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Research theme and design
A total of 2130 consecutive patients at risk for PAD who attended the cardiovascular outpatient department of Mackay Memorial Hospital between August 2009 and December 2014 were retrospectively recruited. Eligible study participants were diagnosed with advanced age (men >45 years, women >55 years), history of hypertension, type 2 diabetes, hypercholesterolemia, and high-density lipoprotein cholesterol (men <40 mg/dl, women <50 mg). /dl), known heart failure (HF), cerebrovascular events, CAD, or smoking history.
Patients with documented significant valvular heart disease (more than moderate valvular heart disease) have decreased LV systolic HF (left ventricular ejection fraction ≥40%), regardless of whether they undergo surgical correction. , documented congenital heart disease, recent acute coronary syndrome, and known cardiomyopathy were excluded from the data collection process at the time patient information was collected. All demographic data and medical history were collected during a face-to-face interview by three independent cardiologists. All participants underwent biochemical testing.
We initiated a screening process for PAD because patients with certain risk factors, such as increasing age, DM, HTN, and smoking, are at higher risk for PAD. All patients underwent evaluation including measurements of right and left brachial-ankle pulse wave velocity (ba-PWV), femoral-ankle PWV (fa-PWV), right ABI, and left ABI. Transthoracic echocardiography was performed within her 2 weeks of the ABI study to rule out structural abnormalities and assess preclinical systolic dysfunction using speckle tracking-based deformity measurements. The diagnosis of HFpEF was established within his 3 months of ABI study.
Initially, patients were divided into two groups based on their risk of developing PAD. One group was designated as the high-risk her PAD group and the other group was designated as the low-risk non-PAD group as determined by the results of his ABI study. . Within these groups, further classification was then made based on the risk of developing PAD with and without HFpEF. This classification process is visually represented in Supplementary Figure 1 and serves as the basic framework for the subsequent analysis of heart failure hospitalization rates, all-cause mortality, CV mortality, and non-CV mortality. This study was approved by the local Institutional Review Board (McKay Memorial Hospital Institutional Review Board) (15MMHIS031e), and informed consent was waived due to the retrospective nature of the study. The conduct of this study was conducted in accordance with the Declaration of Helsinki.
Anthropometric and baseline risk factor measurements
Anthropometric parameters such as height, weight, and waist circumference were measured by experienced research nurses. Hypertension is measured in two different ways, or antihypertensive drugs. Hypercholesterolemia was defined as total cholesterol ≥200 mg/dl, low-density lipoprotein cholesterol ≥130 mg/dl, or use of lipid-lowering drugs (statins or fibrates). . Diabetes was defined as fasting blood glucose >126 mg/dl or use of DM medications, and smoking history was defined as former or current smoker.
CAD was defined as a condition characterized by a documented history of acute coronary syndrome, clinical symptoms indicative of CAD, or the presence of >50% coronary artery stenosis confirmed by CT or angiography. This definition includes cases with or without percutaneous intervention (such as angioplasty) or the need for coronary artery bypass grafting. The diagnosis of CAD was confirmed at the time patient information was collected.
Renal function was assessed by estimated glomerular filtration rate as follows: eGFR = 186.3 × (serum creatinine)~1.154) × (age~0.203) × 0.742 (for women).
Measuring pulse wave velocity (PWV) or ankle-brachial index (ABI)
ABI and PWV were measured by an experienced technician and one rater. After resting in the supine position for 5 min, bilateral ba-PWV, fa-PWV, systolic blood pressure, and diastolic blood pressure from the extremities were measured using gates with an automated machine (VP-2000; Corin Co., Ltd., Japan). Did. Electrocardiogram (ECG) (Figure 1). Her PWV, as one measure of arterial stiffness, is calculated as the distance between two arterial sites divided by the time delay between the two arterial sites and is expressed as centimeters/second. His ABI on the left and right side was calculated by the highest pressure in the dorsal or posterior tibial artery on the right and left sides, respectively, and the highest brachial pressure on either side. Of each patient’s two ABI measurements, the lowest ABI was selected for study.

Illustration of ABI/PWV waveforms and overall longitudinal contractile function from deformation measurements. (a) One patient with a normal ABI value (1.01) but no clinical HF diagnosis (as non-PAD/non-HFpEF) and relatively preserved longitudinal systolic tone (right, 4-chamber view from). (B) Another patient in this study had a normal ABI value (1.14) with a previous HFpEF diagnosis (as non-PAD/HFpEF) and a normal arterial tracing waveform from the lower extremity (left, blue arrow) and decreased overall had a longitudinal systolic strain pattern (right, right). 4-chamber view). ECG, peripheral artery disease. HEpEF, heart failure with preserved ejection fraction; GLS, global longitudinal strain; LVEF, left ventricular ejection fraction.
Establishment of high risk of developing PAD patients
As recommended by the American College of Cardiology and American Heart Association (ACC/AHA) guidelines, ABI results should be consistently reported as follows: Uncompacted values are defined as greater than 1.40; is in the range 1.00. 1.40 euro, between 0.91 and 0.99 is the boundary value, and below 0.90 is an abnormal value. In our study, we followed recommendations for defining high risk of developing peripheral arterial disease (PAD) by considering participants with an ankle-brachial index (ABI) ≥0.90 or ABI ≥. 1.4 on each side of the leg. It is important to emphasize that these participants did not undergo imaging tests to confirm the presence of PAD and did not exhibit symptoms of PAD. As a result, we decided to refer to them as “high risk for developing PAD” rather than explicitly classifying them as having PAD.
Measurement of echocardiographic parameters
Two-dimensional echocardiography was performed according to the recommendations of the American Society of Echocardiography. Left ventricular ejection fraction (LVEF) was measured using the Simpson biplane method.Ten Left ventricular (LV) mass index, relative wall thickness (RWT), left artery (LA) diameter, isovolumic relaxation time (IVRT), and deceleration time (DT) were also measured. In the septal and lateral rings, LV e₂ was measured using tissue Doppler and the E/e₂ ratio was calculated. Advanced echocardiographic imaging uses strain imaging to assess cardiac function, including measurements of global longitudinal strain (GLS) (Figure 1) and global circumferential strain (GCS). was executed with.The offline workstation from our laboratory, the algorithms used, and speckle tracking variations for GLS/GCS measurements have been previously publishedTen. Preclinical systolic dysfunction was defined as GLS impairment with a value of GLS ≥ 18%)11.
Laboratory measurements
Overnight fasted serum and plasma samples were collected for biochemical measurements including glucose, lipid profile (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), and renal function. Serum samples were collected in standard sampling tubes or separate gel-containing tubes. After securing individual patient samples, calibrators and controls were set at ambient temperature (20–25 °C) and measurements were taken within 2 hours. High-sensitivity C-reactive protein (hs-CRP) levels were measured using a high-sensitivity latex particle-enhanced immunoassay using Elecsys 2010 (Hitachi, Ltd., Hitachinaka, Ibaraki, Japan). Serum B-type natriuretic peptide (BNP) concentrations were measured using a fluorescence immunoassay microtiter plate (Alere Biosite Triage, San Diego Inc. Ca, USA) with a coefficient of variation (CV) of 10.4%. Renal function was determined by estimating glomerular filtration rate (eGFR), which was calculated using the Modification of Dietary Treatment in Renal Disease (MDRD) formula.
statistical analysis
Continuous data are expressed as the mean and its standard deviation (SD), and categorical variables are expressed as proportions or percentages. Mann-Whitney U tests were used to examine trends in demographic information based on risk of developing PAD and HFpEF. Univariate linear regression models were utilized to investigate the relationship between ABI parameters (including minimum ABI, fa-PWV, and ba-PWV) and cardiac performance indices such as E/eⓇ, GLS, and GCS. These models allowed us to assess the association between these variables. We employed a series of statistical models, both univariate and multivariate, adjusting for potential confounders. These models were applied in four strata based on high risk of developing PAD and HFpEF, using the non-PAD/non-HFpEF group as a reference.
In the first model, we adjusted for age and gender, recognizing the influence of these demographic factors on the results. The second model then included additional adjustments for age, gender, and BMI to account for the potential influence of her BMI on the results. The third model incorporated a broader set of adjustments that considered age, gender, and also hypertension, diabetes, coronary CAD, atrial fibrillation, hyperlipidemia, smoking status, eGFR, and LV mass index. I am.
The results of these univariate and multivariate Cox models were analyzed for various endpoints including heart failure hospitalization, all-cause mortality, CV mortality, and non-CV mortality. To visualize the differences in these outcomes between groups with different risks of developing PAD and HFpEF, survival curves were constructed using the Kaplan-Meier survival estimator and compared between different risk groups.
All statistical analyzes were two-tailed; P≦0.05 is considered statistically significant. Statistical analyzes were performed using IBM Statistics (version 26.0; SPSS Inc., Armonk, NY, USA).
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