Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3)

The substantial decline in cardiovascular-disease (CVD) mortality in high-income countries has underpinned their increasing longevity over the past half-century. However, recent evidence suggests this long-term decline may have stagnated, and even reversed in younger populations. We assess recent CVD-mortality trends in high-income populations and discuss the findings in relation to trends in risk factors. We used vital statistics since 2000 for 23 high-income countries published in the World Health Organization Mortality Database. Age-standardized CVD death rates by sex for all ages, and at ages 35-74 years, were calculated and smoothed using LOWESS regression. Findings were contrasted with the Global Burden of Disease (GBD) Study. The rate of decline in CVD mortality has slowed considerably in most countries in recent years for both males and females, particularly at ages 35-74 years. Based on the latest year of data, the decline in the CVD-mortality rate at ages 35-74 years was <2% (about half the annual average since 2000) for at least one sex in more than half the countries. In North America (US males and females, Canada females), the CVD-mortality rate even increased in the most recent year. The GBD Study estimates, after correcting for misdiagnoses, suggest an even more alarming reversal, with CVD death rates rising in seven countries for at least one sex in 2017. The rate of decline and initial level of CVD mortality appear largely unrelated. A significant slowdown in CVD-mortality decline is now apparent across high-income countries with diverse epidemiological environments. High and increasing obesity levels, limited potential future gains from further reducing already low smoking prevalence, especially in English-speaking countries, and persistent inequalities in mortality risk pose significant challenges for public policy to promote better cardiovascular health.

The effect of physical activity on mortality and cardiovascular disease in 130 000 people from 17 high-income, middle-income, and low-income countries: the PURE study

BackgroundIschemic heart disease and stroke are two severe types of cardiovascular disease (CVD), a major contributor to the global burden of disease. The preventive framework currently includes promotion of both adequate cardiorespiratory and muscular fitness. Although muscle fitness is established as an indicator of health, it is currently unknown whether muscle strength is associated with later CVD independently of cardiorespiratory fitness.MethodsWe studied 38,588 Swedish men who in 1969 to 1970 (typically aged 18 years) completed compulsory conscription. Using the mean standardized score of three isometric muscle strength tests performed at conscription (hand grip, elbow flexion and knee extension), we categorized the subjects into three groups with the 25th to 75th percentile defining the reference category. We followed the cohort until 2012 for diagnosed CVD events and mortality via national health care registers and the national cause of death register. To estimate hazard ratios (HR) for CVD events (coronary heart disease or stroke) and CVD mortality we used Cox proportional hazard models adjusted for body mass index, smoking, alcohol consumption, cardiorespiratory fitness and socioeconomic status.ResultsMen with high muscle strength in adolescence had a decreased risk of later CVD events (HR 0.88, 95% confidence interval 0.77 to 0.99), whereas we observed no increased risk in men with low muscle strength (0.99, 0.86 to 1.13). However, low muscle strength was associated with increased risk of CVD mortality during middle age (1.31, 1.02 to 1.67).ConclusionsMuscle strength in adolescent men is inversely associated with later CVD events and CVD mortality in middle age, independently of cardiorespiratory fitness and other important confounders. Thus, the role of muscle fitness in the prevention and pathogenesis of CVD warrants increased attention.

Objective:To investigate the relationship between body mass index (BMI), waist circumference (WC) or waist–hip ratio (WHR) and all-cause mortality or cause-specific mortality.Design:Cross-sectional surveys linked to hospital admissions and death records.Subjects:In total, 20 117 adults (aged 18–86 years) from a nationally representative sample of the Scottish population.Measurements:Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause, or cause-specific, mortality. The three anthropometric measurements BMI, WC and WHR were the main variables of interest. The following were adjustment variables: age, gender, smoking status, alcohol consumption, survey year, social class and area of deprivation.Results:BMI-defined obesity (⩾30 kg m−2) was not associated with increased risk of mortality (HR=0.93; 95% confidence interval=0.80–1.08), whereas the overweight category (25–<30 kg m−2) was associated with a decreased risk (0.80; 0.70–0.91). In contrast, the HR for a high WC (men⩾102 cm, women⩾88 cm) was 1.17 (1.02–1.34) and a high WHR (men⩾1, women⩾0.85) was 1.34 (1.16–1.55). There was an increased risk of cardiovascular disease (CVD) mortality associated with BMI-defined obesity, a high WC and a high WHR categories; the HR estimates for these were 1.36 (1.05–1.77), 1.41 (1.11–1.79) and 1.44 (1.12–1.85), respectively. A low BMI (<18.5 kg m−2) was associated with elevated HR for all-cause mortality (2.66; 1.97–3.60), for chronic respiratory disease mortality (3.17; 1.39–7.21) and for acute respiratory disease mortality (11.68; 5.01–27.21). This pattern was repeated for WC but not for WHR.Conclusions:It might be prudent not to use BMI as the sole measure to summarize body size. The alternatives WC and WHR may more clearly define the health risks associated with excess body fat accumulation. The lack of association between elevated BMI and mortality may reflect the secular decline in CVD mortality.

Metabolic syndrome (MetS) criteria include central obesity assessed by waist circumference (WC), which may be confounded by body weight. We evaluated whether substituting the weight-adjusted waist index (WWI) for WC improves prediction of long-term cardiovascular disease (CVD) events and mortality. To compare the prognostic performance of a WWI-based MetS definition versus the classic WC-based MetS definition for predicting CVD events and mortality, utilizing 17 years of follow-up data from the Isfahan Cohort Study (ICS). Of the 6,504 participants aged ≥ 35 years without prior CVD at baseline, 919 (14.1%) were lost to follow-up over 17 years. The remaining 5,585 participants were included in the final analysis. The classic and modified MetS definitions were compared using Cox regression analysis, Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, and risk reclassification by net reclassification improvement (NRI) for CVD events, CVD mortality, and all-cause mortality. The modified WWI-based MetS reclassified approximately 9.2% of participants and significantly improved risk classification for incident CVD events (NRI = + 0.41, p < 0.0001). In crude analyses, the modified MetS was associated with higher risk of incident CVD events compared to the classic definition. After full adjustment, associations attenuated but remained significant for CVD events (modified HR 1.19, 95% CI: 1.01-1.41; classic HR 1.25, 95% CI: 1.06-1.47), whereas associations with CVD and all-cause mortality lost significance. Kaplan-Meier analyses confirmed significant differences in survival by MetS status for both definitions. The modified definition demonstrated modest improvements in sensitivity, specificity, accuracy, and area under the ROC curve (AUC) (CVD events: 0.62 vs. 0.60; CVD mortality: 0.63 vs. 0.59; all-cause mortality: 0.59 vs. 0.55) for all outcomes compared to the classic definition. In this 17-year cohort, replacing WC with WWI in the MetS definition modestly improved prediction of cardiovascular events and mortality. Using WWI in MetS criteria may enhance risk stratification in clinical practice. Further studies are needed to validate these findings across diverse populations.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Sciene Center of Poland The inverse association between social isolation or low social support and cardiovascular disease (CVD) is known but the evidence comes mainly form countries of stable high socio-economic development while research from populations of different social backgrounds remains scarce. Societies of Central and Eastern Europe which underwent profound socio-economic changes followed by the decrease in CVD mortality provide an interesting setting for a study of social determinants of health. The aim of the study was to assess the relationship between social networks and CVD incidence and mortality in Polish urban population. Additionally predictive performance of social networks index was compared with marital status alone. A cohort study with 10-year follow-up was conducted. A random sample of 10,728 residents of our city, aged 45 to 69 was examined. Social networks were assessed at baseline using questions on marital status, participation in groups and organizations as well as the number of friends and relatives with whom participants maintained contact. Points in individual categories were summed up and an index ranging from 0-4 was obtained where higher values meant bigger social networks. Information on new CVD cases was obtained from questionnaires in subsequent phases of the study and confirmed by the review of clinical records. Data on deaths and causes was obtained from the residents’ registry, Central Statistical Office, and participants’ families. The effect of social networks index as well as marital status on the risk of CVD was assessed using Cox proportional hazard models. The observation for incidence included 3,289 men and 3,673 women, respectively (384 and 175 new CVD cases). For CVD mortality 3,595 men and 3,939 women with 156 and 95 CVD deaths were included, respectively. In fully adjusted models no significant associations between social network index and CVD incidence were found. However, marital status was a significant predictor of CVD incidence in men; compared to single or widowed men those married or cohabiting had lower risk of CVD event by 33% (HR=0.67 95%CI=0.49-0.91). Protective effect of bigger social networks against CVD mortality with dose-response effect was observed in men only. Compared to men with the lowest social network index, any increase in the index was related with reduced risk of CVD mortality up to 86% in men with the highest social networks index (HR=0.14 95%CI=0.03-0.62). Lower risk of CVD death was also observed in married or cohabiting men compared to single or widowed participants (HR=0.40 95%CI=0.26-0.61). No significant differences in risk prediction was found between social index and marital status alone. In conclusion, maintaining social networks in middle-aged and older men from the urban population is protective against CVD mortality. However, social network index including information on social participation was not a better predictor of CVD risk than information on marital status alone.

Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study

Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega-3 PUFA and plant oils in omega-6 PUFA. Evidence suggests that increasing PUFA-rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. To assess effects of increasing total PUFA intake on cardiovascular disease and all-cause mortality, lipids and adiposity in adults. We searched CENTRAL, MEDLINE and Embase to April 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews. We included randomised controlled trials (RCTs) comparing higher with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all-cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials for further data. Meta-analyses used random-effects analysis, sensitivity analyses included fixed-effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence. We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA.Increasing PUFA intake probably has little or no effect on all-cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate-quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) andstroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low-quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality.Increasing PUFA intake probably slightly decreases triglycerides (by 15%, MD -0.12 mmol/L, 95% CI -0.20 to -0.04, 20 trials, 3905 participants), but has little or no effect on total cholesterol (mean difference (MD) -0.12 mmol/L, 95% CI -0.23 to -0.02, 26 trials, 8072 participants), high-density lipoprotein (HDL) (MD -0.01 mmol/L, 95% CI -0.02 to 0.01, 18 trials, 4674 participants) or low-density lipoprotein (LDL) (MD -0.01 mmol/L, 95% CI -0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably has little or no effect on adiposity (body weight MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants).Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via TG reduction.

Fruit, vegetable, and legume intake, and cardiovascular disease and deaths in 18 countries (PURE): a prospective cohort study

Systemic arterial hypertension affects 72 million US adults and an additional hundreds of millions of persons worldwide.1,2 Most of these are candidates for pharmacological treatment to reduce risk of cardiovascular disease (CVD) events, based primarily on a very large body of epidemiological and intervention research in humans. Because of this high prevalence and the cardiovascular consequences of untreated or inadequately treated hypertension, the selection of drugs for initial and continuing, long-term treatment has large public health and economic implications. Fortunately, such decisions and the expert recommendations that seek to guide them can call on evidence from 4 decades of randomized multicenter clinical trials evaluating effects of treatment on clinical CVD. We summarize that evidence in this article, in approximate chronological order, and we comment on the related treatment guidelines. We close with some of the major clinical questions yet to be resolved. Response by Messerli et al p 2705 Before the current era beginning in the early 1990s of emphasis on positive-control trials, which directly compare different drug regimens, there were 3 decades of trials that compared an active regimen with placebo or, in a few cases, “usual care.” For most of this period, the mainstay of treatment was generally a thiazide-type diuretic (hereinafter called thiazides) or, to a lesser extent, a β-adrenergic blocker (termed β-blockers). With few exceptions, these trials, especially those with high statistical power and thiazide-based regimens, showed benefit for CVD outcomes.3–8 This evidence, which provided a basis for recommending thiazides or β-blockers as first-step drugs in most editions of US guidelines through 1997,9 needs to continue to be given due weight in practice and practice guidelines. The largest and most consistent benefits from the earlier trials were for stroke and (where reported) heart failure. Benefits for coronary heart disease (CHD) were less clear, …

ImportanceThe US Preventive Services Task Force (USPSTF) is updating its 2016 recommendation on the use of aspirin for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC).ObjectiveTo provide updated model-based estimates of the net balance in benefits and harms from routine use of low-dose aspirin for primary prevention.Design, Setting, and ParticipantsMicrosimulation modeling was used to estimate long-term benefits and harms for hypothetical US cohorts of men and women aged 40 to 79 years with up to 20% 10-year risk for an atherosclerotic CVD event and without prior history of CVD or elevated bleeding risks.ExposuresLow-dose (≤100 mg/d) aspirin for lifetime use, unless contraindicated by a bleeding event, and with stopping ages in 5-year intervals from age 65 to 85 years.Main Outcomes and MeasuresPrimary outcomes were lifetime net benefits measured in quality-adjusted life-years (QALYs) and life-years. Benefits included reduced nonfatal myocardial infarction and ischemic stroke. Harms included increased nonfatal major gastrointestinal bleeding and intracranial hemorrhage. Reduced CRC incidence was considered in sensitivity analysis.ResultsEstimated lifetime net QALYs were positive for both men and women at 5% or greater 10-year CVD risk when starting between ages 40 and 59 years and at 10% or greater 10-year CVD risk when starting between ages 60 and 69 years. These estimates ranged from 2.3 (95% CI, −2.7 to 7.4) to 66.2 (95% CI, 58.2 to 74.1) QALYs per 1000 persons. Lifetime net life-years were positive for men at 5% or greater and women at 10% or greater 10-year CVD risk starting aspirin at ages 40 to 49 years and for men at 7.5% or greater and women at 15% or greater 10-year CVD risk at ages 50 to 59 years. These estimates ranged from 0.4 (95% CI, −6.1 to 6.9) to 52.4 (95% CI, 43.9 to 60.9) life-years per 1000 persons. Lifetime net life-years were negative in most cases for persons starting aspirin between ages 60 and 79 years, as were lifetime net QALYs for persons aged 70 to 79 years. Stopping aspirin between ages 65 and 85 years generally showed little advantage compared with lifetime use. Sensitivity analyses showed lifetime net benefits may be higher if aspirin reduced CRC incidence or CVD mortality and lower if aspirin increased fatal major gastrointestinal bleeding or reduced quality of life with routine use.Conclusions and RelevanceThis microsimulation study suggested that several population groups may benefit from taking aspirin for the primary prevention of CVD, primarily in persons starting at younger ages with higher 10-year CVD risk.

Premature mortality refers to deaths that occur before the expected age of death in a given population. Years of life lost (YLL) is a standard parameter that is frequently used to quantify some component of an "avoidable" mortality burden. To identify the studies on premature cardiovascular disease (CVD) mortality and synthesise their findings on YLL based on the regional area, main CVD types, sex, and study time. We conducted a systematic review of published CVD mortality studies that reported YLL as an indicator for premature mortality measurement. A literature search for eligible studies was conducted in five electronic databases: PubMed, Scopus, Web of Science (WoS), and the Cochrane Central Register of Controlled Trials (CENTRAL). The Newcastle-Ottawa Scale was used to assess the quality of the included studies. The synthesis of YLL was grouped into years of potential life lost (YPLL) and standard expected years of life lost (SEYLL) using descriptive analysis. These subgroups were further divided into WHO (World Health Organization) regions, study time, CVD type, and sex to reduce the effect of heterogeneity between studies. Forty studies met the inclusion criteria for this review. Of these, 17 studies reported premature CVD mortality using YPLL, and the remaining 23 studies calculated SEYLL. The selected studies represent all WHO regions except for the Eastern Mediterranean. The overall median YPLL and SEYLL rates per 100,000 population were 594.2 and 1357.0, respectively. The YPLL rate and SEYLL rate demonstrated low levels in high-income countries, including Switzerland, Belgium, Spain, Slovenia, the USA, and South Korea, and a high rate in middle-income countries (including Brazil, India, South Africa, and Serbia). Over the past three decades (1990-2022), there has been a slight increase in the YPLL rate and the SEYLL rate for overall CVD and ischemic heart disease but a slight decrease in the SEYLL rate for cerebrovascular disease. The SEYLL rate for overall CVD demonstrated a notable increase in the Western Pacific region, while the European region has experienced a decline and the American region has nearly reached a plateau. In regard to sex, the male showed a higher median YPLL rate and median SEYLL rate than the female, where the rate in males substantially increased after three decades. Estimates from both the YPLL and SEYLL indicators indicate that premature CVD mortality continues to be a major burden for middle-income countries. The pattern of the YLL rate does not appear to have lessened over the past three decades, particularly for men. It is vitally necessary to develop and execute strategies and activities to lessen this mortality gap. PROSPERO CRD42021288415.

Epidemiological studies reported an inconsistent association between stage 1 hypertension (SBP 130-139 mmHg or DBP 80-89 mmHg) defined by the 2017 American College of Cardiology/American Heart Association hypertension guidelines and cardiovascular disease (CVD) events. In addition, the proportion of CVD events that could be prevented with effective control of stage 1 hypertension is unknown. To assess the association between stage 1 hypertension and CVD events and estimate the population etiologic fraction. PubMed, Embase, and Web of Science databases were searched from 1 January 2017 to 22 September 2019. Normal BP was considered SBP less than 120 mmHg and DBP less than 80 mmHg. Hazard ratios and 95% confidence intervals (95% CIs) were pooled by using a random-effects model. We included 11 articles (16 studies including 3 212 447 participants and 65 945 events) in the analysis. Risk of CVD events was increased with stage 1 hypertension versus normal BP (hazard ratio 1.38, 95% CI 1.28-1.49). On subgroup analyses, stage 1 hypertension was associated with coronary heart disease (CHD) (hazard ratio 1.30, 95% CI 1.20-1.41), stroke (1.39, 1.27-1.52), CVD morbidity (1.42, 1.32-1.53), and CVD mortality (1.34, 1.05-1.71). The population etiologic fraction for the association of CVD events, CHD, stroke, CVD morbidity, and CVD mortality with stage 1 hypertension was 12.90, 10.48, 12.71, 14.03, and 11.69%, respectively. Stage 1 hypertension is associated with CVD events, CVD morbidity, CVD mortality, CHD, and stroke. Effective control of stage 1 hypertension could prevent more than 10% of CVD events.

Nut consumption and risk of cardiovascular disease events and all-cause mortality: A systematic review and dose-response meta-analysis of prospective cohort studies.

Disclosure: B.B. Yeap: None. R.J. Marriott: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. K. Murray: None. Studies examining associations of circulating sex steroids with mortality risk in men show inconsistent results for testosterone (T), with limited data for dihydrotestosterone (DHT) and estradiol (E2). We aimed to clarify associations of sex steroids, sex hormone-binding globulin (SHBG) and luteinising hormone (LH) with risks of all-cause and cardiovascular disease (CVD) mortality and incident CVD events in men, by conducting individual participant data (IPD) meta-analyses of prospective cohort studies with sex steroids measured using mass spectrometry. The Androgens In Men Study protocol was registered (PROSPERO: CRD42019139668) and published (BMJ Open 2020;10:e034777). A systematic review (completed Dec 2019) identified relevant studies (BMJ Open 2021;11:e048013). IPD were requested. Cox proportional hazards analyses related total T, SHBG, LH, DHT and E2 concentrations to risk of all-cause mortality and CVD deaths, and risk of incident CVD events. Models were adjusted for age and other sociodemographic factors, lifestyle factors, medical conditions and medications. Summary curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (24,596 men), with median baseline age 49-76 years and 4-20 years follow-up among studies. Associations of T with all-cause and CVD mortality risk were non-linear. Risk of all-cause mortality increased for men with baseline T concentrations &amp;lt;8.7 nmol/L, and risk of CVD death increased for men with baseline T &amp;lt;5.3 nmol/L. Lower SHBG concentrations were associated with lower risk of all-cause mortality (median Quintile [Q]1 vs Q5 [Q1:Q5], 20.6 vs 68.3 nmol/L; HR=0.85, CI=0.77-0.95), and CVD death (HR=0.81, CI 0.65-1.00). Men with LH &amp;gt;10 IU/L or E2 &amp;lt;5.1 pmol/L had higher all-cause mortality, with no association of LH or E2 with CVD deaths. Associations of DHT with all-cause and CVD mortality risk were non-linear. Men with lower baseline DHT concentrations had higher risk of all-cause mortality (median Q1:Q5, 0.69 vs 2.45 nmol/L; HR=1.19, CI=1.08-1.30) and CVD deaths (HR=1.29, CI=1.03-1.61), with risk increasing for DHT &amp;gt;2.45 nmol/L. Men with baseline DHT concentrations &amp;lt;0.59 nmol/L had increased risk of incident CVD events, no other hormones were associated with this outcome. Our results suggest greater all-cause and CVD mortality risk among men with very low baseline T, higher baseline SHBG, or either lower or very high baseline DHT concentrations. There was greater risk of CVD events among men with very low baseline DHT concentrations. Potential mechanisms by which SHBG and DHT might influence mortality risk in ageing men merit further investigation. Presentation: Thursday, June 15, 2023