Sibling rank and sibling number in relation to cardiovascular disease and mortality risk: a nationwide cohort study

BackgroundThe number and rank order of siblings could be of importance for risk of cardiovascular disease and mortality. Previous studies have used only fatal events for risk prediction. We, therefore, aimed to use also non-fatal coronary and cardiovascular events in fully adjusted models.MethodsFrom the Multiple-Generation Register in Sweden, data were used from 1.36 million men and 1.32 million women (born 1932–1960), aged 30–58 years at baseline and with follow-up from 1990 to 2015. Mean age at follow-up was 67 years (range 55–83 years). Fatal and non-fatal events were retrieved from national registers.ResultsCompared with men with no siblings, those with 1–2 siblings had a lower, and those with four or more siblings had a higher adjusted risk of cardiovascular events. Again, compared with men with no siblings, those with more than one sibling had a lower total mortality risk, and those with three or more siblings had an increased risk of coronary events.Correspondingly, compared with women with no siblings those women with three siblings or more had an increased risk of cardiovascular events, and those with two siblings or more had an increased risk of coronary events. Women with one sibling or more were at lower total mortality risk, following full adjustment.ConclusionBeing first born is associated with a favourable effect on non-fatal cardiovascular and coronary events for both men and women. The underlying biological mechanisms for this should be studied in a sociocultural context.

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Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population

Scientific Reports ◽

10.1038/s41598-021-93024-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xiaojing Chen ◽

Per-Olof Hansson ◽

Erik Thunström ◽

Zacharias Mandalenakis ◽

Kenneth Caidahl ◽

...

Keyword(s):

Cardiovascular Disease ◽

General Population ◽

Cardiovascular Events ◽

Population Sample ◽

Cox Regression Analysis ◽

Major Cardiovascular Events ◽

Increased Risk ◽

Qrs Duration ◽

Group 1

AbstractThe QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50–60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07–2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

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Primary prevention of cardiovascular disease in patients with systemic lupus erythematosus: case series and literature review

Lupus ◽

10.1177/0961203317722847 ◽

2017 ◽

Vol 26 (14) ◽

pp. 1463-1472 ◽

Cited By ~ 15

Author(s):

S Fasano ◽

D P Margiotta ◽

L Navarini ◽

L Pierro ◽

I Pantano ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cardiovascular Disease ◽

Cardiovascular Event ◽

Lupus Erythematosus ◽

Cardiovascular Events ◽

Hazard Ratio ◽

Systemic Lupus ◽

Increased Risk

Background Systemic lupus erythematosus is associated with an increased risk of cardiovascular disease. Low-dose aspirin, hydroxychloroquine and statins have been suggested to play a prophylactic role of cardiovascular events. This study is devoted to reviewing the literature on the topic and assessing the effects of these drugs in preventing a first cardiovascular event in a two-centre Italian series. Methods A PubMed search on cardiovascular prevention in systemic lupus erythematosus was performed. Moreover, systemic lupus erythematosus patients admitted to two centres from 2000–2015, who at admission had not experienced any cardiovascular event, were investigated. Aspirin, hydroxychloroquine and statin use, and the occurrence of any cardiovascular event, were recorded at each visit. Kaplan-Meier and Cox regression analyses were performed to evaluate the role of traditional, disease-related cardiovascular risk factors and of each of the three drugs in the occurrence of new cardiovascular events. Results The literature search produced conflicting results. Two hundred and ninety-one systemic lupus erythematosus patients were included in the study and followed for a median of eight years. During follow-up, 16 cardiovascular events occurred. At multivariate analysis, taking aspirin (hazard ratio: 0.24) and hydroxychloroquine for more than five years (hazard ratio: 0.27) reduced, while antiphospholipid antibody positivity (hazard ratio: 4.32) increased, the risk of a first cardiovascular event. No effect of statins emerged. Conclusion Our study confirms an additive role of aspirin and hydroxychloroquine in the primary prophylaxis of cardiovascular events in Italian patients with systemic lupus erythematosus. The lack of any detected effect in previous reports may depend on the design of studies and their short follow-up period.

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Associations of cereal grains intake with cardiovascular disease and mortality across 21 countries in Prospective Urban and Rural Epidemiology study: prospective cohort study

BMJ ◽

10.1136/bmj.m4948 ◽

2021 ◽

pp. m4948

Author(s):

Sumathi Swaminathan ◽

Mahshid Dehghan ◽

John Michael Raj ◽

Tinku Thomas ◽

Sumathy Rangarajan ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Cohort Study ◽

Cardiovascular Events ◽

Total Mortality ◽

Whole Grains ◽

Refined Grains ◽

White Rice ◽

Major Cardiovascular Events

Abstract Objective To evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study. Design Prospective cohort study. Setting PURE study in 21 countries. Participants 148 858 participants with median follow-up of 9.5 years. Exposures Country specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice. Main outcome measure Composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre. Results Analyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes. Conclusion High intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.

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Fruit, vegetable and bean intake and mortality from cardiovascular disease among Japanese men and women: the JACC Study

British Journal Of Nutrition ◽

10.1017/s0007114508143586 ◽

2009 ◽

Vol 102 (2) ◽

pp. 285-292 ◽

Cited By ~ 97

Author(s):

Junko Nagura ◽

Hiroyasu Iso ◽

Yoshiyuki Watanabe ◽

Koutatsu Maruyama ◽

Chigusa Date ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Cancer Risk ◽

Mortality Risk ◽

Vegetable Intake ◽

Total Mortality ◽

Fruit Intake ◽

Japanese Men ◽

Men And Women

To examine the association of plant-based food intakes with CVD and total mortality among Japanese. In the Japan Collaborative Cohort Study for Evaluation of Cancer Risk, 25 206 men and 34 279 women aged 40–79 years, whose fruit, vegetable and bean intakes were assessed by questionnaire at baseline in 1988–90, were followed for 13 years. Deaths from total stroke, stroke subtypes, CHD and total CVD, according to the International Classification for Diseases 10th Revision, were registered. During 756 054 person-years of follow-up, there were 559 deaths from total stroke, 258 from CHD, 1207 from total CVD and 4514 from total mortality for men, and for women, 494, 194, 1036 and 3092, respectively. Fruit intake was inversely associated with mortality from total stroke (the multivariable hazard ratio (HR (95 % CI)) in the highest v. lowest quartiles = 0·67 (0·55, 0·81)), total CVD (HR = 0·75 (0·66, 0·85)) and total mortality (HR = 0·86 (0·80, 0·92)). Vegetable intake was inversely associated with total CVD (HR = 0·88 (0·78, 0·99)). Bean intake was inversely associated with other CVD (HR = 0·79 (0·64, 0·98)), total CVD (HR = 0·84 (0·74, 0·95)) and total mortality (HR = 0·90 (0·84, 0·96)). Further adjustment for other plant-based foods did not alter the association of fruit intake with mortality from total stroke, total CVD and total mortality, but attenuated the associations of vegetables and beans with mortality risk. In conclusion, intakes of plant-based foods, particularly fruit intake, were associated with reduced mortality from CVD and all causes among Japanese men and women.

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Abstract 13852: Socioeconomic Status is Associated With Recurrent Cardiovascular Disease Events in People With Prevalent Cardiovascular Disease

Circulation ◽

10.1161/circ.142.suppl_3.13852 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lena Mathews ◽

Ning Ding ◽

Yejin Mok ◽

Matthew S Loop ◽

Amira Collison ◽

...

Keyword(s):

Cardiovascular Disease ◽

Socioeconomic Status ◽

Low Socioeconomic Status ◽

Total Mortality ◽

Income Group ◽

High Risk Group ◽

Area Deprivation ◽

Established Risk Factor ◽

Increased Risk

Introduction: While low socioeconomic status (SES) is an established risk factor for incident cardiovascular disease (CVD), there is scarce data regarding the association between SES and recurrent CVD events. Hypothesis: SES measures are associated with recurrent CVD events and mortality among those with prevalent CVD. Methods: We examined 3,031 individuals in the ARIC Study who developed CVD (either myocardial infarction [MI], heart failure [HF] or stroke) from the baseline visit (1987-1989) through 2013 to allow 5 years follow-up for recurrent CVD. SES was defined using baseline measures of income, education and area deprivation index (ADI), modeled individually and combined in a cumulative SES score. We used adjusted Cox proportional hazard regression to evaluate the associations of SES with composite and individual outcomes of first recurrent CVD and mortality. Results: Median age was 69 years, 49% were female, 29% Black. Over a median follow up of 4.6 years, 2,033 participants (67%) had a recurrent CVD event, and 2,202 (73%) died. Relative to the highest income group, being in the lowest income group was associated with higher risk for recurrent CVD (HR 1.27; 95% CI: 1.07-1.51) and mortality (HR 1.32; 95% CI: 1.12-1.56) ( Table ). Similarly, less than high school education was associated with increased risk of recurrent CVD (HR 1.25; 95% CI: 1.04-1.51) and mortality (HR 1.21; 95% CI: 1.01-1.45). No significant outcome associations were seen for ADI. Low cumulative SES was associated with approximately 20% higher risk of recurrent CVD, total mortality and the composite of recurrent CVD and mortality. Similar patterns were seen for individual subtypes of CVD, with the strongest SES-mortality associations for MI and stroke. Conclusions: In the high-risk group of individuals with existing CVD, low SES was linked to greater likelihood of recurrent CVD events and death. SES should be a focus in the design of secondary prevention efforts to improve outcomes in CVD.

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Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials

Vascular Medicine ◽

10.1191/1358863x05vm602oa ◽

2005 ◽

Vol 10 (2_suppl) ◽

pp. S19-S25 ◽

Cited By ~ 22

Author(s):

Rainer H Böger

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Clinical Trials ◽

Cardiovascular Risk ◽

Cardiovascular Events ◽

Asymmetric Dimethylarginine ◽

Total Mortality ◽

No Production ◽

Increased Risk ◽

Diverse Patient Populations

Evidence has accumulated that asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; it also causes local vasoconstriction when infused intra-arterially. ADMA is increased in the plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, chronic heart failure, and other clinical conditions. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation or reduced NO metabolite levels. In several prospective and cross-sectional studies, ADMA has evolved as a marker of cardiovascular risk. Moreover, prospective clinical studies have suggested that it may play a role as a novel cardiovascular risk factor. Zoccali and coworkers were the first to show that elevated ADMA is associated with a three-fold increased risk of future severe cardiovascular events and mortality in patients undergoing hemodialysis. Valkonen and coworkers demonstrated in a nested case-control study that elevated ADMA was associated with a four-fold increased risk for acute coronary events in clinically healthy, nonsmoking men. In patients with stable angina pectoris, preinterventional ADMA indicates the risk of developing restenosis or severe clinical events after coronary intervention. Furthermore, in humans with no underlying cardiovascular disease who are undergoing intensive care unit treatment, ADMA is a marker of the mortality risk. A number of additional prospective clinical trials are currently under way in diverse patient populations, among them individuals with congestive heart failure, cardiac transplantation patients, and patients with pulmonary hypertension. In summary, an increasing number of prospective clinical trials have shown that the association between elevated ADMA levels and major cardiovascular events and total mortality is robust and extends to diverse patient populations. However, we need to define more clearly in the future who will profit from ADMA determination, in order to use this novel risk marker as a more specific diagnostic tool.

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P1519IL6 trans-signalling affects risk of cardiovascular events pre-eminently in men

European Heart Journal ◽

10.1093/eurheartj/ehz748.0281 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

L Ziegler ◽

P Frumento ◽

H Wallen ◽

U De Faire ◽

B Gigante

Keyword(s):

Cardiovascular Disease ◽

Quantile Regression ◽

Cardiovascular Events ◽

Ternary Complex ◽

Binary Complex ◽

Men And Women ◽

Censored Quantile Regression ◽

Increased Risk ◽

Significant Difference

Abstract Background Interleukin 6 (IL6) is a known cardiovascular risk marker. The pro-atherogenic effects of IL6 are mediated by the IL6 trans-signalling pathway via a binary complex of IL6 and the soluble IL6 receptor (IL6:sIL6R). The binary complex is however neutralised by the natural inhibitor, sgp130 when forming the ternary complex (IL6:sIL6R:sgp130). To assess the risk of cardiovascular events (CVE) with IL6 trans-signalling, a ratio between the active binary complex and the neutralised ternary complex was calculated. We recently demonstrated that high levels of the binary/ternary complex ratio (b/t ratio > the median) representing an excess of the active binary complex, was independently associated with a 44% increased risk of future CVE in subjects free of prevalent cardiovascular disease. Purpose In this study we aimed to analyse the risk of CVE and time to event associated with the b/t ratio in men and women separately. Methods In a cohort of 60 year old men and women from Stockholm, the molar concentrations of the binary and ternary IL6 complex were estimated at baseline. Subjects free of prevalent cardiovascular disease were followed through national registers to assess future CVE (myocardial infarction, hospitalised angina pectoris and ischemic stroke). During a 16 year follow-up, 525 first time CVEs were registered. The risk for CVE and time to CVE was calculated for men and women, separately. To evaluate the risk associated with IL6 trans-signalling, the b/t ratio dichotomised at the median was modelled in a Cox regression model and risk was expressed as hazard ratios (HR) with 95% confidence intervals (CI). In addition, analysis was performed using censored quantile regression that allows measuring the effect of covariates on different quantiles of the time to CVE. Results Approximately half of the population were men and 64% of the CVE occurred in men. The risk of CVE during follow-up was significantly higher in men with b/t ratio > median (HR 1.70; 95% CI 1.35–2.15), while no significant difference was found in women (HR 1.12; 95% CI 0.84–1.50). Consistently, quantile regression showed that, men with a b/t ratio > median suffered their CVEs at an earlier time point. The time at which 15% of the male population was observed to have experienced CVE was 5.6 years shorter (95% CI: 4.0–7.2) in the high b/t ratio group. In women there was no significant difference in time to CVE. Conclusion The risk of CVE and early events associated with IL6 trans-signalling estimated by a b/t ratio >median is significantly increased in men. Acknowledgement/Funding The Stockholm County Council ALF project, Strategic research in Epidemiology

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Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials

Vascular Medicine ◽

10.1177/1358836x0501000104 ◽

2005 ◽

Vol 10 (1_suppl) ◽

pp. S19-S25 ◽

Cited By ~ 40

Author(s):

Rainer H Böger

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Clinical Trials ◽

Cardiovascular Events ◽

Asymmetric Dimethylarginine ◽

Total Mortality ◽

No Production ◽

Intensive Care Unit Treatment ◽

Increased Risk ◽

Diverse Patient Populations

Evidence has accumulated that asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; it also causes local vasoconstriction when infused intra-arterially. ADMA is increased in the plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, chronic heart failure, and other clinical conditions. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation or reduced NO metabolite levels. In several prospective and cross-sectional studies, ADMA has evolved as a marker of cardio vascular risk. Moreover, prospective clinical studies have suggested that it may play a role as a novel cardiovascular risk factor. Zoccali and coworkers were the first to show that elevated ADMA is associated with a three-fold increased risk of future severe cardiovascular events and mortality in patients undergoing hemodialysis. Valkonen and coworkers demonstrated in a nested case-control study that elevated ADMA was associated with a four-fold increased risk for acute coronary events in clinically healthy, nonsmoking men. In patients with stable angina pectoris, pre- interventional ADMA indicates the risk of developing restenosis or severe clinical events after coronary intervention. Furthermore, in humans with no underlying cardiovascular disease who are undergoing intensive care unit treatment, ADMA is a marker of the mortality risk. A number of additional prospective clinical trials are currently under way in diverse patient populations, among them individuals with congestive heart failure, cardiac transplantation patients, and patients with pulmonary hypertension. In summary, an increasing number of prospective clinical trials have shown that the association between elevated ADMA levels and major cardiovascular events and total mortality is robust and extends to diverse patient populations. However, we need to define more clearly in the future who will profit from ADMA determination, in order to use this novel risk marker as a more specific diagnostic tool.

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Abstract 1245: The Mortality Rate from Cardiovascular Disease is more than Five Times Higher in Individuals with Diabetes Mellitus who have the Hp 2–2 Genotype as Compared to Individuals with Diabetes Mellitus who do not have the Hp 2–2 Genotype

Circulation ◽

10.1161/circ.118.suppl_18.s_1087-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Uzi Milman ◽

Shany Blum ◽

Chen Shapira ◽

Andrew Levy

Keyword(s):

Diabetes Mellitus ◽

Cardiovascular Disease ◽

Treatment Strategies ◽

Total Mortality ◽

Fold Increase ◽

High Risk Population ◽

Risk Of Death ◽

Health Care Clinics ◽

Increased Risk

Objective: To determine if the Haptoglobin (Hp) genotype can predict the risk of death from cardiovascular disease in individuals with Diabetes Mellitus (DM) in a prospective community based longitudinal study. Background: The Hp gene is polymorphic in man with two classes of alleles denoted 1 and 2. Retrospective analysis of 5 longitudinal studies has demonstrated that the Hp genotype is a major determinant of the risk of incident CVD in DM individuals. Specifically, individuals with the Hp 2–2 genotype and DM were found to have a 2–5 fold increased risk of CVD as compared to Hp 1–1 or Hp 2–1 DM individuals. Method: 2241 individuals with DM ≥55 years of age from 47 primary health care clinics were Hp genotyped and followed prospectively for three years for incident myocardial infarction, stroke and death (all cause and cardiovascular). All aspects of the medical care of individuals in the cohort were left to the discretion of the patient’s physician. Results: The cohort consisted of 708 individuals with the Hp 2–2 genotype and 1533 individuals with the Hp 1–1 or 2–1 genotype. At baseline there were no significant differences between individuals with and without the Hp 2–2 genotype in their DM characteristics (HbA1c, duration) or in the prevalence of cardiovascular disease (25% in both groups). During the nearly 3 year period of follow up total mortality was increased in individuals with the Hp 2–2 genotype (2.5% vs 1.8%, HR 0.68, CI 0.35–1.25, p=0.2 by log rank). These differences in overall mortality were the result of a greater than 5 fold increase in CV death in Hp 2–2 individuals (1.1% vs 0.2%, HR 0.15, CI 0.038 – 0.44, p=0.001 by log rank). The incidence of non fatal MI was increased by over 50% in the Hp 2–2 group (3.9% vs. 2.5%, p=0.068). These differences were unaffected by adjustment for DM characteristics and conventional cardiovascular risk factors. Conclusions. DM individuals with the Hp 2–2 genotype are at a dramatically increased risk of death due to cardiovascular disease. Pharmacogenomic treatment strategies targeted to this high risk population may provide considerable public health and economic benefit.

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Abstract 2453: Exercise Capacity is Inversely Associated with Mortality Risk in Pre-Hypertensive Men

Circulation ◽

10.1161/circ.118.suppl_18.s_728-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Andreas E Pittaras ◽

Jonathan Myers ◽

Puneet Narayan ◽

Athanasios Manolis ◽

Charles Faselis ◽

...

Keyword(s):

Exercise Capacity ◽

Mortality Risk ◽

Strong Association ◽

Hazard Ratio ◽

Peak Exercise ◽

Adjusted Risk ◽

Epidemiologic Evidence ◽

Increased Risk ◽

Lower Hazard

Introduction: Epidemiologic evidence supports an inverse and strong association between fitness status, and mortality in healthy individuals. Pre-hypertensive individuals are at increased risk for cardiovascular events compared to those with normal blood pressure. However, there is no information on the association between exercise capacity and mortality in pre-hypertensive individuals. Methods: We assessed the association between peak exercise capacity (METs) and all-cause mortality in pre-hypertensive men (n=4,735; age=56±12). We established four fitness categories based on the MET level achieved. Those who achieved <5 METs (n=674); 5–7 METs (n=1,170); 7.1 to 10 METs (1,784); and > 10 METs (n= n=1,107). There were 943 deaths over 22 years of follow-up (mean=8.0±5.5). Results : After adjusting for age, BMI, diabetes and dyslipidemia, exercise capacity was the strongest predictor of risk for mortality. The adjusted risk was reduced by 14% for every 1-MET increase in exercise capacity (Hazard Ratio= 0.86; CI: 0.84 – 0.88; p<0.001). When compared to those who achieved ≥5 METs, the mortality risk in those who achieved 5.1–7 METs was 25% lower (hazard ratio= 0.75; CI: 0.64 – 0.87; p<0.001); 60% lower for those who achieved 7.1–10 METs (hazard ratio= 0.40; CI: 0.33– 0.48; p<0.001), and 75% lower for those achieving >10 METs (Hazard Ratio= 0.25; CI: 0.19 – 0.33; p<0.001). Conclusions: The association between exercise capacity and mortality in pre-hypertensive individuals was strong, inverse and graded. The mortality risk was lowered by 14% for each 1-MET increase in exercise capacity. The overall reduction in mortality was 25% to 75% for those with an exercise capacity of >7 METs compared to those who achieved <5 METs.

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