Life's Essential 8 is associated with atherosclerotic cardiovascular disease but not venous thromboembolism in men: a prospective cohort study.

Background: Atherosclerotic cardiovascular disease (ASCVD) shares several risk factors with venous thromboembolism (VTE). The American Heart Association's Life's Simple 7 (LS7), which included seven health and behavioural factors for CVD prevention, has recently been upgraded to Life's Essential 8 (LE8) score. We aimed to examine the prospective association between LE8 and the risks of ASCVD and VTE in Finland.Methods: We utilized data based on 1899 men aged 42-61 years in the Kuopio Ischaemic Heart Disease (KIHD) prospective study. The LE8 score was generated from baselines measures of four health behaviours (physical activity, diet, nicotine exposure and sleep health) and four health factors (BMI, blood lipids, blood glucose and blood pressure). Each factor was scored from 0 to 100 and summed into a composite score. Participants were classified into quartiles (Q) based on the total LE8 score - Q1, ≤ 420; Q2, >420 to 485; Q3, >485 to 550; Q4, >550. Multivariable Cox regression models were utilized to determine the hazard ratios (HRs) along with the 95% confidence intervals (CI) for ASCVD and VTE.Results: After median follow-up durations of 24 and 25 years, 889 ASCVD and 127 VTE events were recorded, respectively. The risk of ASCVD was found to be 58% lower in men belonging to the highest LE8 quartile compared to those in the lowest quartile (HR:0.42; 95%CI: 0.34-0.51). There was no significant evidence of an association between LE8 and VTE risk (Q4 vs Q1, HR:1.02; 95%CI: 0.60-1.74).Conclusion: The risk of ASCVD was significantly lower in middle-aged and older Finnish men who had a high LE8 score, but there was no significant association with VTE. Further large-scale prospective studies conducted in women and other population groups are necessary to confirm these findings.

Key MessagesMen who had total Life's Essential 8 (LE8) score more than 550 had lower risk of atherosclerotic cardiovascular disease (ASCVD) compared with those with LE8 score ≤ 420.Increasing LE8 score by 50 can lower the risk of ASCVD, but not venous thromboembolism (VTE).The result supports continuous improvement in combined healthy behaviours and factors in LE8 composite score may lower future risk of heart disease or stroke.

Haemodynamic Gain Index Is Associated with Risk of Sudden Cardiac Death and Improves Risk Prediction: A Cohort Study.

INTRODUCTION: Haemodynamic gain index (HGI) is a novel haemodynamic parameter which can be obtained from cardiopulmonary exercise testing (CPX), but its association with sudden cardiac death (SCD) is not known. We aimed to assess the association of HGI with SCD risk in a long-term prospective cohort study. METHODS: HGI was calculated using heart rate and systolic blood pressure (SBP) responses measured in 1897 men aged 42­61 years during CPX from rest to peak exercise. Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Multivariable adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) were estimated for SCD. RESULTS: During a median follow-up of 28.7 years, 205 SCDs occurred. The risk of SCD decreased gradually with increasing HGI (p value for non-linearity = 0.63). A unit (bpm/mm Hg) higher HGI was associated with a decreased risk of SCD (HR: 0.84; 95% CI: 0.71-0.99), which was attenuated following adjustment for CRF. CRF was inversely associated with SCD, which remained after further adjustment for HGI (HR: 0.85; 95% CI: 0.77-0.94) per each unit higher CRF. Addition of HGI to a SCD risk prediction model containing established risk factors improved risk discrimination (C-index change = 0.0096; p = 0.017) and reclassification (net reclassification improvement [NRI] = 39.40%, p = 0.001). The corresponding values for CRF were (C-index change = 0.0178; p = 0.007) and (NRI = 43.79%, p = 0.001). CONCLUSION: Higher HGI during CPX is associated with a lower SCD risk, consistent with a dose-response relationship but dependent on CRF levels. Though HGI significantly improves the prediction and classification of SCD beyond common cardiovascular risk factors, CRF remains a stronger risk indicator and predictor of SCD compared to HGI.

Hemodynamic Gain Index Is Associated With Cardiovascular Mortality and Improves Risk Prediction: A PROSPECTIVE COHORT STUDY.

PURPOSE: The hemodynamic gain index (HGI) and cardiorespiratory fitness (CRF) are parameters assessed during cardiopulmonary exercise testing (CPX). The association between the HGI and cardiovascular disease (CVD) mortality is uncertain. We evaluated the association between the HGI and CVD mortality risk using a prospective study. METHODS: The HGI was calculated using heart rate (HR) and systolic blood pressure (SBP) measured in 1634 men aged 42-61 yr during CPX, using the formula: [(HR peak × SBP peak ) - (HR rest × SBP rest )]/(HR rest × SBP rest ). Cardiorespiratory fitness was directly measured using a respiratory gas exchange analyzer. RESULTS: During a median (IQR) follow-up of 28.7 (19.0, 31.4) yr, 439 CVD deaths occurred. The risk of CVD mortality decreased continuously with the increasing HGI ( P value for nonlinearity = .28). Each unit higher HGI (1.06 bpm/mm Hg) was associated with a decreased risk of CVD mortality (HR = 0.80: 95% CI, 0.71-0.89), which was attenuated after further adjustment for CRF (HR = 0.92: 95% CI, 0.81-1.04). Cardiorespiratory fitness was associated with CVD mortality and the association remained after adjustment for the HGI: (HR = 0.86: 95% CI, 0.80-0.92) per each unit (MET) higher CRF. Addition of the HGI to a CVD mortality risk prediction model improved risk discrimination (C-index change = 0.0285; P < .001) and reclassification (net reclassification improvement = 8.34%; P < .001). The corresponding values for CRF were a C-index change of 0.0413 ( P < .001) and a categorical net reclassification improvement of 14.74% ( P < .001). CONCLUSIONS: The higher HGI is inversely associated with CVD mortality in a graded fashion, but the association is partly dependent on CRF levels. The HGI improves the prediction and reclassification of the risk for CVD mortality.

Life's Essential 8 and the risk of cardiovascular disease death and all-cause mortality in Finnish men.

AIMS: The aim of the study was to examine the association between Life's Essential 8 (LE8) and the risk of cardiovascular and all-cause mortality. METHODS AND RESULTS: The LE8 was computed for 1662 men, aged 42-60 years, without pre-existing history of cardiovascular disease (CVD) at baseline in the Kuopio Ischaemic Heart Disease study. The LE8 factors include diet, physical activity, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and lipids. Each LE8 factor was scored between 0 and 100 points. The summation of all points generated the total LE8 score, which was categorized into quartiles ≤-420, >420-485, >485-550, and >550. Multivariable Cox regression models were used to estimate hazard ratios and 95% confidence intervals of LE8 scores for the outcomes. During a median follow-up of 30 years, 402 and 987 men died from CVD and any cause, respectively. The total LE8 score among participants ranged from 185 to 750. The higher the LE8 scores, the lower the risk of dying from CVD and all-cause. Following adjustment for age, alcohol consumption, and socio-economic status, every 50-unit increase in LE8 score was associated with 17% and 14% lower risk of CVD and all-cause deaths, respectively. Men within LE8 top quartile had 60% lower risk of CVD mortality when compared with those within the bottom quartile. CONCLUSION: Life's Essential 8 was strongly and inversely associated with the risk of CVD death and all-cause mortality among ageing men. Measures that promote optimal LE8 scores should be encouraged among the general population.

The association between the American Heart Association's Life's Essential 8 (LE8) and the risk of cardiovascular and all-cause mortality was examined using the Kuopio Ischaemic Heart Disease Risk Factor Study in Finland. The result supports continuous improvement in healthy behaviours and factors used in generating LE8 score, which may lower future risk of dying from heart disease. In this paper: • Men who had total LE8 score more than 550 had lower risk of dying from heart disease or any cause of death compared with those with LE8 score ≤ 420. • Increasing LE8 score by 50 can lower risk of dying from heart disease or any other cause.

Baseline and usual cardiorespiratory fitness and the risk of chronic kidney disease: A prospective study and meta-analysis of published observational cohort studies.

Chronic kidney disease (CKD) is a global public health burden but is largely preventable. Few studies have reported an association between high levels of cardiorespiratory fitness (CRF) and decreased risk of CKD. However, some relevant aspects of the association, such as the dose-response relationship and the long-term relevance of CRF levels to CKD, have yet to be addressed. We, therefore, aimed to quantify the nature and magnitude of the association between CRF and CKD in a cohort of 2099 men aged 42-61 years with normal kidney function at baseline. CRF was directly measured using a respiratory gas exchange analyzer during cardiopulmonary exercise testing. Hazard ratios (HRs) (95% CIs) were estimated for the incidence of CKD. Correction for within-person variability was made using data from repeat measurements of CRF taken 11 years after baseline. A total of 197 CKD events were recorded during a median follow-up of 25.8 years. The age-adjusted regression dilution ratio for CRF was 0.59 (95% CI: 0.53-0.65). The risk of CKD decreased in a graded fashion with increasing CRF. Comparing extreme tertiles of CRF, the HR (95% CI) for CKD was 0.67 (0.46-0.97) following adjustment for several established and emerging risk factors. The corresponding adjusted HR (95% CI) was 0.51 (0.27-0.96) following correction for within-person variability. In a meta-analysis of five population-based cohort studies (including the current study) comprising 32,447 participants and 4,043 CKD cases, the fully-adjusted risk ratios (95% CIs) for CKD comparing extreme tertiles of baseline and long-term CRF values were 0.58 (0.46-0.73) and 0.40 (0.27-0.59), respectively. Findings from a new prospective study and pooled analysis of previous studies plus the new study indicate that high CRF levels are strongly and independently associated with a reduced risk of CKD and consistent with a linear dose-response relationship. Using single baseline measurements of CRF to investigate the association between CRF and CKD risk could considerably underestimate the true association.

Cardiovascular health metrics and risk of heart failure in a Finnish population: a prospective cohort study.

AIMS: This study aimed to examine the association between cardiovascular health (CVH) metrics and the risk of heart failure (HF) in a Finnish population. METHODS AND RESULTS: We used the prospective population-based Kuopio Ischaemic Heart Disease cohort study comprising men aged 42-60 years at baseline (1984-89) and women aged 53-73 years at baseline (1998-2001). The CVH scores were computed from American Heart Association's CVH metrics for 2385 men and 825 women without a history of HF at baseline. The CVH scores, ranging from 0 to 14, were categorized into three: inadequate, average, and optimal groups. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for HF. During a median follow-up period of 27 years for men, and 18 years for women, 465 and 124 HF events were recorded, respectively. The mean ages for men and women were 53 and 63 years, respectively. One hundred and thirty-three men (5.6%) and 73 women (8.8%) had five or more ideal CVH metrics. Participants with optimal CVH scores had a 64% and 48% lower risk of HF when compared with those with inadequate CVH scores among men and women, respectively (HR, 95% CI: men = 0.36, 0.26-0.49, P < 0.01; women = 0.52, 0.31-0.89, P = 0.02). CONCLUSIONS: Optimal CVH metrics is associated with a lower risk of HF among an ageing Finnish population. Optimal CVH score should be targeted among the general population to reduce the risk of HF.

Serum copper and the risk of cardiovascular disease death in Finnish men.

BACKGROUND AND AIMS: Copper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories. METHODS AND RESULTS: This Finnish prospective study is based on 1911 men aged 42-60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m2, pre-obesity 25-29.9 kg/m2, and obesity >30 kg/m2. The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05-2.01), 1.69(1.25-2.27), and 1.68(1.23-2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27-5.78)). CONCLUSION: Elevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.

Objectively Assessed Cardiorespiratory Fitness and All-Cause Mortality Risk: An Updated Meta-analysis of 37 Cohort Studies Involving 2,258,029 Participants.

OBJECTIVE: To detail the magnitude and specificity of the association between cardiorespiratory fitness (CRF) and all-cause mortality risk. METHODS: Cohort studies with at least 1 year of follow-up were sought from inception until December 2021 in MEDLINE, Embase, Web of Science, and a manual search of relevant articles. Relative risks (RRs) with 95% CIs were pooled using random-effects models. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool. RESULTS: A total of 37 unique studies comprising of 2,258,029 participants with 108,613 all-cause mortality events were eligible. The pooled multivariable-adjusted RR for all-cause mortality comparing the top vs bottom tertiles of CRF levels was 0.55 (95% CI, 0.50 to 0.61). When CRF was expressed in metabolic equivalent task (MET) units, the corresponding pooled RR was 0.56 (95% CI, 0.50 to 0.62). For every 1-MET increase in CRF, the RR for all-cause mortality was 0.89 (95% CI, 0.86 to 0.92). Strength of the association did not differ by publication year, age, sex, follow-up duration, CRF assessment method, or risk of bias. CONCLUSION: Aggregate analysis of observational cohort studies confirms a strong inverse and independent association between CRF and all-cause mortality risk. The results suggest that guideline bodies should consider the inclusion of CRF in standard risk panels for mortality risk assessment.

Handgrip strength and risk of cognitive outcomes: new prospective study and meta-analysis of 16 observational cohort studies.

Handgrip strength (HGS), a measure of muscular strength, might be a risk indicator for cognitive functioning, but the evidence is not consistent. Using a new prospective study and meta-analysis of published observational cohort studies, we aimed to evaluate the prospective associations of HGS with poor cognitive outcomes including cognitive impairment, dementia and Alzheimer's disease (AD). Handgrip strength, measured using a Martin-Balloon-Vigorimeter, was assessed at baseline in a population-based sample of 852 men and women with good cognitive function in the Kuopio Ischemic Heart Disease cohort. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for cognitive outcomes. Relevant published studies were sought in MEDLINE, Embase and Web of Science from inception until October 2021 and pooled using random effects meta-analysis. During a median follow-up of 16.6 years, 229 dementia cases were recorded. Comparing extreme tertiles of HGS, the multivariable adjusted HR (95% CI) for dementia, AD and vascular dementia was 0.77 (0.55-1.07), 0.75 (0.52-1.10) and 0.49 (0.16-1.48), respectively. In a meta-analysis of 16 population-based prospective cohort studies (including the current study) comprising 180,920 participants, the pooled multivariable adjusted relative risks (95% CIs) comparing the top vs bottom thirds of HGS levels were as follows: 0.58 (0.52-0.65) for cognitive impairment; 0.37 (0.07-1.85) for cognitive decline; 0.73 (0.62-0.86) for dementia; 0.68 (0.53-0.87) for AD; and 0.48 (0.32-0.73) for vascular dementia. GRADE quality of evidence ranged from low to very low. Meta-analysis of aggregate prospective data suggests that HGS may be a risk indicator for poor cognitive outcomes such as cognitive impairment, dementia and AD. Systematic review registration: PROSPERO 2021: CRD42021237750.

Life's Simple 7 and the risk of stroke in Finnish men: A prospective cohort study.

BACKGROUND: Population-wide preventive measures constitute important approaches towards reducing stroke risk and its associated burden. We sought to examine the association between American Heart Association's (AHA) Life's Simple7 (LS7) score and the risk of stroke in men. METHODS: The study is based on the prospective population-based Kuopio Ischaemic Heart Disease cohort comprising men (42-60 years) without pre-existing history of stroke at baseline (1984-1989). LS7 was computed from AHA's cardiovascular health metrics for 2520 men and includes data on diet, physical activity, body mass index, smoking status, blood pressures, total cholesterol and blood glucose. Participants were classified into three LS7 groups based on the number of ideal metrics: low (0-2), medium (3-4) and high (5-7). Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of LS7 scores for total and ischaemic stroke. RESULTS: During a median follow-up of 26 years, 428 total and 362 ischaemic incident stroke events were recorded. The risk of both stroke outcomes decreased continuously with increasing LS7 scores across the range 2-6. Men with high LS7 had 48% (HR: 0.52; 95%CI: 0.32-0.86) lower risk of total stroke when compared with those with low LS7. The association was similar for the risk of ischaemic stroke, with 50% (HR: 0.50; 95%CI: 0.29-0.87) lower risk among men with high LS7 compared with those with low LS7. CONCLUSION: LS7 was strongly, inversely and linearly associated with risk of total and ischaemic strokes among a middle-aged male Finnish population.

Handgrip strength-A risk indicator for type 2 diabetes: Systematic review and meta-analysis of observational cohort studies.

AIMS: Evolving debate suggests that handgrip strength (HGS), a measure of muscular strength, might be associated with the risk of type 2 diabetes (T2D); however, the evidence is conflicting. Using a systematic review and meta-analysis of published observational cohort studies in general populations, we aimed to assess the association of HGS with the future risk of T2D. METHODS: Relevant studies were sought from inception until April 2020 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Transformed or extracted relative risks (RRs) with 95% confidence intervals (CIs) comparing the top vs bottom thirds of HGS levels were pooled using random effects meta-analysis. RESULTS: A total of 10 unique observational cohort studies comprising of 177 826 participants and >5167 T2D cases were eligible. The pooled multivariable RR (95% CI) for T2D comparing the top vs bottom thirds of HGS levels was 0.73 (0.63-0.84). This association was consistent across several relevant subgroups except for evidence of effect modification by sample size (P value for meta-regression <.001): evidence of an association in smaller studies (<250 events) 0.50 (0.40-0.63), with no significant association in bigger studies (≥250 events) 0.87 (0.73-1.05). There was no evidence of small study effects using formal tests such as funnel plots and Egger's regression symmetry test. CONCLUSION: Pooled analysis of observational cohort studies suggests that HGS may be a risk indicator for T2D in the general population. The role of utilizing HGS measurements in T2D prevention strategies warrants further investigation.

Ideal cardiovascular health and risk of acute myocardial infarction among Finnish men.

BACKGROUND AND AIMS: Acute myocardial infarction (AMI) is associated with high mortality globally and remains a public health burden. We sought to investigate the relation between the American Heart Association's cardiovascular health metrics (CVH) and the risk of AMI among middle-aged Finnish men. METHODS: We used the ongoing population-based Kuopio Ischaemic Heart Disease cohort study comprising men aged 40-62 years at baseline. The CVH metrics was computed among 2584 participants at baseline with health scores ranging from 0 to 7. This was categorized into three groups of CVH metrics as poor (0-2), intermediate (3-4) and ideal (≥5). Multivariate Cox regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) of CVH metrics for AMI. RESULTS: During a median follow-up period of 25.2 years, 513 cases of AMI were recorded. Only one participant was able to achieve all the seven ideal health metrics. The risk of AMI decreased continuously with the increasing number of CVH metrics across the range 2-7 (for non-linearity, p = 0.07). Men with ideal CVH metrics had a HR (95% CI) for AMI of 0.28 (CI 0.15-0.55, p < 0.001) compared to those with poor CVH metrics after adjustment for age, alcohol intake and socioeconomic status. The associations remained consistent following further adjustment for history of coronary heart disease and history of type 2 diabetes. CONCLUSIONS: Ideal CVH metrics was strongly and linearly associated with reduced risk of AMI among middle-aged Finnish men.

American heart association's cardiovascular health metrics and risk of cardiovascular disease mortality among a middle-aged male Scandinavian population.

Background: The burden of cardiovascular disease (CVD) prompted the American Heart Association to develop a cardiovascular health (CVH) metric as a measure to assess the cardiovascular status of the population. We aimed to assess the association between CVH scores and the risk of CVD mortality among a middle-aged Finnish population. Methods: We employed the prospective population-based Kuopio Ischemic Heart Disease cohort study comprising of middle-aged men (42-60 years). CVH scores were computed among 2607 participants at baseline and categorized as optimum (0-4), average (5-9), or inadequate (10-14) CVH. Multivariate cox regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) of CVH score for cardiovascular mortality. Results: During a median follow-up period of 25.8 years, 609 CVD mortality cases were recorded. The risk of CVD mortality increased gradually with increasing CVH score across the range 3-14 (p-value for non-linearity =.77). Men with optimum CVH score had HR (95% CI) for CVD mortality of 0.30 (CI 0.21 - 0.42, p < .0001) compared to those with inadequate CVH score after adjustment for conventional cardiovascular risk factors. Conclusions: CVH score was strongly and continuously associated with the risk of CVD mortality among middle-aged Finnish population and this was independent of other conventional risk factors. Key messages Achieving optimum cardiovascular health score reduces the risk of cardiovascular mortality. Adopting the American Heart Association's cardiovascular health metrics is a welcome approach for public health awareness and monitoring of cardiovascular health among Scandinavian population.

Marriage Dissatisfaction and the Risk of Sudden Cardiac Death Among Men.

Conflicts in marriage have been associated with potential risk of cardiovascular disease; however, there is lack of prospective evidence on the association between marriage satisfaction and sudden cardiac death (SCD). We aimed to assess the association between perceived level of marriage satisfaction and risk of SCD. This study employed the Kuopio Ischemic Heart Disease study, an ongoing prospective population-based study in Finland. Perceived level of marriage satisfaction was assessed in 2,262 men using a well-structured self-administered questionnaire. Multivariable adjusted Cox regression models were used to estimate hazard ratios (95% confidence interval [CI]) for SCD. During a median follow-up period of 25.9 years, 239 SCDs were recorded. The mean age of participants was 53 (SD 5.2) years. On adjustment for several conventional cardiovascular risk factors, hazard ratio (95% CI) of SCD was 1.90 (CI 1.09 to 3.32; p = 0.02) for men who were dissatisfied with their marriage, compared with men who were satisfied with their marriage. The association remained consistent on further adjustment for preexisting coronary heart disease, socioeconomic status, and years of education 1.86 (CI 1.07 to 3.25; p = 0.03). In conclusion, dissatisfied marriage is associated with an increased risk of SCD among middle-aged Caucasian men, independent of conventional cardiovascular risk factors.