The ankle-brachial index for assessing the prevalence of peripheral artery disease and cardiovascular risk in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) is an important risk factor for peripheral artery disease (PAD). Ankle-Brachial Index (ABI) was found associated with a higher cardiovascular (CV) risk and mortality. The main goals of this study were to establish the prevalence of PAD in a T2DM population, and assess the relationship between PAD and the CV risk calculated with the CUORE Project score (CPS) (https://www.cuore.iss.it/). The association between the ABI, the main risk factors for PAD and T2DM complications was also investigated. METHODS AND RESULTS: Two hundred patients were consecutively enrolled. The prevalence of PAD in this population was 17%. The CV risk tended to be higher (p = 0.0712) in the group with a pathological ABI than in the group with a normal ABI. Glycated hemoglobin (r = -0.1591; p = 0.0244), total cholesterol (r = -0.1958; p = 0.0054), LDL cholesterol (r = -0.1708; p = 0.0156) and systolic blood pressure (r = -0.1523; p = 0.0313) correlated significantly and inversely with the left ABI. The frequency of diabetic retinopathy was significantly higher in the group with a pathological ABI (p = 0.0316). CONCLUSIONS: The data reveal a high prevalence of PAD in patients with T2DM. The CPS confirmed that patients with a pathological ABI have tendency to a higher CV risk. The results point to the importance of an accurate CV assessment - also measuring individuals' ABI and calculating their CPS - to better pinpoint those at high risk of PAD, especially among patients with T2DM.

Association between ankle-brachial blood pressure index with all-cause and cardiovascular mortality in adults without arterial stiffness.

PURPOSE: To explore the relationship between ankle-brachial blood pressure index (ABPI) and all-cause or cardiovascular mortality in adults without arterial stiffness. METHODS: A total of 6784 participants without arterial stiffness were enrolled from National Health and Nutrition Examination Survey 1999-2004. The hazard ratio (HR) and 95% confidence interval (CI) of ABPI associating with the risk of all-cause and cardiovascular mortality was calculated by Cox proportional regression models adjusted for demographic and traditional risk factors. Dose-response relationship was explored with restricted cubic spines. RESULTS: After an average follow-up of 12.1 years, 1844 all-cause deaths and 299 cardiovascular deaths occurred. Compared with the lowest ABPI quartile, the second quartile was associated with the lowest risk of all-cause mortality (HR 0.89, 95%CI 0.79-0.98; p = 0.036) and cardiovascular mortality (HR 0.75, 95%CI 0.56-0.98; p = 0.048). Besides, dose-response analysis revealed that ABPI was nonlinearly correlated to all-cause mortality (p for nonlinearity < 0.001) and linearly correlated to cardiovascular mortality (p for nonlinearity = 0.459). CONCLUSIONS: The relationship between ABPI and all-cause and cardiovascular mortality followed a L-shape curve. A lower ABPI was independently associated with an increased risk of all-cause and cardiovascular mortality in adults without arterial stiffness.

Socioeconomic characteristics of those with peripheral artery disease in the chronic renal insufficiency cohort.

BACKGROUND: The association between socioeconomic factors and peripheral arterial disease (PAD) has not been as well characterized as other cardiovascular conditions. We sought to define how annual income and education level are associated with PAD in a well-characterized diverse set of adults with chronic kidney disease (CKD). METHODS: The Chronic Renal Insufficiency Cohort Study (CRIC) is a multi-center, prospective cohort study designed to examine risk factors for progression of CKD and cardiovascular disease. Demographic, income, and education-level data, as well as clinical data including ankle-brachial index (ABI) were collected at baseline. Annual income was categorized as < $25,000, $25,000-50,000, $50,000-100,000, or above $100,000; educational level was categorized as some high school, high school graduate, some college, or college graduate. Participants with missing income data or incompressible ABI (>1.4) were excluded from initial analysis. Logistic regression was used to estimate the association of income and/or education level with PAD, defined as an enrollment ABI of <0.90, history of PAD, or history of PAD intervention. RESULTS: A total of 4122 were included, mean age of participants was 59.5 years, 56% were male, and 44% were Black. There were 763 CRIC participants with PAD at study enrollment (18.5%). In the final multivariable logistic regression model, Black race (OR = 1.3, 95% CI 1.1-1.6, p = 0.004) and level of annual household income remained independently associated with PAD at the time of enrollment (income <$25,000 OR = 1.9, 95% CI 1.3-2.8, p < 0.001; income $25,000-50,000 OR = 1.6, 95% CI 1.1-2.3, p = 0.011; income $50,000-100,000 OR = 1.2, 95% CI 0.9-1.8, p = 0.246), relative to a baseline annual income of >$100,000 (overall p-value <0.001). Decreasing level of educational attainment was not independently associated with increased PAD at enrollment, but lower level of educational attainment was associated with increased PAD when income data was not adjusted for (p = 0.001). Interestingly, Black race (OR = 0.7, 95% CI 0.6-0.8, p < 0.001), female gender (OR = 0.8, 95% CI 0.7-0.9, p = 0.007), and income <$25,000 (OR = 0.7, 95% CI 0.5-0.9, p = 0.008) were significantly associated with decreased statin use even after controlling for cardiovascular conditions. CONCLUSIONS: In this prospectively followed CKD cohort, lower annual household income and Black race were significantly associated with increased PAD at study enrollment. In contrast, educational level was not associated with PAD when adjusted for patient income data. Black race, female gender, and low income were independently associated with decreased statin use, populations which could be targets of future public health programs.

Cardio-ankle brachial index is associated with prolonged Tp-e interval in patients with arterial hypertension.

AIM: The cardio-ankle vascular index (CAVI) is a marker of arterial stiffness, and elevated CAVI values have been reported to be associated with an increased risk of cardiovascular mortality and cardiac arrhythmia. This study aimed to evaluate the relationship between Tp-e interval and CAVI, which is associated with cardiac arrhythmia on electrocardiography (ECG). METHOD: The study included patients with hypertension whose blood pressure values were taken under control with optimal medical treatment. Arterial stiffness and CAVI were measured using the vascular scanning system VaSera VS-1000. The patients were divided into two groups as CAVI<9 and CAVI≥9. Ventricular repolarization markers QT and QTc intervals, Tp-e interval, and Tp-e/QT and Tp-e/QTc ratios were measured using 12­lead ECG. RESULTS: Tp-e interval (78.7 ± 10.3 vs. 63.6 ± 9.1, p < 0.001), Tp-e/QT ratio (0.018 ± 0.02 vs. 0.015 ± 0.02, p < 0.001), and Tp-e/QTc ratio (0.17 ± 0.02 vs. 0.14 ± 0.04, p = 0.025) were statistically significantly higher in the CAVI≥9 group compared to the CAVI<9 group. In the prediction of patients in the CAVI≥9 group, Tp-e interval had an area under the curve value of 0.862 (0.784-0.940, p < 0.001) at the cut-off point of >72.5 msec, indicating a statistically significant result. Left CAVI and right CAVI were found to be significantly correlated with Tp-e interval (r = -0.650, p < 0.001 and r = -0.663, p < 0.001, respectively). CONCLUSION: We found that elevated CAVI values were associated and positively correlated with prolonged Tp-e interval values in patients with hypertension. Patients with elevated CAVI values should be followed up closely to prevent cardiac arrhythmic events.

Statin use improves survival of patients with known or suspected lower extremity artery disease on all ankle brachial index levels.

Background: Statin medication improves the prognosis of patients with lower extremity artery disease (LEAD). Research has previously focused on patients with a lowered ankle brachial index (ABI) excluding patients with a normal or elevated ankle brachial index. The aim of this study was to analyze the impact of statin use on survival and cardiovascular mortality in patients with LEAD of different severity depicted by the ABI level. Patients and methods: 4128 ABI measurements by trained and experienced nurses between 2000 and 2009 were combined with medication data from the Social Insurance Institution and causes of death data from the national causes of death registry. End of follow-up was set at the end of 2014. The data of statin use included all statin medication with the Anatomical Therapeutic Chemical (ATC) classification codes between C10AA01 and C10AA08. Results: 1956 (47.4%) patients had statin medication. Statin use was associated with improved overall survival and amputation free survival (AFS) on all ABI levels. When adjusted for age, sex and diabetes the greatest overall survival benefit from statin use was for the patients with ABI>1.3 (hazard ratio, HR: 0.67, 95% CI: 0.48-0.94, p=0.020, reference group statin non-users) and ABI 0.9-1.3 (HR: 0.78, 95% CI: 0.65-0.94, p=0.008). In propensity score matched pairs statin treatment was associated with significantly lower all-cause mortality (p<0.0001), cardiovascular mortality (p=0.034), cerebrovascular mortality (p=0.003) and embolic stroke related mortality (p=0.001) in patients with ABI >1.3 or <0.9. Overall survival benefit was significant in females with ABI<0.5 and in males across several ABI levels. Conclusions: According to our study, statins seem to improve overall and amputation free survival regardless of ABI level. Statin use was associated with lower mortality from cerebrovascular disease, overall mortality and in the propensity score matched patients with ABI<0.9 or >1.3 with cardiovascular mortality.

Diagnostic Accuracy of Point-of-care Tests Used to Detect Arterial Disease in Diabetes: TEsting for Arterial Disease in Diabetes (TrEAD) Study.

OBJECTIVE: We compared the diagnostic performance of a novel point-of-care duplex ultrasound test (podiatry ankle duplex scan; PAD-scan) against commonly used bedside tests for the detection of PAD in diabetes. BACKGROUND: PAD is a major risk factor for diabetic foot ulceration and amputation. Its diagnosis is fundamental though challenging. Although a variety of bedside tests are available, there is no agreement as to which is the most useful. PAD-scan may be advantageous over current tests as it allows for vessel visualization and more accurate arterial waveform assessment. However, its accuracy has not been previously evaluated. METHODS: From March to October 2019, we recruited 305 patients from 2 diabetic foot clinics. The diagnostic performance of ankle-brachial pressure index, toe-brachial pressure index, transcutaneous pressure of oxygen, pulse palpation, and ankle waveform assessment using PAD-scan and Doppler devices (audible and visual waveform assessment) were assessed. The reference test was a full lower limb duplex ultrasound. RESULTS: Based on the reference test, 202 (66.2%) patients had evidence of PAD. PAD-scan had a significantly higher sensitivity [95%, confidence interval (CI) 90%-97%) as compared to all other tests. Particularly low sensitivities were seen with pulse palpation (43%, CI 36%-50%) and transcutaneous pressure of oxygen (31%, CI 24%-38%). PAD-scan had a lower specificity (77%, CI 67%-84%) compared to toe-brachial pressure index (86%, CI 78%-93%; P < 0.001), but not statistically different when compared to all other tests. CONCLUSIONS: PAD-scan has superior diagnostic utility and is a valid first line investigation.

Peripheral artery disease and all-cause and cardiovascular mortality in patients with NAFLD.

PURPOSE: Cardiovascular disease (CVD) is the first cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and risk stratification is recommended by current guidelines. The aim of this study is to assess the prevalence of peripheral arterial disease (PAD) in patients with NAFLD and its association with all-cause and cardiovascular disease (CVD) mortality. METHODS: 9145 participants 40 years or older attended a mobile examination center visit in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. PAD was defined as an ankle-brachial index (ABI) < 0.90 in either of the legs and mortality data through December 2015 were obtained from the National Death Index. NAFLD was defined by a fatty liver index ≥ 60 in the absence of other liver conditions, leading to a final sample of 3094 subjects. RESULTS: The overall prevalence of PAD was 5.9% (95% CI 5.0-6.9). Over a median follow-up of 13 years, 876 participants died, 208 of cardiovascular causes. Incidence rates of all-cause mortality (for 1000 person-years) were 20.2 (95% CI 18.7-21.7) and 70.0 (95% CI 60.1-81.6) for participants without and with PAD, respectively. Multivariable-adjusted Cox proportional hazard models showed that PAD was associated with a higher risk of all-cause (1.8, 95% CI 1.4-2.4) and cardiovascular mortality (HR 2.5, 95% CI 1.5-4.3) after adjustment for potential confounders including prevalent CVD. CONCLUSION: Current guidelines strongly encourage the screening of CVD in patients with NAFLD and the use of the simple and inexpensive measurement of ABI in routine clinical practice may find indication.

Screening for Peripheral Artery Disease Using the Ankle-Brachial Index: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Peripheral artery disease (PAD) is associated with a high risk for cardiovascular events and poor ambulatory function, even in the absence of symptoms. Screening for PAD with the ankle-brachial index (ABI) may identify patients in need of treatment to improve health outcomes. Objective: To systematically review evidence for the US Preventive Services Task Force on PAD screening with the ABI, the diagnostic accuracy of the test, and the benefits and harms of treatment of screen-detected PAD. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published between January 2012 and May 2, 2017. Surveillance continued through February 7, 2018. Study Selection: Studies of unselected or generally asymptomatic adults with no known cardiovascular disease. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Main Outcomes and Measures: Cardiovascular morbidity; PAD morbidity; mortality; health-related quality of life; diagnostic accuracy; and serious adverse events. Results: Five studies (N = 5864 participants) were included that examined the indirect evidence for the benefits and harms of screening and treatment of screen-detected PAD. No population-based screening trials evaluated the direct benefits or harms of PAD screening with the ABI alone. A single diagnostic accuracy study of the ABI compared with magnetic resonance angiography gold-standard imaging (n = 306) found low sensitivity (7%-34%) and high specificity (96%-100%) in a screening population. Two adequately powered trials (n = 4626) in asymptomatic populations with and without diabetes with a variably defined low ABI (≤0.95 or ≤0.99) showed no statistically significant effect of aspirin (100 mg daily) for composite CVD outcomes (adjusted hazard ratio [HR], 1.00 [95% CI, 0.81-1.23] and HR, 0.98 [95% CI, 0.76-1.26]). One trial (n = 3350) demonstrated no statistically significant increase in major bleeding events with the use of aspirin (adjusted HR, 1.71 [95% CI, 0.99- 2.97]) and no statistically significant increase in major gastrointestinal bleeding (relative risk, 1.13 [95% CI, 0.44-2.91]). Two exercise trials (n = 932) in screen-relevant populations reported no differences in quality of life, Walking Impairment Questionnaire walking distance, or symptoms at 12 and 52 weeks; no harms were reported. Conclusions and Relevance: There was no direct evidence and limited indirect evidence on the benefits of PAD screening with the ABI in unselected or asymptomatic populations. Available studies suggest low sensitivity and lack of beneficial effect on health outcomes, but these studies have important limitations.

Screening for Peripheral Artery Disease and Cardiovascular Disease Risk Assessment With the Ankle-Brachial Index: US Preventive Services Task Force Recommendation Statement.

Importance: Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the lower limbs. It can impair walking and, in severe cases, can lead to tissue loss, infection, and amputation. In addition to morbidity directly caused by PAD, patients with PAD are at increased risk for cardiovascular disease (CVD) events, because atherosclerosis is a systemic disease that also causes coronary and cerebrovascular events. Objective: To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on screening for PAD and CVD risk with the ankle-brachial index (ABI). Evidence Review: The USPSTF reviewed the evidence on whether screening for PAD with the ABI in generally asymptomatic adults reduces morbidity or mortality from PAD or CVD. The current review expanded on the previous review to include individuals with diabetes and interventions that include supervised exercise and physical therapy intended to improve outcomes in the lower limbs. Findings: The USPSTF found few data on the accuracy of the ABI for identifying asymptomatic persons who can benefit from treatment of PAD or CVD. There are few studies addressing the benefits of treating screen-detected patients with PAD; 2 good-quality studies showed no benefit of using the ABI to manage daily aspirin therapy in unselected populations, and 2 studies showed no benefit from exercise therapy. No studies addressed the harms of screening, although the potential exists for overdiagnosis, labeling, and opportunity costs. Studies that addressed the harms of treatment showed nonsignificant results. Therefore, the USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for PAD with the ABI in asymptomatic adults cannot be determined. Conclusions and Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults. (I statement).

Relationship between addictions and obesity, physical activity and vascular aging in young adults (EVA-Adic study): a research protocol of a cross-sectional study.

Background: Behavioral and substance addictions are prevalent health problems that, alongside obesity, are linked to reduced physical activity and increased sedentary time. Similarly, arterial stiffness and vascular aging are processes that begin gradually at an early age and are closely associated with morbidity and mortality from cardiovascular diseases. The main objective of this study is to analyze how addictions are related to obesity and body fat distribution, physical activity, sedentary time, arterial stiffness and vascular aging, as well as sleep quality, cognitive function and gender differences in young adults aged between 18 and 34 years. Methods: This cross-sectional descriptive observational study will analyze data from 500 subjects (250 men and 250 women) aged 18-34 without cardiovascular disease, selected by simple random sampling with replacement from the urban population of the city center of Salamanca (34,044 people aged 18-34, with 18,450 women and 15,594 men). Behavioral and substance addictions, as well as sleep quality and cognitive impairment will be assessed using questionnaires. The Pittisburg Sleep Quality Index (PSQI) will be used to measure sleep quality and the Ford questionnaire will be used to measure insomnia in response to stress. For obesity, weight, height, waist and hip circumference, body composition will be measured with the Inbody 230® impedance meter. For physical activity and sedentary time, we will use the Actigraph® accelerometer alongside the international physical activity questionnaire (IPAQ) and the Marshall questionnaire. The Sphygmocor System® will be used for pulse wave analysis and carotid-femoral pulse wave velocity (cfPWV), while the Vasera VS-2000® will measure cardio ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Vascular aging will be calculated with the 10th and 90th percentiles of cfPWV or baPWV. Demographic, analytical variables will be collected, as will data to assess vascular, cardiac, renal, and brain injury. Discussion: Addictions are on the rise in today's society, affecting the mental health and well-being of those who suffer from them, generating important social problems such as job loss, family dysfunction, debt and social isolation. Together with obesity, they are prevalent health problems in young adults and are associated with lower physical activity and higher sedentary time. Meanwhile, arterial stiffness and vascular aging are processes that begin gradually at an early age and determine morbidity and mortality caused by cardiovascular diseases. The results of this project will allow us to understand the situation regarding behavioral and substance addictions in young adults. Better understanding of these addictions will in turn facilitate the development of more effective prevention strategies and intervention programs, which can then reduce the negative impact at both the individual and societal levels. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05819840].

Evaluation of changes in glycemic control and diabetic complications over time and factors associated with the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications. METHODS: We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis. RESULTS: Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors. CONCLUSIONS: In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis.

Pivotal trial of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from CMERC-HI.

OBJECTIVE: The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk. MATERIALS AND METHODS: In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) according to Reti-CVD in prediction of CVD events. The cardiac computed tomography-measured coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial-ankle pulse wave velocity (baPWV) were compared to Reti-CVD. RESULTS: A total of 1106 participants were included, with 33 (3.0%) participants experiencing CVD events over 5 years; the Reti-CVD-defined risk groups (low, moderate, and high) were significantly associated with increased CVD risk (HR trend, 2.02; 95% CI, 1.26-3.24). When all variables of Reti-CVD, CAC, CIMT, baPWV, and other traditional risk factors were incorporated into one Cox model, the Reti-CVD risk groups were only significantly associated with increased CVD risk (HR = 2.40 [0.82-7.03] in moderate risk and HR = 3.56 [1.34-9.51] in high risk using low-risk as a reference). DISCUSSION: This regulated pivotal study validated an AI-SaMD, retinal image-based, personalized CVD risk scoring system (Reti-CVD). CONCLUSION: These results led the Korean regulatory body to authorize Reti-CVD.

Study protocol for a multicentre comparative diagnostic accuracy study of tools to establish the presence and severity of peripheral arterial disease in people with diabetes mellitus: the DM PAD study.

INTRODUCTION: Peripheral arterial disease (PAD) is a key risk factor for cardiovascular disease, foot ulceration and lower limb amputation in people with diabetes. Early diagnosis of PAD can enable optimisation of therapies to manage these risks. Its diagnosis is fundamental, though challenging in the context of diabetes. Although a variety of diagnostic bedside tests are available, there is no agreement as to which is the most accurate in routine clinical practice.The aim of this study is to determine the diagnostic performance of a variety of tests (audible waveform assessment, visual waveform assessment, ankle brachial pressure index (ABPI), exercise ABPI and toe brachial pressure index (TBPI)) for the diagnosis of PAD in people with diabetes as determined by a reference test (CT angiography (CTA) or magnetic resonance angiography (MRA)). In selected centres, we also aim to evaluate the performance of a new point-of-care duplex ultrasound scan (PAD-scan). METHODS AND ANALYSIS: A prospective multicentre diagnostic accuracy study (ClinicalTrials.gov Identifier NCT05009602). We aim to recruit 730 people with diabetes from 18 centres across the UK, covering primary and secondary healthcare. Consenting participants will undergo the tests under investigation. Reference tests (CTA or MRA) will be performed within 6 weeks of the index tests. Imaging will be reported by blinded consultant radiologists at a core imaging lab, using a validated scoring system, which will also be used to categorise PAD severity. The presence of one or more arterial lesions of ≥50% stenosis, or tandem lesions with a combined value of ≥50%, will be used as the threshold for the diagnosis of PAD. The primary outcome measure of diagnostic performance will be test sensitivity. ETHICS AND DISSEMINATION: The study has received approval from the National Research Ethics Service (NRES) (REC reference 21/PR/1221). Results will be disseminated through research presentations and papers. TRIAL REGISTRATION NUMBER: NCT05009602.

Screen-detected abnormal ankle brachial index: A risk indicator for future cardiovascular morbidity and mortality in patients with manifest cardiovascular disease.

OBJECTIVES: The ankle brachial index (ABI) can be used to diagnose peripheral arterial disease (PAD). The clinical relevance of the ABI, especially in patients with known clinically manifest cardiovascular disease (CVD), is unknown. The authors set out to investigate the relationship between a screen-detected ABI and the risk for future cardiovascular morbidity and mortality in patients with clinically manifest CVD. DESIGN, MATERIALS AND METHODS: Patients with clinically manifest CVD were selected from the UCC-SMART cohort (n = 8360) and divided into four groups: normal ABI (0.91-1.39), screen-detected low ABI ≤ 0.9, screen-detected high ABI ≥ 1.4, and patients with known PAD irrespective of their ABI. Adjusted Cox Proportional Hazard Ratios (HRs) for Major Adverse Cardiovascular Events (MACE), Major Adverse Limb Events (MALE), and all-cause mortality were calculated. In addition, stratified analyses for women and men and for the presence of diabetes were performed. RESULTS: During a median follow-up of 8.3 years (IQR 7.7) 1646 MACE, 601 MALE and 1958 all-cause mortalities were observed. Compared with normal ABI patients, patients with a screen-detected low ABI and patients with manifest PAD had a higher risk of MACE, MALE, and all-cause mortality with HRs of 1.9 (95% CI 1.6-2.2) for MACE, 7.6 (95% CI 5.7-10.1) for MALE, 1.7 (95% CI 1.5-2.0) for mortality and 1.3 (95% CI 1.2-1.5) for MACE, 13.8 (95% CI 11.1-17.1) for MALE, 1.7 (95% CI 1.5-1.9) for mortality, respectively. Screen-detected high ABI did not increase the risk of either MACE or MALE, however, was associated with lower risk of all-cause mortality with a HR of 0.6 (95% CI 0.5-0.9). Stratified analyses for women & men and for diabetes status were comparable for all three outcomes. CONCLUSIONS: In patients with manifest CVD but without PAD, a screen-detected low ABI is a powerful risk indicator for cardiovascular events, limb events, and all-cause mortality.

Combined impact of elevated arterial stiffness and left ventricular filling pressure on outcomes after off-pump coronary artery bypass grafting.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV) and early diastolic transmitral flow velocity to mitral annular tissue velocity (E/e')-which are markers of arterial stiffness and left ventricular (LV) filling pressure, respectively-have been associated with morbidity and mortality. We investigated their combined impact on postoperative complications and long-term survival of patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS: A cohort of 164 patients were divided into four groups: baPWV ≤ 19 m/s and E/e' ≤ 15 (reference), baPWV > 19 m/s and E/e' ≤ 15 (high-PWV-only), baPWV ≤ 19 m/s and E/e' > 15 (high-E/e'-only), and baPWV > 19 m/s and E/e' > 15 (high-PWV-and-E/e'). After inverse probability treatment weighting adjustment, each group was compared with the reference group to analyze the odds ratios of postoperative complications and the Kaplan-Meier survival curves, and to identify the group representing an independent prognostic predictor. RESULTS: The median age and follow-up duration were 69 years and 57.2 months, respectively. Both postoperative acute kidney injury (POAKI) and atrial fibrillation (POAF) were higher in the high-PWV-and-E/e' group (adjusted odds ratio (OR) = 89.5; 95% confidence interval (CI), 8.5-942.3; p < 0.001 and OR = 12.5; CI, 2.5-63.8; p = 0.002, respectively). Compared to the reference group, only the high-PWV-and-E/e' group showed significantly lower survival rate (91.0%; CI, 82.8-100% vs. 44.8%; CI, 21.2-94.6%) and a higher hazard for all-cause mortality after adjustment for covariates (hazard ratio = 6.1; p = 0.002). CONCLUSION: Concurrent elevation in PWV and E/e' may independently affect not only the rates of POAKI and POAF but also long-term survival after OPCAB.

Ankle-brachial index predicts renal outcomes and all-cause mortality in high cardiovascular risk population: a nationwide prospective cohort study in CORE project.

BACKGROUND: Low ankle-brachial index (ABI) related ischemic events are common among individuals with chronic kidney disease (CKD). It is also associated with an increased risk of rapid renal function decline. The presence of peripheral artery disease (PAD) with low ABI among patients with high cardiovascular (CV) risk increases limb loss and mortality. AIMS: To estimate the association between abnormal ABI and renal endpoints and all-cause mortality. METHODS: A multicenter prospective cohort study was conducted among subjects with high CV risk or established CV diseases in Thailand. The subjects were divided into 3 groups based on ABI at baseline > 1.3, 0.91-1.3, and ≤ 0.9, respectively. Primary composite outcome consisted of estimated glomerular filtration rate (eGFR) decline over 40%, eGFR less than 15 mL/min/1.73 m2, doubling of serum creatinine and initiation of dialysis. The secondary outcome was all-cause mortality. Cox regression analysis and Kaplan-Meier curve were performed. RESULTS: A total of 5543 subjects (3005 men and 2538 women) were included. Cox proportional hazards model showed a significant relationship of low ABI (ABI ≤ 0.9) and primary composite outcome and all-cause mortality. Compared with the normal ABI group (ABI 0.91-1.3), subjects with low ABI at baseline significantly had 1.42-fold (95% CI 1.02-1.97) and 2.03-fold (95% CI 1.32-3.13) risk for the primary composite outcome and all-cause mortality, respectively, after adjusting for variable factors. CONCLUSION: Our study suggested that PAD independently predicts the incidence of renal progression and all-cause mortality among Thai patients with high CV risk.

Comprehensive cardiac rehabilitation program for peripheral arterial diseases.

Peripheral arterial disease (PAD) is a phenotype of atherosclerotic disease often associated with cerebrovascular or coronary artery disease. The incidence of cardiovascular events in patients with PAD is 5.4% per year, which is higher than that of cerebrovascular or coronary artery disease. The most useful screening method for PAD is the ankle brachial pressure index (ABI). The ABI should be measured in (1) all patients with lower limb symptoms such as claudication, (2) all patients aged 65 years and over, and (3) those aged 50 to 65 years who have risk factors such as smoking and diabetes mellitus. PAD is diagnosed if the ABI is <0.9. A comprehensive cardiac rehabilitation program includes complete smoking cessation, blood pressure control with antihypertensive medications and salt reduction for hypertension, glycemic control for diabetes mellitus, and appropriate medications such as antiplatelet agents and statins. A multidisciplinary team approach is effective in comprehensive cardiac rehabilitation for patients with PAD, even those with critical limb ischemia (CLI). Exercise therapy is a crucial and essential treatment for PAD, except in CLI. Exercise therapy is contraindicated in patients with acute arterial occlusion and CLI with infection. PAD is often associated with other atherosclerotic diseases; the patient should be monitored for ischemic heart disease during the initial exercise stress test using the Gardner treadmill protocol. Supervised exercise therapy is highly recommended (Class I, Level of Evidence A). Alternatively, a home-based exercise program is feasible (Class IIa, Level of Evidence A). The exercise type (treadmill, track walking, ergometer), frequency (3 to 5 days per week), intensity (speed and incline), and duration (30 minutes) are determined based on the exercise stress test results for each patient. Exercise should be continued at least 3 times a week for at least 12 weeks. Cilostazol is highly recommended (Class I, Level of Evidence A).

Association between baseline brachial-ankle pulse wave velocity and short-term risk of first stroke among Chinese hypertensive adults.

Little information is available on the association between brachial-ankle pulse wave velocity (baPWV) and the risk of stroke in Chinese H-type hypertension patients. Therefore, our study aimed to assess this association between baseline baPWV and short-term risk of first stroke and to propose a cutoff value of baPWV that could predict near cerebrovascular events. A total of 9787 hypertension patients without preexisting stroke who underwent baPWV measurement were included. The primary end points were first symptomatic stroke. Secondary end points were first ischemic stroke and first hemorrhagic stroke. During a median follow-up of 20.8 months, there was a total of 138 first strokes including 123 first ischemic strokes and 15 first hemorrhagic strokes. When baPWV was categorized in quartiles, the higher risks of first stroke (HR = 1.52; 95% CI: 1.05-2.21) and first ischemic stroke (HR = 1.53; 95% CI: 1.03-2.26) were found in participants in quartile 4 (≥21.31 m/s), compared with those in quartile 1-3 (<21.31 m/s). In receiver operating characteristic curve analysis, the best cutoff value of baPWV that could predict first stroke was 21.43 m/s. Higher baPWV (≥21.43 m/s) was significantly associated with increased risk of first stroke (HR = 1.60; 95% CI: 1.10-2.32) and first ischemic stroke (HR = 1.60; 95% CI: 1.08-2.37). In conclusion, higher baPWV levels were associated with an increased risk of first stroke among Chinese H-type hypertensive patients. In addition, a cutoff value of 21.43 m/s of baPWV was proposed that could predict the next two years' cerebrovascular events.

Subclinical atherosclerosis associates with diabetic retinopathy incidence: a prospective study.

BACKGROUND: The prospective correlation between subclinical atherosclerosis and diabetic retinopathy (DR) incidence in Chinese patients with type 2 diabetes mellitus (T2DM) remains elusive. METHODS: Prospective data were obtained from 2781 patients with diabetes, among whom 1,964 and 2,180 T2DM patients without any and referable DR at baseline, respectively, were included in the analysis. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Over a median follow-up of 22.2 months (interquartile range 12.7-27.7), 282 (14.36%) and 125 (5.73%) patients developed any and referable DR, respectively. After adjustment for confounders, each standard deviation (SD) increase in brachial-ankle pulse wave velocity (ba-PWV) was associated with 31% (95% confidence interval 1.15-1.50) and 38% (1.14-1.66) higher risks of incident any and referable DR, respectively. Compared with the lowest ba-PWV quartile, the highest ba-PWV quartile had 135% (1.48-3.72) and 293% (1.83-8.44) higher risks of developing any and referable DR, respectively. Per SD increase of pulse pressure (PP) was associated with 22% (1.09-1.38) and 22% (1.02-1.46) higher risks of incident any and referable DR, respectively. The restricted cubic spline models further indicated a significant linear association of baseline subclinical atherosclerosis with referable DR, and a nonlinear association with any DR. In addition, adding the ba-PWV to the prognostic model for DR incidence improved the C-statistic value, the integrated discrimination improvement value, and the net reclassification improvement value (all P < 0.05). CONCLUSIONS: Baseline subclinical atherosclerosis was significantly associated with an increased risk of DR incidence, and elevated ba-PWV independently predicted incident DR in T2DM patients.