scholarly journals Very High Coronary Artery Calcium (≥1000) and Association With Cardiovascular Disease Events, Non–Cardiovascular Disease Outcomes, and Mortality

Circulation ◽  
2021 ◽  
Vol 143 (16) ◽  
pp. 1571-1583
Author(s):  
Allison W. Peng ◽  
Zeina A. Dardari ◽  
Roger S. Blumenthal ◽  
Omar Dzaye ◽  
Olufunmilayo H. Obisesan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Secondary Prevention ◽  
Major Adverse Cardiovascular Event ◽  
Adverse Cardiovascular Event ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Event Rates ◽  
Very High

Background: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. Methods: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Results: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm 2 ), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63–6.11), 7.57- (5.50–10.42), 4.86-(3.32–7.11), and 1.94-fold (1.57–2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25–2.16), 1.66- (1.22–2.25), 1.51- (1.03–2.23), and 1.34-fold (1.05–1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57–2.41) and 1.43-fold (1.12–1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. Conclusions: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

scholarly journals Association of Rosacea With Cardiovascular Disease: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Daein Choi ◽  
Sungjun Choi ◽  
Seulggie Choi ◽  
Sang Min Park ◽  
Hyun‐Sun Yoon
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Cohort Study ◽  
Heart Disease ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Cox Regression ◽  
Hazard Ratios ◽  
Increased Risk

Background There is emerging evidence that rosacea, a chronic cutaneous inflammatory disease, is associated with various systemic diseases. However, its association with cardiovascular disease (CVD) remains controversial. We aimed to investigate whether patients with rosacea are at increased risk of developing CVD. Methods and Results This retrospective cohort study from the Korean National Health Insurance Service‐Health Screening Cohort included patients with newly diagnosed rosacea (n=2681) and age‐, sex‐, and index year–matched reference populations without rosacea (n=26 810) between 2003 and 2014. The primary outcome was subsequent CVD including coronary heart disease and stroke. Multivariable Cox regression analyses were used to evaluate adjusted hazard ratios for subsequent CVD adjusted for major risk factors of CVD. Compared with the reference population (13 410 women; mean [SD] age, 57.7 [9.2] years), patients with rosacea (1341 women; mean [SD] age, 57.7 [9.2] years) displayed an increased risk for CVD (adjusted hazard ratios, 1.20; 95% CI, 1.03–1.40) and coronary heart disease (adjusted hazard ratios, 1.29; 95% CI, 1.05–1.60). The risk for stroke was not significantly elevated (adjusted hazard ratios, 1.12; 95% CI, 0.91–1.37). Conclusions This study suggests that patients with rosacea are more likely to develop subsequent CVD. Proper education for patients with rosacea to manage other modifiable risk factors of CVD along with rosacea is needed.

scholarly journals Association between cholesterol efflux capacity and peripheral artery disease in coronary heart disease patients with and without type 2 diabetes: from the CORDIOPREV study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elena M. Yubero-Serrano ◽  
Juan F. Alcalá-Diaz ◽  
Francisco M. Gutierrez-Mariscal ◽  
Antonio P. Arenas-de Larriva ◽  
Patricia J. Peña-Orihuela ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Secondary Prevention ◽  
Peripheral Artery Disease ◽  
Cholesterol Efflux ◽  
Newly Diagnosed ◽  
Peripheral Artery ◽  
Cholesterol Efflux Capacity ◽  
Increased Risk ◽  
Artery Disease

Abstract Background Peripheral artery disease (PAD) is recognized as a significant predictor of mortality and adverse cardiovascular outcomes in patients with coronary heart disease (CHD). In fact, coexisting PAD and CHD is strongly associated with a greater coronary event recurrence compared with either one of them alone. High-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) is found to be inversely associated with an increased risk of incident CHD. However, this association is not established in patients with PAD in the context of secondary prevention. In this sense, our main aim was to evaluate the association between CEC and PAD in patients with CHD and whether the concurrent presence of PAD and T2DM influences this association. Methods CHD patients (n = 1002) from the CORDIOPREV study were classified according to the presence or absence of PAD (ankle-brachial index, ABI ≤ 0.9 and ABI > 0.9 and < 1.4, respectively) and T2DM status. CEC was quantified by incubation of cholesterol-loaded THP-1 cells with the participants' apoB-depleted plasma was performed. Results The presence of PAD determined low CEC in non-T2DM and newly-diagnosed T2DM patients. Coexisting PAD and newly-diagnosed T2DM provided and additive effect providing an impaired CEC compared to non-T2DM patients with PAD. In established T2DM patients, the presence of PAD did not determine differences in CEC, compared to those without PAD, which may be restored by glucose-lowering treatment. Conclusions Our findings suggest an inverse relationship between CEC and PAD in CHD patients. These results support the importance of identifying underlying mechanisms of PAD, in the context of secondary prevention, that provide potential therapeutic targets, that is the case of CEC, and establishing strategies to prevent or reduce the high risk of cardiovascular events of these patients. Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00924937. Unique Identifier: NCT00924937

Abstract P253: Proton Pump Inhibitor Use is Positively Associated with Incidence of Cardiovascular Disease

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Elizabeth J Bell ◽  
Jennifer L St. Sauver ◽  
Veronique L Roger ◽  
Nicholas B Larson ◽  
Hongfang Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Language Processing ◽  
Proton Pump ◽  
Hazard Ratio ◽  
Time Varying ◽  
Increased Risk ◽  
The Impact

Introduction: Proton pump inhibitors (PPIs) are used by an estimated 29 million Americans. PPIs increase the levels of asymmetrical dimethylarginine, a known risk factor for cardiovascular disease (CVD). Data from a select population of patients with CVD suggest that PPI use is associated with an increased risk of stroke, heart failure, and coronary heart disease. The impact of PPI use on incident CVD is largely unknown in the general population. Hypothesis: We hypothesized that PPI users have a higher risk of incident total CVD, coronary heart disease, stroke, and heart failure compared to nonusers. To demonstrate specificity of association, we additionally hypothesized that there is not an association between use of H 2 -blockers - another commonly used class of medications with similar indications as PPIs - and CVD. Methods: We used the Rochester Epidemiology Project’s medical records-linkage system to identify all residents of Olmsted County, MN on our baseline date of January 1, 2004 (N=140217). We excluded persons who did not grant permission for their records to be used for research, were <18 years old, had a history of CVD, had missing data for any variable included in our model, or had evidence of PPI use within the previous year.We followed our final cohort (N=58175) for up to 12 years. The administrative censoring date for CVD was 1/20/2014, for coronary heart disease was 8/3/2016, for stroke was 9/9/2016, and for heart failure was 1/20/2014. Time-varying PPI ever-use was ascertained using 1) natural language processing to capture unstructured text from the electronic health record, and 2) outpatient prescriptions. An incident CVD event was defined as the first occurrence of 1) validated heart failure, 2) validated coronary heart disease, or 3) stroke, defined using diagnostic codes only. As a secondary analysis, we calculated the association between time-varying H 2 -blocker ever-use and CVD among persons not using H 2 -blockers at baseline. Results: After adjustment for age, sex, race, education, hypertension, hyperlipidemia, diabetes, and body-mass-index, PPI use was associated with an approximately 50% higher risk of CVD (hazard ratio [95% CI]: 1.51 [1.37-1.67]; 2187 CVD events), stroke (hazard ratio [95% CI]: 1.49 [1.35-1.65]; 1928 stroke events), and heart failure (hazard ratio [95% CI]: 1.56 [1.23-1.97]; 353 heart failure events) compared to nonusers. Users of PPIs had a 35% greater risk of coronary heart disease than nonusers (95% CI: 1.13-1.61; 626 coronary heart disease events). Use of H 2 -blockers was also associated with a higher risk of CVD (adjusted hazard ratio [95% CI]: 1.23 [1.08-1.41]; 2331 CVD events). Conclusions: PPI use is associated with a higher risk of CVD, coronary heart disease, stroke and heart failure. Use of a drug with no known cardiac toxicity - H 2 -blockers - was also associated with a greater risk of CVD, warranting further study.

scholarly journals Osteopontin in Vascular Disease

2019 ◽  
Vol 39 (4) ◽  
pp. 613-622 ◽  
Author(s):  
Zoe Shin Yee Lok ◽  
Alicia N. Lyle
Keyword(s):  
Cardiovascular Disease ◽  
Vascular Disease ◽  
Strong Predictor ◽  
Healing Process ◽  
Major Adverse Cardiovascular Event ◽  
Adverse Cardiovascular Event ◽  
Acute Response ◽  
Increased Risk ◽  
Traditional Risk Factors

Inflammatory cytokines are necessary for an acute response to injury and the progressive healing process. However, when this acute response does not resolve and becomes chronic, the same proteins that once promoted healing then contribute to chronic inflammatory pathologies, such as atherosclerosis. OPN (Osteopontin) is a secreted matricellular cytokine that signals through integrin and CD44 receptors, is highly upregulated in acute and chronic inflammatory settings, and has been implicated in physiological and pathophysiologic processes. Evidence from the literature suggests that OPN may fit within the Goldilocks paradigm with respect to cardiovascular disease, where acute increases are protective, attenuate vascular calcification, and promote postischemic neovascularization. In contrast, chronic increases in OPN are clinically associated with an increased risk for a major adverse cardiovascular event, and OPN expression is a strong predictor of cardiovascular disease independent of traditional risk factors. With the recent finding that humans express multiple OPN isoforms as the result of alternative splicing and that these isoforms have distinct biologic functions, future studies are required to determine what OPN isoform(s) are expressed in the setting of vascular disease and what role each of these isoforms plays in vascular disease progression. This review aims to discuss our current understanding of the role(s) of OPN in vascular disease pathologies using evidence from in vitro, animal, and clinical studies. Where possible, we discuss what is known about OPN isoform expression and our understanding of OPN isoform contributions to cardiovascular disease pathologies.

scholarly journals Comparison of Cystatin C and Creatinine as Predictors of Cardiovascular Events in a Community-Based Elderly Population

2010 ◽  
Vol 56 (5) ◽  
pp. 799-804 ◽  
Author(s):  
John Beilby ◽  
Mark L Divitini ◽  
Matthew W Knuiman ◽  
Enrico Rossi ◽  
Joseph Hung
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Renal Function ◽  
Heart Disease ◽  
Creatinine Clearance ◽  
Cystatin C ◽  
Cardiovascular Events ◽  
Community Based ◽  
Hazard Ratios

Abstract Background: Reduced renal function is an established risk factor for cardiovascular events. We compared 3 measures of renal function—serum cystatin C, serum creatinine, and calculated creatinine clearance—as predictors of subsequent cardiovascular events in a community-based population of elderly individuals. Methods: Comprehensive cardiovascular risk factor data were available for 1410 surviving participants of previous Busselton health surveys who were ≥60 years old. Hazard ratios for risk of incident coronary heart disease and cardiovascular disease over 10 years of follow-up were derived for each baseline measure of renal function by use of Cox regression. Results: All measures of renal function were significantly related to risks of morbidity and mortality from coronary heart disease and cardiovascular disease. There were 453 incident cardiovascular disease events; and the age- and sex-adjusted hazard ratios (95% CIs) were 1.34 (1.23–1.46), 1.32 (1.20–1.45), and 1.22 (1.06–1.41) per 1-SD deterioration in cystatin C, creatinine, and creatinine clearance, respectively. All 3 measures gave approximately the same age-adjusted relative risk estimates. After further adjustment for established cardiovascular risk factors, the relative risk estimates were all reduced but remained statistically significant (P &lt; 0.05). Cystatin C was not a significant predictor for cardiovascular disease after adjustment for creatinine clearance. Conclusions: In relation to predicting risk for coronary heart disease or cardiovascular disease over a 10-year follow-up in a community-based population of elderly subjects, there was no evidence that cystatin C was a better risk predictor than creatinine or creatinine clearance.

scholarly journals Lipoprotein(a)-Lowering by 50 mg/dL (105 nmol/L) May Be Needed to Reduce Cardiovascular Disease 20% in Secondary Prevention

2020 ◽  
Vol 40 (1) ◽  
pp. 255-266 ◽  
Author(s):  
Christian M. Madsen ◽  
Pia R. Kamstrup ◽  
Anne Langsted ◽  
Anette Varbo ◽  
Børge G. Nordestgaard
Keyword(s):  
Cardiovascular Disease ◽  
General Population ◽  
Secondary Prevention ◽  
Major Adverse Cardiovascular Event ◽  
Incidence Rates ◽  
Adverse Cardiovascular Event ◽  
General Population Study ◽  
Lipoprotein A ◽  
Disease Study ◽  
Rate Ratios

Objective: High Lp(a) (lipoprotein[a]) cause cardiovascular disease (CVD) in a primary prevention setting; however, it is debated whether high Lp(a) lead to recurrent CVD events. We tested the latter hypothesis and estimated the Lp(a)-lowering needed for 5 years to reduce CVD events in a secondary prevention setting. Approach and Results: From the CGPS (Copenhagen General Population Study; 2003–2015) of 58 527 individuals with measurements of Lp(a), 2527 aged 20 to 79 with a history of CVD were studied. The primary end point was major adverse cardiovascular event (MACE). We also studied 1115 individuals with CVD from the CCHS (Copenhagen City Heart Study; 1991–1994) and the CIHDS (Copenhagen Ischemic Heart Disease Study; 1991–1993). During a median follow-up of 5 years (range, 0–13), 493 individuals (20%) experienced a MACE in the CGPS. MACE incidence rates per 1000 person-years were 29 (95% CI, 25–34) for individuals with Lp(a)<10 mg/dL, 35 (30–41) for 10 to 49 mg/dL, 42 (34–51) for 50 to 99 mg/dL, and 54 (42–70) for ≥100 mg/dL. Compared with individuals with Lp(a)<10 mg/dL (18 nmol/L), the multifactorially adjusted MACE incidence rate ratios were 1.28 (95% CI, 1.03–1.58) for 10 to 49 mg/dL (18–104 nmol/L), 1.44 (1.12–1.85) for 50 to 99 mg/dL (105–213 nmol/L), and 2.14 (1.57–2.92) for ≥100 mg/dL (214 nmol/L). Independent confirmation was obtained in individuals from the CCHS and CIHDS. To achieve 20% and 40% MACE risk reduction in secondary prevention, we estimated that plasma Lp(a) should be lowered by 50 mg/dL (95% CI, 27–138; 105 nmol/L [55–297]) and 99 mg/dL (95% CI, 54–273; 212 nmol/L [114–592]) for 5 years. Conclusions: High concentrations of Lp(a) are associated with high risk of recurrent CVD in individuals from the general population. This study suggests that Lp(a)-lowering by 50 mg/dL (105 nmol/L) short-term (ie, 5 years) may reduce CVD by 20% in a secondary prevention setting.

Abstract 2231: Thoracic Aortic Calcification and Coronary Heart Disease Events: the Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Matthew J Budoff ◽  
Khurram Nasir ◽  
Ronit Katz ◽  
Junichiro Takasu ◽  
J Jeffrey Carr ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Population Based ◽  
Risk Factor Modification ◽  
Chd Risk ◽  
Hazard Ratios ◽  
Coronary Events ◽  
Thoracic Aortic Calcification ◽  
Independent Marker

Background: The presence of coronary artery calcium (CAC) is an independent marker of cardiovascular disease (CVD) events and mortality. However, the predictive value of thoracic aorta calcification (TAC), which can be additionally examined without further scanning during assessment of CAC, in predicting coronary heart disease (CHD) events in asymptomatic women and men, is not well-established. Methods: We collected data on risk factors and performed scanning for both TAC and CAC in a multi-ethnic population-based cohort of 6809 individuals (62±10 years, 47% males). Using the same images for each participant, TAC and CAC were computed using the Agatston method. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 4.1 years. Results: The mean age of the study population was 62±10 years (47% males). At baseline 1904 (28%) participants had detectable TAC, whereas 3392 (50%) had CAC>0. During the follow-up interval, 189 (2.78%) and 108 (1.59%) participants suffered any CHD and hard CHD event, respectively. Table below provide the hazard ratio (95% CI) for coronary events with presence of TAC. Overall TAC was a stronger predictor of CHD risk in women than in men. . Conclusion: Our study result suggests that TAC imparts independent prognostic power to predict future coronary events in women and may provide rationale for more intensive risk factor modification. Hazard Ratios (95% CI) of All CHD and Hard CHD Events with TAC (TAC>0 vs. TAC=0)

scholarly journals Association of weight fluctuation with cardiovascular disease risk among initially obese adults

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seogsong Jeong ◽  
Seulggie Choi ◽  
Jooyoung Chang ◽  
Kyuwoong Kim ◽  
Sung Min Kim ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Weight Loss ◽  
Heart Disease ◽  
Weight Gain ◽  
Weight Maintenance ◽  
Weight Cycling ◽  
Obese Adults ◽  
Weight Fluctuation ◽  
Increased Risk

AbstractThe association of fluctuations in body mass index with cardiovascular risk in long-term is not well understood. This study aimed to investigate cardiovascular outcomes of weight fluctuation. Total of 67,101 obese adults from the Korean National Health Insurance Service who received health examinations in three separate biennial periods were included. Participants were followed up from January 1, 2008 to the date of cardiovascular disease, death, or December 31, 2015, and categorized into 9 distinctive groups according to the BMI. Continuous weight gain showed an increased risk of overall cardiovascular disease (hazard ratio [HR], 2.36; P = 0.007), whereas weight loss after weight maintenance (HR, 0.91; P = 0.016) and weight maintenance after weight loss (HR, 0.91; P = 0.004) were ameliorative compared to the no weight change group. As for coronary heart disease, weight maintenance after weight gain was unfavorable (HR, 1.25; P = 0.004) while weight loss after weight maintenance (HR, 0.82; P < 0.001), weight cycling (HR, 0.83; P = 0.043), and weight maintenance after weight loss (HR, 0.88; P = 0.012) were beneficial. Weight maintenance after weight loss is beneficial for obese adults in terms of cardiovascular risks. In addition, weight loss is in part related to reduced risk of coronary heart disease despite weight cycling.

Increased risk of coronary heart disease among patients with idiopathic inflammatory myositis: a nationwide population study in Taiwan

Rheumatology ◽  
2019 ◽  
Vol 58 (11) ◽  
pp. 1935-1941 ◽  
Author(s):  
Meng-Yu Weng ◽  
Edward Chia-Cheng Lai ◽  
Yea-Huei Kao Yang
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Cohort Study ◽  
Heart Disease ◽  
Health Insurance ◽  
Cardiovascular Risk ◽  
General Population ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Idiopathic Myositis

Abstract Objective To evaluate the risk of incident coronary heart disease (CHD) among patients with DM and PM in a general population context. Methods We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database containing records covering the years from 2000 to 2010. DM and PM were confined for the purposes of this study to those aged ⩾18 years who were eligible for the Taiwan catastrophic illness certificate. The diagnoses, CHD outcomes and cardiovascular risk factors were identified from electronic claims data. We conducted two cohort analyses: CHD and DM, and CHD and PM, excluding for each analysis individuals with CHD already identified at baseline. Data for the comparison group was obtained from the Longitudinal Health Insurance database, comprising 1 million persons randomly sampled from the total beneficiaries during 2000. We estimated hazard ratios comparing myositis with comparison cohorts, adjusting for potential cardiovascular risk factors. Results A total of 1145 patients with idiopathic myositis were identified, along with 732 723 control patients aged ⩾18 years. The incidence rates of CHD were 15.1 in DM and 30.1 in PM per 1000 person-years, vs 8.4 and 10.5 per 1000 person-years in the comparison cohort. The adjusted hazard ratios for CHD in patients with idiopathic myositis were 2.21 (95% CI 1.64, 2.99) for DM and 3.73 (95% CI 2.83, 4.90) for PM. Conclusion Results of this general population-based cohort study suggest that DM and PM are associated with an increased risk of CHD.

scholarly journals Association between prediabetes and risk of all cause mortality and cardiovascular disease: updated meta-analysis

BMJ ◽  
2020 ◽  
pp. m2297 ◽  
Author(s):  
Xiaoyan Cai ◽  
Yunlong Zhang ◽  
Meijun Li ◽  
Jason HY Wu ◽  
Linlin Mai ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
General Population ◽  
Confidence Interval ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Atherosclerotic Cardiovascular Disease ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Objective To evaluate the associations between prediabetes and the risk of all cause mortality and incident cardiovascular disease in the general population and in patients with a history of atherosclerotic cardiovascular disease. Design Updated meta-analysis. Data sources Electronic databases (PubMed, Embase, and Google Scholar) up to 25 April 2020. Review methods Prospective cohort studies or post hoc analysis of clinical trials were included for analysis if they reported adjusted relative risks, odds ratios, or hazard ratios of all cause mortality or cardiovascular disease for prediabetes compared with normoglycaemia. Data were extracted independently by two investigators. Random effects models were used to calculate the relative risks and 95% confidence intervals. The primary outcomes were all cause mortality and composite cardiovascular disease. The secondary outcomes were the risk of coronary heart disease and stroke. Results A total of 129 studies were included, involving 10 069 955 individuals for analysis. In the general population, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.13, 95% confidence interval 1.10 to 1.17), composite cardiovascular disease (1.15, 1.11 to 1.18), coronary heart disease (1.16, 1.11 to 1.21), and stroke (1.14, 1.08 to 1.20) in a median follow-up time of 9.8 years. Compared with normoglycaemia, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 7.36 (95% confidence interval 9.59 to 12.51), 8.75 (6.41 to 10.49), 6.59 (4.53 to 8.65), and 3.68 (2.10 to 5.26) per 10 000 person years, respectively. Impaired glucose tolerance carried a higher risk of all cause mortality, coronary heart disease, and stroke than impaired fasting glucose. In patients with atherosclerotic cardiovascular disease, prediabetes was associated with an increased risk of all cause mortality (relative risk 1.36, 95% confidence interval 1.21 to 1.54), composite cardiovascular disease (1.37, 1.23 to 1.53), and coronary heart disease (1.15, 1.02 to 1.29) in a median follow-up time of 3.2 years, but no difference was seen for the risk of stroke (1.05, 0.81 to 1.36). Compared with normoglycaemia, in patients with atherosclerotic cardiovascular disease, the absolute risk difference in prediabetes for all cause mortality, composite cardiovascular disease, coronary heart disease, and stroke was 66.19 (95% confidence interval 38.60 to 99.25), 189.77 (117.97 to 271.84), 40.62 (5.42 to 78.53), and 8.54 (32.43 to 61.45) per 10 000 person years, respectively. No significant heterogeneity was found for the risk of all outcomes seen for the different definitions of prediabetes in patients with atherosclerotic cardiovascular disease (all P>0.10). Conclusions Results indicated that prediabetes was associated with an increased risk of all cause mortality and cardiovascular disease in the general population and in patients with atherosclerotic cardiovascular disease. Screening and appropriate management of prediabetes might contribute to primary and secondary prevention of cardiovascular disease.

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