The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B₆, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low– to moderate-certainty evidence). Suboptimal quality and certainty of evidence. Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. None.

Background: Influenza infection causes considerable morbidity and mortality in patients with cardiovascular disease. We assessed the effects of the influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Methods and Results: We searched PubMed, Embase, and the Cochrane Library through January 2020 for randomized controlled trials and observational studies assessing the effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease. Estimates were reported as random effects risk ratios (RRs) with 95% CIs. Analyses were stratified by study design into randomized controlled trials and observational studies. A total of 16 studies (n=237 058), including 4 randomized controlled trials (n=1667) and 12 observational studies (n=235 391), were identified. Participants' mean age was 69.2±7.01 years, 36.6% were women, 65.1% had hypertension, 31.1% had diabetes mellitus, and 23.4% were smokers. At a median follow‐up duration of 19.5 months, influenza vaccine was associated with a lower risk of all‐cause mortality (RR, 0.75; 95% CI, 0.60–0.93 [ P =0.01]), cardiovascular mortality (RR, 0.82; 95% CI, 0.80–0.84 [ P <0.001]), and major adverse cardiovascular events (RR, 0.87; 95% CI, 0.80–0.94 [ P <0.001]) compared with control. The use of the influenza vaccine was not associated with a statistically significant reduction of myocardial infarction (RR, 0.73; 95% CI, 0.49–1.09 [ P =0.12]) compared with control. Conclusions: Data from both randomized controlled trials and observational studies support the use of the influenza vaccine in adults with cardiovascular disease to reduce mortality and cardiovascular events, as currently supported by clinical guidelines. Clinicians and health systems should continue to promote the influenza vaccine as part of comprehensive secondary prevention.

Background: Substantial differences exist between United States counties with regards to premature (<65 years of age) cardiovascular disease (CVD) mortality. Whether underlying social vulnerabilities of counties influence premature CVD mortality is uncertain. Methods: In this cross-sectional study (2014–2018), we linked county-level CDC/ATSDR SVI (Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index) data with county-level CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research) mortality data. We calculated scores for overall SVI and its 4 subcomponents (ie, socioeconomic status; household composition and disability; minority status and language; and housing type and transportation) using 15 social attributes. Scores were presented as percentile rankings by county, further classified as quartiles on the basis of their distribution among all US counties (1st [least vulnerable] = 0 to 0.25; 4th [most vulnerable = 0.75 to 1.00]). We grouped age-adjusted mortality rates per 100 000 person-years for overall CVD and its subtypes (ischemic heart disease, stroke, hypertension, and heart failure) for nonelderly (<65 years of age) adults across SVI quartiles. Results: Overall, the age-adjusted CVD mortality rate per 100 000 person-years was 47.0 (ischemic heart disease, 28.3; stroke, 7.9; hypertension, 8.4; and heart failure, 2.4). The largest concentration of counties with more social vulnerabilities and CVD mortality were clustered across the southwestern and southeastern parts of the United States. The age-adjusted CVD mortality rates increased in a stepwise manner from 1st to 4th SVI quartiles. Counties in the 4th SVI quartile had significantly higher mortality for CVD (rate ratio, 1.84 [95% CI, 1.43–2.36]), ischemic heart disease (1.52 [1.09–2.13]), stroke (2.03 [1.12–3.70]), hypertension (2.71 [1.54–4.75]), and heart failure (3.38 [1.32–8.61]) than those in the 1st SVI quartile. The relative risks varied considerably by demographic characteristics. For example, among all ethnicities/races, non-Hispanic Black adults in the 4th SVI quartile versus the 1st SVI quartile exclusively had significantly higher relative risks of stroke (1.65 [1.07–2.54]) and heart failure (2.42 [1.29–4.55]) mortality. Rural counties with more social vulnerabilities had 2- to 5-fold higher mortality attributable to CVD and subtypes. Conclusions: In this analysis, US counties with more social vulnerabilities had higher premature CVD mortality, varied by demographic characteristics and rurality. Focused public health interventions should address the socioeconomic disparities faced by underserved communities to curb the growing burden of premature CVD.

Objective To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant. Design Network meta-analysis. Data sources Medline, EMBASE, and Cochrane Library up to 31 December 2020. Eligibility criteria for selecting studies Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months. Main outcome measures We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke. Results We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke. Conclusions Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.

To assess whether continuous positive airway pressure (CPAP) therapy reduces major adverse cardiovascular events (MACE) in patients with moderate-to-severe obstructive sleep apnoea (OSA). A total of 235 articles were recovered using MEDLINE, EMBASE and Cochrane library (inception–December 2016) and references contained in the identified articles. Seven randomized controlled trials (RCTs) were selected for final analysis. Analysis of 4268 patients demonstrated non-significant 26% relative risk reduction in MACE with CPAP [risk ratio (RR) 0.74; 95% confidence interval (CI) 0.47–1.17; P = 0.19, I² = 48%]. A series of sensitivity analyses suggested that increased CPAP usage time yielded significant risk reduction in MACE. and stroke. Subgroup analysis revealed that CPAP adherence time ≥4 hours (h)/night reduced the risk of MACE by 57% (RR 0.43; 95% CI 0.23–0.80; P = 0.01, I² = 0%). CPAP therapy showed no beneficial effect on myocardial infarction (MI), all-cause mortality, atrial fibrillation/flutter (AF), or heart failure (HF) (P > 0.05). CPAP had positive effect on mood and reduced the daytime sleepiness [Epworth Sleepiness Scale (ESS): mean difference (MD) −2.50, 95% CI − 3.62, −1.39; P < 0.001, I² = 81%]. CPAP therapy might reduce MACE and stroke among subjects with CPAP time exceeding 4 h/night. Additional randomized trials mandating adequate CPAP time adherence are required to confirm this impression.

Background: Social and environmental factors play an important role in the rising health care burden of cardiovascular disease. The Centers for Disease Control and Prevention developed the Social Vulnerability Index (SVI) from US census data as a tool for public health officials to identify communities in need of support in the setting of a hazardous event. SVI (ranging from a least vulnerable score of 0 to a most vulnerable score of 1) ranks communities on 15 social factors including unemployment, minoritized groups status, and disability, and groups them under 4 broad themes: socioeconomic status, housing and transportation, minoritized groups, and household composition. We sought to assess the association of SVI with self‐reported prevalent cardiovascular comorbidities and atherosclerotic cardiovascular disease (ASCVD). Methods and Results: We performed a retrospective cohort analysis of adults (≥18 years) in the Behavioral Risk Factor Surveillance System 2016 to 2019. Data regarding self‐reported prevalent cardiovascular comorbidities (including diabetes, hypertension, hyperlipidemia, smoking, substance use), and ASCVD was captured using participants' response to a structured telephonic interview. We divided states on the basis of the tertile of SVI (first—participant lives in the least vulnerable group of states, 0–0.32; to third—participant lives in the most vulnerable group of states, 0.54–1.0). Multivariable logistic regression models adjusting for age, race and ethnicity, sex, employment, income, health care coverage, and association with federal poverty line were constructed to assess the association of SVI with cardiovascular comorbidities. Our study sample consisted of 1 745 999 participants ≥18 years of age. States in the highest (third) tertile of social vulnerability had predominantly Black and Hispanic adults, lower levels of education, lower income, higher rates of unemployment, and higher rates of prevalent comorbidities including hypertension, diabetes, chronic kidney disease, hyperlipidemia, substance use, and ASCVD. In multivariable logistic regression models, individuals living in states in the third tertile of SVI had higher odds of having hypertension (odds ratio (OR), 1.14 [95% CI, 1.11–1.17]), diabetes (OR, 1.12 [95% CI, 1.09–1.15]), hyperlipidemia (OR, 1.09 [95% CI, 1.06–1.12]), chronic kidney disease (OR, 1.17 [95% CI, 1.12–1.23]), smoking (OR, 1.05 [95% CI, 1.03–1.07]), and ASCVD (OR, 1.15 [95% CI, 1.12–1.19]), compared with those living in the first tertile of SVI. Conclusions: SVI varies across the US states and is associated with prevalent cardiovascular comorbidities and ASCVD, independent of age, race and ethnicity, sex, employment, income, and health care coverage. SVI may be a useful assessment tool for health policy makers and health systems researchers examining multilevel influences on cardiovascular‐related health behaviors and identifying communities for targeted interventions pertaining to social determinants of health.