including fatal and non-fatal stroke and coronary heart disease) was examined using Cox regression. Results 2,545 participants were followed for the mean of 7.1 years (18,116 person-years), during which 152 (6.0%) CVD events occurred. Mean age (standard deviation) was 63.3 (10.3) years; 49.0% were male; 82.6% took antihypertensive medications. The proportions of participants with normotension (office BP <140/90 mmHg and nocturnal home BP <120/70 mmHg), white-coat hypertension (office BP ≥140/90 mmHg and nocturnal home BP <120/70 mmHg), office-masked nocturnal hypertension (office BP <140/90 mmHg and nocturnal home BP ≥120/70 mmHg), and sustained hypertension (office BP ≥140/90 mmHg and nocturnal home BP ≥120/70 mmHg) were 25.3%, 14.4%, 23.2%, and 37.1%, respectively. The office-masked nocturnal hypertensive group and sustained hypertensive group had higher incidence rates of total CVD events compared with the normotensive group. Relative to normotension, those with both office-masked nocturnal hypertension (adjusted hazard ratio [aHR] 1.72, 95% confidence interval [CI] 1.01–2.92) and sustained hypertension (aHR 1.75, 95%CI 1.03–2.96) had similarly increased CVD risk, even after adjustment for daytime home BP values. Conclusions Screening for office-masked nocturnal hypertension with home BP monitoring identifies a potentially important group of patients with increased risk for incident CVD events for whom additional preventative measures may be appropriate.

Effects of insulin resistance and β-cell function on diabetic complications in Korean diabetic patients.

Diabetes mellitus is characterized by insulin resistance (IR) and dysfunctional insulin secretion from pancreatic β-cells. However, little research has been conducted on the relationship between IR and β-cell function in relation to diabetic complications among Korean diabetic patients. This study aimed to examine the differential associations between IR and β-cell function and various diabetic complications among Korean diabetic patients. The analysis employed a common data model (CDM). IR and β-cell function were quantified using the homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β), respectively. Hazard ratios for diabetic nephropathy, diabetic retinopathy, and cardiovascular disease (CVD) events were calculated. The study cohort consisted of 2,034 diabetic patients aged over 20 years who visited EUMC between January 2001 and December 2019. Among diabetic patients in the highest quartile of HOMA-IR, the adjusted hazard ratio for total CVD events was 1.76 (95% confidence interval [CI], 1.20-2.57) compared with those in the lowest quartile of HOMA-IR (P = 0.004). In contrast, diabetic patients in the lowest quartile of HOMA-β exhibited an adjusted hazard ratio of 3.91 (95% CI, 1.80-8.49) for diabetic retinopathy compared to those in the highest quartile of HOMA-β (P = 0.001). Insulin resistance and β-cell function exhibited different associations with diabetic complications among Korean diabetic patients. Specifically, lower β-cell function was associated with an increased risk of diabetic retinopathy, whereas higher IR was associated with an increased risk of CVD events. Individuals with pronounced IR should prioritize CVD prevention measures, and those with significant β-cell dysfunction may benefit from early, intensive surveillance for diabetic retinopathy.

Relationships between APOE, Type 2 Diabetes, and Cardiovascular Disease in Postmenopausal Women.

The Apolipoprotein E (APOE) ε4 allele, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) are well-established risk factors for dementia. Relationships between APOE and incidence of T2DM and CVD are not fully understood but may shed light on the mechanisms underlying dementia pathogenesis. Postmenopausal women (N=6,795) from the Women's Health Initiative hormone therapy clinical trial with APOE genotyping and no prior diagnosis of T2DM or CVD were included. We examined associations of APOE status (APOE2+ [ε2/ε2, ε2/ε3], APOE3 [ε3/ε3], and APOE4+ [ε4/ε4, ε3/ε4] carriers) with incidence of T2DM, coronary heart disease (CHD), stroke, and total CVD events using Cox regression. CVD outcomes were examined in baseline non-statin users and adjusted for statin initiation over follow-up to account for possible confounding by statins. Among all participants (mean age 66.7±6.5 years, 100% non-Hispanic white), 451 (6.6%) were using statins at baseline. Over the follow-up (mean 14.9 and 16.0 years for T2DM and CVD, respectively), 1,564 participants developed T2DM and 1,578 developed CVD. T2DM incidence did not differ significantly by APOE status (ps≥0.09). Among non-statin users, APOE4+ had higher incidence of total CVD (hazard ratio [95% confidence interval]=1.18 [1.02-1.38], p=0.03) compared to APOE3 carriers, but risks for CHD (1.09 [0.87-1.36], p=0.47) and stroke (1.14 [0.91-1.44], p=0.27) were not significantly elevated when examined individually. CVD outcomes did not differ between APOE2+ and APOE3 carriers (ps≥0.11). T2DM risk did not differ by APOE status among postmenopausal women, but APOE4+ carriers not using statins had an increased risk of total CVD events.

Effectiveness of Hypertension Management Strategies in SPRINT-Eligible US Adults: ASimulation Study.

Despite reducing cardiovascular disease (CVD) events and death in SPRINT (Systolic Blood Pressure Intervention Trial), intensive systolic blood pressure goals have not been adopted in the United States. This study aimed to simulate the potential long-term impact of 4 hypertension management strategies in SPRINT-eligible US adults. The validated Blood Pressure Control-Cardiovascular Disease Policy Model, a discrete event simulation of hypertension care processes (ie, visit frequency, blood pressure [BP] measurement accuracy, medication intensification, and medication adherence) and CVD outcomes, was populated with 25 000 SPRINT-eligible US adults. Four hypertension management strategies were simulated: (1) usual care targeting BP <140/90 mm Hg (Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care), (2) intensive care per the SPRINT protocol targeting BP <120/90 mm Hg (SPRINT intensive), (3) usual care targeting guideline-recommended BP <130/80 mm Hg (American College of Cardiology/American Heart Association usual care), and (4) team-based care added to usual care and targeting BP <130/80 mm Hg. Relative to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, among the 18.1 million SPRINT-eligible US adults, an estimated 138 100 total CVD events could be prevented per year with SPRINT intensive, 33 900 with American College of Cardiology/American Heart Association usual care, and 89 100 with team-based care. Compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure usual care, SPRINT intensive care was projected to increase treatment-related serious adverse events by 77 600 per year, American College of Cardiology/American Heart Association usual care by 33 300, and team-based care by 27 200. As BP control has declined in recent years, health systems must prioritize hypertension management and invest in effective strategies. Adding team-based care to usual care may be a pragmatic way to manage risk in this high-CVD-risk population.

Development and Validation of the American Heart Association's PREVENT Equations.

Multivariable equations are recommended by primary prevention guidelines to assess absolute risk of cardiovascular disease (CVD). However, current equations have several limitations. Therefore, we developed and validated the American Heart Association Predicting Risk of CVD EVENTs (PREVENT) equations among US adults 30 to 79 years of age without known CVD. The derivation sample included individual-level participant data from 25 data sets (N=3 281 919) between 1992 and 2017. The primary outcome was CVD (atherosclerotic CVD and heart failure). Predictors included traditional risk factors (smoking status, systolic blood pressure, cholesterol, antihypertensive or statin use, and diabetes) and estimated glomerular filtration rate. Models were sex-specific, race-free, developed on the age scale, and adjusted for competing risk of non-CVD death. Analyses were conducted in each data set and meta-analyzed. Discrimination was assessed using the Harrell C-statistic. Calibration was calculated as the slope of the observed versus predicted risk by decile. Additional equations to predict each CVD subtype (atherosclerotic CVD and heart failure) and include optional predictors (urine albumin-to-creatinine ratio and hemoglobin A1c), and social deprivation index were also developed. External validation was performed in 3 330 085 participants from 21 additional data sets. Among 6 612 004 adults included, mean±SD age was 53±12 years, and 56% were women. Over a mean±SD follow-up of 4.8±3.1 years, there were 211 515 incident total CVD events. The median C-statistics in external validation for CVD were 0.794 (interquartile interval, 0.763-0.809) in female and 0.757 (0.727-0.778) in male participants. The calibration slopes were 1.03 (interquartile interval, 0.81-1.16) and 0.94 (0.81-1.13) among female and male participants, respectively. Similar estimates for discrimination and calibration were observed for atherosclerotic CVD- and heart failure-specific models. The improvement in discrimination was small but statistically significant when urine albumin-to-creatinine ratio, hemoglobin A1c, and social deprivation index were added together to the base model to total CVD (ΔC-statistic [interquartile interval] 0.004 [0.004-0.005] and 0.005 [0.004-0.007] among female and male participants, respectively). Calibration improved significantly when the urine albumin-to-creatinine ratio was added to the base model among those with marked albuminuria (>300 mg/g; 1.05 [0.84-1.20] versus 1.39 [1.14-1.65]; P=0.01). PREVENT equations accurately and precisely predicted risk for incident CVD and CVD subtypes in a large, diverse, and contemporary sample of US adults by using routinely available clinical variables.

Low-dose aspirin in the primary prevention of cardiovascular diseases: A retrospective, propensity score matched study

Background and aimsAlthough the guidelines have been revised recently, the effect of aspirin for the primary prevention of cardiovascular disease (CVD) is still controversial. Thus, we aimed to evaluate the effect of aspirin on primary prevention in the real world. MethodsAmong the 4,266,268 participants without a history of CVD or previous prescription of aspirin and other antiplatelet agents who were screened between 2002 and 2008, 268,963 persons who were prescribed low-dose aspirin (≤100 mg/day) over 90 days in 2002–2008 and 1,075,852 persons who did not receive aspirin were selected after propensity score matching. A Cox proportional-hazards model was used to evaluate the effect of low-dose aspirin on the development of CVD and bleeding episodes. ResultsAspirin showed a protective effect on total CVD events (hazard ratio (HR); 0.737, 95% confidence interval; 0.729–0.745). The protective effect of aspirin on total CVD events was significant in men, women and even in young participants (<65 years). Aspirin had a protective effect in participants with diabetes or hypertension against all subcategories of CVD. The HR of bleeding risk was 1.4–1.5 in aspirin group. ConclusionsLow-dose aspirin generally showed a protective effect against CVD regardless of age, sex, and underlying comorbidities in the real world. Though, the effect of aspirin was evident at a young age, the risk of bleeding was also high (1.4–1.5 times), and thus, careful prescription is required.

Abstract P523: Joint Improvement Scale of Loneliness and Traditional Risk Factor Control, and Incident Cardiovascular Disease in Diabetes Patients

Background: Emerging evidence has shown a higher rate of loneliness and social isolation among patients with diabetes, and loneliness and isolation has been associated with high risk of cardiovascular disease (CVD). Hypothesis: We investigated the extent to which the risks of CVDs could be lowered by improvement of loneliness and social isolation, individually or in conjunction with controlling traditional risk factors in diabetic patients. Methods: A total of 18,783 participants diagnosed with diabetes from the UK Biobank were included. A two-item scale and a three-item scale were used to assess the improvement of loneliness and isolation status, respectively. The degree of traditional risk-factor control was defined as the number of glycated hemoglobin (HbA1c), blood pressure (BP), low-density-lipoprotein cholesterol (LDL-C), smoking and microalbumin reaching the target range. Results: During a mean follow-up of 10.7 years, 3,129 incident total CVD events were documented, including 2,627 coronary heart disease (CHD) and 721 stroke. We found that each point increase in loneliness improvement scale was significantly associated with an 11% lower risk of CVD (HR, 95%CI, 0.89, 0.84-0.93) and a 12% lower risk of CHD (HR, 95%CI, 0.88, 0.83-0.93), but not with stroke. The improvement scale of social isolation was not associated with CVDs. Loneliness showed greater relative importance than lifestyle risk factors in preventing CVD among diabetic patients. We found a significant additive interaction between loneliness and the degree of traditional risk-factor control on the risk of CVDs ( P for additive interaction=0.002). Moreover, compared with non-diabetes controls, the diabetes-related excess CVD risk might be eliminated when three or more risk factors were controlled in non-lonely patients, but more than four are required in lonely patients. Conclusion: Among diabetes patients, improvement of loneliness is associated with a lower risk of CVD and shows an additive interaction with traditional risk factor control.

Adding Salt to Foods and Risk of Cardiovascular Disease

BackgroundWe recently found that the frequency of adding salt to foods could reflect a person’s long-term salt taste preference and sodium intake, and was significantly related to life expectancy. ObjectiveWe analyzed whether the frequency of adding salt to foods was associated with incident cardiovascular disease (CVD) risk. MethodsThis study included 176,570 adults in UK Biobank who were initially free of CVD. Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and incident CVD events. ResultsDuring a median of 11.8 years of follow-up, 9,963 total CVD events, 6,993 ischemic heart disease (IHD) cases, 2,007 stroke cases, and 2,269 heart failure cases were documented. Lower frequency of adding salt to foods was significantly associated with lower risk of total CVD events after adjustment for covariates and the DASH (Dietary Approaches to Stop Hypertension) diet (a modified DASH score was used without considering sodium intake). Compared with the group of always adding salt to foods, the adjusted HRs were 0.81 (95% CI: 0.73-0.90), 0.79 (95% CI: 0.71-0.87), and 0.77 (95% CI: 0.70-0.84) across the groups of usually, sometimes, and never/rarely, respectively (P trend < 0.001). Among the subtypes of CVD, adding salt showed the strongest association with heart failure (P trend <0.001), followed by IHD (P trend < 0.001), but was not associated with stroke. We found that participants who combined a DASH-style diet with the lowest frequency of adding salt had the lowest CVD risk. ConclusionsOur findings indicate that lower frequency of adding salt to foods is associated with lower risk of CVD, particularly heart failure and IHD.

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study

ObjectiveTo determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort. MethodsNational Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index. ResultsThere were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63). ConclusionNo increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.

Temporal trends in associations between severe mental illness and risk of cardiovascular disease: A systematic review and meta-analysis.

BackgroundSevere mental illness (SMI; schizophrenia, bipolar disorders (BDs), and other nonorganic psychoses) is associated with increased risk of cardiovascular disease (CVD) and CVD-related mortality. To date, no systematic review has investigated changes in population level CVD-related mortality over calendar time. It is unclear if this relationship has changed over time in higher-income countries with changing treatments.Methods and findingsTo address this gap, a systematic review was conducted, to assess the association between SMI and CVD including temporal change. Seven databases were searched (last: November 30, 2021) for cohort or case–control studies lasting ≥1 year, comparing frequency of CVD mortality or incidence in high-income countries between people with versus without SMI. No language restrictions were applied. Random effects meta-analyses were conducted to compute pooled hazard ratios (HRs) and rate ratios, pooled standardised mortality ratios (SMRs), pooled odds ratios (ORs), and pooled risk ratios (RRs) of CVD in those with versus without SMI. Temporal trends were explored by decade. Subgroup analyses by age, sex, setting, world region, and study quality (Newcastle–Ottawa scale (NOS) score) were conducted. The narrative synthesis included 108 studies, and the quantitative synthesis 59 mortality studies (with (≥1,841,356 cases and 29,321,409 controls) and 28 incidence studies (≥401,909 cases and 14,372,146 controls). The risk of CVD-related mortality for people with SMI was higher than controls across most comparisons, except for total CVD-related mortality for BD and cerebrovascular accident (CVA) for mixed SMI. Estimated risks were larger for schizophrenia than BD. Pooled results ranged from SMR = 1.55 (95% confidence interval (CI): 1.33 to 1.81, p < 0.001), for CVA in people with BD to HR/rate ratio = 2.40 (95% CI: 2.25 to 2.55, p < 0.001) for CVA in schizophrenia. For schizophrenia and BD, SMRs and pooled HRs/rate ratios for CHD and CVD mortality were larger in studies with outcomes occurring during the 1990s and 2000s than earlier decades (1980s: SMR = 1.14, 95% CI: 0.57 to 2.30, p = 0.71; 2000s: SMR = 2.59, 95% CI: 1.93 to 3.47, p < 0.001 for schizophrenia and CHD) and in studies including people with younger age. The incidence of CVA, CVD events, and heart failure in SMI was higher than controls. Estimated risks for schizophrenia ranged from HR/rate ratio 1.25 (95% CI: 1.04 to 1.51, p = 0.016) for total CVD events to rate ratio 3.82 (95% CI: 3.1 to 4.71, p < 0.001) for heart failure. Incidence of CHD was higher in BD versus controls. However, for schizophrenia, CHD was elevated in higher-quality studies only. The HR/rate ratios for CVA and CHD were larger in studies with outcomes occurring after the 1990s. Study limitations include the high risk of bias of some studies as they drew a comparison cohort from general population rates and the fact that it was difficult to exclude studies that had overlapping populations, although attempts were made to minimise this.ConclusionsIn this study, we found that SMI was associated with an approximate doubling in the rate ratio of CVD-related mortality, particularly since the 1990s, and in younger groups. SMI was also associated with increased incidence of CVA and CHD relative to control participants since the 1990s. More research is needed to clarify the association between SMI and CHD and ways to mitigate this risk.

Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial.

AimsJoint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome).Methods and resultsFINGER enrolled 1259 individuals aged 60–77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51–0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56–1.26) and total CVD events 0.80 (95% CI: 0.61–1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28–0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20–0.81) was lower in the intervention than the control group.ConclusionA 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD.

Longitudinal association of egg intake frequency with cardiovascular disease in Chinese adults

Background and aimsReducing dietary cholesterol is generally acceptable for the prevention of cardiovascular disease (CVD). Eggs are nutrient-dense and common food items across the world, while rich in cholesterol. The potential effects of egg intake on cardiovascular health remain uncertainty and have been under debate in past decades. Methods and resultsA nationwide cohort of 20,688 participants aged 16–110 years without CVD at baseline were derived from the China Family Panel Studies. Egg consumption was assessed by a semi-quantitative food frequency questionnaire. We adopted stratified Cox proportional hazards model with random intercepts for provinces to evaluate associations of egg intake with CVD incidence. During a median follow-up of 6.0 years, we identified 2395 total CVD incidence and mean egg consumption was 3 times/week. Egg intakes were associated lower risks of CVD incidence in the multivariate-adjusted model. Compared with the non-consumers, the corresponding HRs (95% confidence interval) for total CVD events were 0.84 (0.74–0.94) for 1–2 times per week, 0.78 (0.69–0.88) for 3–6/week, and 0.83 (0.72–0.95) for ≥7/week. Similar relationships were found in hypertension. Approximately non-linear relationships were observed between egg consumption with total CVD and hypertension incidence, identifying the lowest risk in 3–6 times/week. Subgroup analyses estimated lower risks of total CVD and hypertension in females only, with significant effect modification by sex (P for interaction = 0.008 and 0.020). ConclusionEgg consumption may be associated with lower risks of CVD incidence among Chinese adults. Our findings could have implications in CVD prevention and might be considered in the development of dietary guidelines.

Association of soy food with cardiovascular outcomes and all-cause mortality in a Chinese population: a nationwide prospective cohort study.

This study aimed to clarify the association of soy intake with cardiovascular disease (CVD) and all-cause mortality. We conducted a prospective cohort study in a Chinese population composed of 97,930 participants aged ≥ 40years old without CVD at baseline in 2011. Habitual soy intake over a period of 12months was evaluated using a food frequency questionnaire. All participants were classified into four groups based on their soy food consumption levels: < 15, 15-29, 30-59, and ≥ 60g/day, with the lowest category as the reference group. Follow-up was conducted between 2014 and 2016 to assess CVD incidence and all-cause mortality since baseline, which was collected from the local mortality and disease registers of the National Disease Surveillance Point System and National Health Insurance System. The Cox proportional hazards regression models were used to analyze the relationship of soy intake with later CVD events and all-cause mortality. During 350,604 person-years of follow-up (median [interquartile range]: 3.16 [2.98, 4.77] years), 2523 total CVD events and 1473 all-cause mortalities were documented. After controlling for covariates, the hazard ratios (95% confidence intervals) for total CVD events across increasing soy intake levels were 1.03 (0.93-1.14); 0.96 (0.86-1.07); and 0.86 (0.75-0.98; p for trend = 0.0434), while those for all-cause mortality were 0.88 (0.77-1.02); 0.86 (0.74-1.00); and 0.83 (0.69-0.99; p for trend = 0.0084). High soy intake was associated with a reduced risk of total CVD events and all-cause mortality among a Chinese population.

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

AimsTo evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes. Data synthesisPubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose–response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes. ConclusionsDrinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results. Registry and registry numberThe protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).

Prognostic Value of Soluble Suppression of Tumorigenicity 2 in Chronic Kidney Disease Patients: A Meta-Analysis.

Objective Previous studies have controversial results about the prognostic role of soluble suppression of tumorigenicity 2 (sST2) in chronic kidney disease (CKD). Therefore, we conduct this meta-analysis to access the association between sST2 and all-cause mortality, cardiovascular disease (CVD) mortality, and CVD events in patients with CKD. Methods The publication studies on the association of sST2 with all-cause mortality, CVD mortality, and CVD events from PubMed and Embase were searched through August 2020. We pooled the hazard ratio (HR) comparing high versus low levels of sST2 and subgroup analysis based on treatment, continent, and diabetes mellitus (DM) proportion, and sample size was also performed. Results There were 15 eligible studies with 11,063 CKD patients that were included in our meta-analysis. Elevated level of sST2 was associated with increased risk of all-cause mortality (HR 2.05; 95% confidence interval (CI), 1.51–2.78), CVD mortality (HR 1.68; 95% CI, 1.35–2.09), total CVD events (HR 1.88; 95% CI, 1.26–2.80), and HF (HR 1.35; 95% CI, 1.11–1.64). Subgroup analysis based on continent, DM percentage, and sample size showed that these factors did not influence the prognostic role of sST2 levels to all-cause mortality. Conclusions Our results show that high levels of sST2 could predict the all-cause mortality, CVD mortality, and CVD events in CKD patients.

REDUCE-IT Eligibility and Preventable Cardiovascular Events in the US Population (from the National Health and Nutrition Examination Survey [NHANES

The reduction of cardiovascular events with icosapent ethyl-intervention (REDUCE-IT) trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl (IPE) reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US adults with available REDUCE-IT inclusion criteria from NHANES Surveys 1999-2016 and estimated primary (CVD death, nonfatal myocardial infarction, stroke, revascularization, or unstable angina) and secondary composite (CVD death, nonfatal MI or stroke) events using REDUCE-IT published event rates in the IPE and placebo groups, the difference being the number of preventable events. From 11,445 adults aged ≥45 years (representing 111.1 million [M]), a total of 319 persons (3.0 M) fit key REDUCE-IT eligibility criteria: triglycerides of 135 to 499 mg/dL, HbA1c <10%, blood pressure <200/100 mm Hg, and on a statin with LDL-C of 40 to 99 mg/dL. 63% had prior CVD and 37% had DM + ≥1 risk factor (primary prevention cohort). If these persons are given IPE for the REDUCE-IT median trial period of 4.9 years, we estimated preventing a total 349,817 (71,391/year) primary CVD outcomes of which 146,011 (29,798/year) were initial events. Most (24,151) preventable events were from the secondary prevention cohort. Using FDA eligibility criteria, an estimated 4.6 million persons would be eligible for IPE, with 60,544 preventable primary CVD outcomes annually from REDUCE-IT USA event rates. In conclusion, many CVD events in US adults with known CVD or DM and well-controlled LDL-C on statin therapy can be prevented with IPE.

Association between Excessive Daytime Sleepiness and Risk of Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis of Longitudinal Cohort Studies

ObjectiveExcessive daytime sleepiness (EDS) is a prevalent phenomenon in adults, and although cohort studies have reported an association between EDS and adverse health outcomes, the results are inconclusive. This meta-analysis summarizes the evidence from longitudinal cohort studies on the relationship between EDS and the risk of cardiovascular disease (CVD) or all-cause mortality. DesignA meta-analysis of prospective cohort studies was conducted. Setting and ParticipantsWe searched for relevant longitudinal cohort studies published through September 2019 using Web of Science, PubMed, Medline, and SciELO. MeasuresThe relative risk (RR) of EDS was pooled in random-effects or fixed-effects meta-analyses. Subgroup, sensitivity, and meta-regression analyses were performed to identify heterogeneous sources. Publication bias was assessed using the Begg and Egger tests. ResultsSeventeen studies (153,909 participants) were included. The mean follow-up was 5.4 (range, 2–13.8) years. The pooled relative risks of EDS were 1.28 [95% confidence interval (CI) 1.09–1.50] for total CVD events, 1.28 (95% CI 1.12–1.46) for coronary heart disease (CHD), 1.52 (95% CI 1.10–2.12) for stroke, 1.47 (95% CI 1.09–1.98) for CVD mortality, and 1.23 (95% CI 1.13–1.33) for all-cause mortality. Subgroup analyses by mean age, region, follow-up time, EDS assessment method, and year of publication yielded similar results. Conclusions and ImplicationsEDS is a modest but statistically significant predictor for CVD events, coronary heart disease, stroke, and CVD and all-cause mortality. However, its prognostic value warrants further investigation to identify those at highest risk of mortality and in need of intervention to improve outcomes.

Icosapent ethyl: drug profile and evidence of reduced residual cardiovascular risk in patients with statin-managed LDL-C cholesterol

ABSTRACT Introduction: Icosapent ethyl (IPE) is a highly purified (>96%) form of eicosapentanoic acid, a marine-derived omega-3 fatty acid known to reduce serum triglyceride (TG) levels. In the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), the addition of 4 g IPE daily resulted in a 25% reduction in cardiovascular events beyond statins and other standard of care therapies. IPE is now the only therapy currently approved by the Food and Drug Administration to treat patients with elevated TGs (150–499 mg/dL) with cardiovascular disease (CVD) or Type 2 diabetes mellitus and two or more CVD risk factors. Areas covered IPE is a highly purified form of eicosapentanoic acid for patients with elevated TGs as monotherapy or combined with statins and/or other lipid lowering therapies. The REDUCE-IT Study demonstrated a 25% reduction in the primary outcome measure and 30% reduction in total CVD events in high-risk patients with elevated TGs (135–499 mg/dL) assigned to IPE (4 g daily). Side effects included a statistically significant increased risk of atrial fibrillation and bleeding, although the risk of stroke was reduced and there were no cases of fatal bleeding. The FDA recently approved IPE for treatment of patients with TG levels of 150–499 mg/dL and preexisting CVD or Type 2 diabetes mellitus with two or more risk factors. Expert opinion IPE has proven to be superior to other forms of omega 3 fatty acid in reducing CVD risk in patients with elevated TG. This could be attributed to multiple factors including the use of highly purified eicosapentaenoic acid ethyl esters without docosahexaenoic acid (DHA), thus preventing the increase in low-density lipoprotein cholesterol associated with DHA especially at high TG levels, reduction in atherogenic TG-rich particles, antioxidant and anti-inflammatory properties, improvement in endothelial function, and stabilization of atherosclerotic plaque.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population

IntroductionDyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.Material and methodsThis prospective cohort study comprised a population of 8698 men and women aged 35–65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.ResultsAfter 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19–2; P-value< 0.01; HR: 1.53; 95% CI: 1.18–1.98; P < 0.01; HR: 1.57; 95% CI: 1.27–2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12–6.57; P-value< 0.05).ConclusionIn the present study, TC baseline level was significantly associated with the risk of MI among men.