Vaccines and cardiovascular outcomes: lessons learned from influenza epidemics.

Cardiovascular disease (CVD) is the leading cause of death in the world and is largely preventable. An increasing amount of evidence suggests that annual influenza vaccination reduces CVD-related morbidity and mortality. Despite various clinical guidelines recommending annual influenza vaccination for the general population for influenza-like illness risk reduction, with a particular emphasis on people with CVD, vaccination rates fall consistently below the goal established by the World Health Organization. This review outlines the importance of influenza vaccination, mechanisms of cardiovascular events in influenza, summarizing the available literature on the effects of influenza vaccine in CVD and the benefits of influenza vaccine during the COVID-19 pandemic.

Clinical and Economic Profile of Homeless Young Adults with Stroke in the United States, 2002-2017.

Homelessness is a major social determinant of health. We studied the clinical and economic profile of homeless young adults hospitalized with stroke. We studied the National Inpatient Sample database (2002-2017) to evaluate trends of stroke hospitalization, clinical outcomes, and health expenditure in homeless vs non-homeless young adults (<45 years). We identified 3134 homeless individuals out of 648,944 young adults. Homeless patients were more likely to be men, Black adults and had a higher prevalence of cardiometabolic risk factors and psychiatric disorders than non-homeless adults. Both homeless and non-homeless adults had a similar prevalence of ischemic and hemorrhagic stroke. Between 2002 and 2017, hospitalization rates per million increased for both non-homeless (295.8-416.8) and homeless adults (0.5-3.6) (P ≤ 0.01). Between 2003 and 2017, the decline in in-hospital mortality was limited to non-homeless adults (11%-9%), while it has increased in homeless adults (3%-11%) (P < 0.01). The prevalence of acute myocardial infarction (6.8% vs 3.3%, P < 0.01), and acute kidney injury (13.1% vs 9.4%, P < 0.01) was also higher in homeless vs. non-homeless adults. The length of stay and inflation-adjusted care cost were comparable between both study groups. Finally, a higher proportion of homeless patients left the hospital against medical advice than non-homeless adults. Homeless young stroke patients had significant comorbidities, increased hospitalization rates, and adverse clinical outcomes. Therefore, public health interventions should focus on multidisciplinary care to reduce health care disparities among young homeless adults.

PCSK9 inhibitors and ezetimibe with or without statin therapy for cardiovascular risk reduction: a systematic review and network meta-analysis.

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.

Cardiovascular Disease Mortality Among Hispanic Versus Non-Hispanic White Adults in the United States, 1999 to 2018.

Background Life expectancy has been higher for Hispanic versus non-Hispanic White (NHW) individuals; however, data are limited on cardiovascular disease (CVD) mortality. Method and Results Using the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research death certificate database (1999-2018), we compared age-adjusted mortality rates for total CVD and its subtypes (ischemic heart disease, stroke, heart failure, hypertensive heart disease, other CVD), and average annual percentage changes among Hispanic and NHW adults. The age-adjusted mortality rate per 100 000 was lower for Hispanic than NHW adults for total CVD (186.4 versus 254.6; P<0.001) and its subtypes. Between 1999 and 2018, mortality decline was higher in Hispanic than NHW adults for total CVD (average annual percentage change [AAPC], -2.90 versus -2.41) and ischemic heart disease (AAPC: -4.44 versus -3.82) (P<0.001). In contrast, stroke mortality decline was slower in Hispanic versus NHW adults (AAPC: -2.05 versus -2.60; P<0.05). Stroke mortality increased in Hispanic but stalled in NHW adults since 2011 (AAPC: 0.79 versus -0.09). For ischemic heart disease (AAPC: -0.80 versus -1.85) and stroke (AAPC: -1.32 versus -1.43) mortality decline decelerated more for Hispanic than NHW adults aged <45 years (P<0.05). For heart failure, Hispanic adults aged <45 (3.55 versus 2.16) and 45 to 64 (1.88 versus 1.54) showed greater rise in age-adjusted mortality rate than NHW individuals (P<0.05). Age-adjusted heart failure mortality rate also accelerated in Hispanic versus NHW men (1.00 versus 0.67; P<0.001). Conclusions Disaggregating data by CVD subtype and demographics unmasked heterogeneities in CVD mortality between Hispanic and NHW adults. NHW adults had greater CVD mortality rates and slower decline than Hispanic adults, whereas marked demographic differences in mortality signaled concerning trends among the Hispanic versus NHW population.

A comparative analysis of premature heart disease- and cancer-related mortality in women in the USA, 1999-2018.

AIMS: To compare premature heart disease- and cancer-related deaths in women in the USA. METHODS AND RESULTS: We analysed the US national database of death certificates of women aged <65 from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database between 1999 and 2018. We measured annual percentage changes (APCs) in age-adjusted mortality rates (AAMRs) and years of potential life lost per 100 000 persons due to heart disease and cancer. Overall, cancer was a more prevalent cause of premature death compared with heart disease. Between 1999 and 2018, the AAMRs decreased for both cancer (61.9/100 000 to 45.6/100 000) and heart disease (29.2/100 000 to 22.6/100 000). However, while APC in AAMR for cancer declined consistently over time, after an initial decline, APC in AAMR for heart disease increased between 2010 and 2018 [0.53 95% confidence interval (0.18-0.89)], with a significant rise in Midwest, medium/small metros, and rural areas after 2008. Compared with cancer, APC in AAMR for heart disease increased in women aged 25-34 years [2.24 (0.30-4.22); 2013-18) and 55-64 years [0.46 (0.13-0.80); 2009-13], as well as Non-Hispanic (NH) Whites [APC, 0.79 (0.46-1.13); 2009-18] and NH American Indian/Alaskan Native [2.71 (0.59-4.87); 2011-2018]. Consequently, the mortality gap between cancer and heart disease has narrowed from an AAMR of 32.7/100 000 to 23.0/100 000. CONCLUSIONS: The mortality gap between cancer and heart disease is decreasing among women <65 years. Intensive cardiovascular health interventions are required focusing on vulnerable young demographic subgroups and underserved regional areas to meet the American Heart Association's Impact Goal and Million Hearts Initiative.

Side effects of messenger RNA vaccines and prior history of COVID-19, a cross-sectional study.

BACKGROUND: There are concerns regarding immunogenicity with coronavirus disease 2019 (COVID-19) mRNA vaccines among persons with prior history of COVID-19 (PHC). This study was to analyze the short-term side effects of mRNA vaccines among health care workers (HCWs) with and without PHC. METHODS: A cross-sectional study was performed using an independent online survey questionnaire that gathered responses from HCWs. RESULTS: Among 1,475 HCWs, 1268 (85.97%) completed the survey, 102/1268 (44/447 in Moderna group and 58/821 in Pfizer-BioNTech group) reported PHC during pre-vaccination period. Symptoms of flushing/P = .05, brain fogging/P= .005, vertigo/P= .041, numbness/P= .023, diarrhea/P= .047, hives/P= .028, itching/P= .028, swelling of lips/mouth/P= .001, shortness of breath/P= .022, and anxiety/P= .048 have greater occurrence among Pfizer-BioNtech group with PHC when compared to Pfizer-BioNtech group with no PHC. Symptoms of chills/P= .027, flushing/P= .045, tremor/P= .05, muscle spasm/P= .039, vomiting/P= .031, diarrhea/P= .015, and cough/P= .011 have higher occurrence among Moderna group with PHC when compared to Moderna group with no PHC. CONCLUSIONS: Few short-term side effects among mRNA vaccine recipients with PHC may have necessitated transient time-off from work. The PHC can be considered as a predictor for severity of side effects. While the vaccination program continues in the United States, a future COVID legislation that mandates vaccination among employees along with paid time off provision may help with higher compliance and acceptance.

Stroke-Related Mortality in the United States-Mexico Border Area of the United States, 1999 to 2018.

BACKGROUND The United States (US)-Mexico border is a socioeconomically underserved area. We sought to investigate whether stroke-related mortality varies between the US border and nonborder counties. METHODS AND RESULTS We used death certificates from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to examine stroke-related mortality in border versus nonborder counties in California, Texas, New Mexico, and Arizona. We measured average annual percent changes (AAPCs) in age-adjusted mortality rates (AAMRs) per 100 000 between 1999 and 2018. Overall, AAMRs were higher for nonborder counties, older adults, men, and non-Hispanic Black adults than their counterparts. Between 1999 and 2018, AAMRs reduced from 55.8 per 100 000 to 34.4 per 100 000 in the border counties (AAPC, -2.70) and 64.5 per 100 000 to 37.6 per 100 000 in nonborder counties (AAPC, -2.92). The annual percent change in AAMR initially decreased, followed by stagnation in both border and nonborder counties since 2012. The AAPC in AAMR decreased in all 4 states; however, AAMR increased in California's border counties since 2012 (annual percent change, 3.9). The annual percent change in AAMR decreased for older adults between 1999 and 2012 for the border (-5.10) and nonborder counties (-5.01), followed by a rise in border counties and stalling in nonborder counties. Although the AAPC in AAMR decreased for both sexes, the AAPC in AAMR differed significantly for non-Hispanic White adults in border (-2.69) and nonborder counties (-2.86). The mortality decreased consistently for all other ethnicities/races in both border and nonborder counties. CONCLUSIONS Stroke-related mortality varied between the border and nonborder counties. Given the substantial public health implications, targeted interventions aimed at vulnerable populations are required to improve stroke-related outcomes in the US-Mexico border area.

Effects of Influenza Vaccine on Mortality and Cardiovascular Outcomes in Patients With Cardiovascular Disease: A Systematic Review and Meta-Analysis.

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.

Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril.

Guidelines recommend combining ß-blockers and angiotensin-converting enzyme (ACE) inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit has not been determined. After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study in which carvedilol (C, 20 then 40 mg/day) or a control renin-angiotensin blocker, valsartan (V, 160 then 320 mg/day) were added to L. Ambulatory blood pressure (ABP) and heart rate monitoring was performed at the end of each period. Rate-pressure product (RPP, systolic BP × heart rate, an indicator of cardiac oxygen consumption) was measured over 24 hours, daytime (6 am to midnight), and nighttime (midnight to 6 am) periods. Variability (standard deviation and range) of RPP, BP, and heart rate was also investigated. After 4 weeks, mean 24-hour systolic BP was about 8 mm Hg lower when either V or C was added to L (P < .01 each). Heart rate was consistently lower with C (8 beats/min over 24 hours, P < .000) but was slightly increased with V (about 2 beats/min, P = NS). Consequently, C lowered RPP to a greater degree than V over 24 hours (about 8% vs. 2%, P < .000) and during daytime and nighttime periods (P < .000 each). In addition, RPP variability (SD but not range) was consistently lower on C than V. When added to L, C reduces the mean and variability (SD) of 24-hour heart rate and cardiac workload to a greater degree than valsartan. These effects may contribute to the outcome benefits observed with ß-blocker-ACE inhibitor combinations.