Aim: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk.

Methods: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2–3 hypertension groups, we defined “normal BP” as systolic/diastolic BP ＜130/＜80 mmHg and “high BP” as 130–139/80–89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death.

Results: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%–10.28%/3.83%–7.25%) in men/women with grade 2–3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women.

Conclusions: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments.

Aim: The aim of this study was to assess the association between weight change and mortality due to cardiovascular diseases (CVDs) in a Japanese population.

Methods: We used the data of a population-based prospective cohort study that was conducted from 1988 to 1990 in 45 areas throughout Japan. Among a total of 69,681 men and women aged 40–79 with no history of CVD or cancer at baseline, the association between weight change from 20 years of age to baseline and CVD-related mortality was evaluated.

Results: During a median follow-up period of 19.1 years, we observed 4,274 deaths from total CVD. After adjusting for age, sex, and other potential confounding factors, compared with participants with a weight change of ＜2.5 kg (stable weight), participants with a greater weight change (either loss or gain) had an increased risk of mortality from total CVD (U-shaped association). The hazard ratios for the total CVD risk in participants with a weight loss and a weight gain of ≥ 12.5 kg were 1.50 (95% confidence interval [CI], 1.30–1.72) and 1.21 (95% CI, 1.07–1.36), respectively. The associations between weight change and risk of mortality from ischemic heart disease or stroke showed similar trends. The risk of intracerebral hemorrhage was associated with weight loss only. Weight change was not associated with mortality from subarachnoid hemorrhage.

Conclusions: Weight loss or gain could be a risk factor for mortality from total or ischemic CVD, while weight loss could be a risk factor for intracerebral hemorrhage.

Aims: P-wave terminal force in lead V₁ (PTFV₁) is an electrocardiogram marker of increased left atrial pressure and may be a noninvasive and early detectable marker for future cardiovascular events in the general population compared to serum B-type natriuretic peptide (BNP) concentration. The clinical significance of PTFV₁ in the contemporary general population is an area of unmet need. We aimed to demonstrate the correlation between PTFV₁ and BNP concentrations in a contemporary representative Japanese population.

Methods: Among 2,898 adult men and women from 300 randomly selected districts throughout Japan (NIPPON DATA2010), we analyzed 2,556 participants without cardiovascular disease (stroke, myocardial infarction, and atrial fibrillation). Elevated BNP was defined as a value of ≥ 20 pg/mL based on the definition from the Japanese Circulation Society guidelines.

Results: In total, 125 (4.9%) participants had PTFV₁. Participants with PTFV₁ were older with a higher prevalence of hypertension, major electrocardiographic findings, and elevated BNP concentrations (13.5 [6.9, 22.8] versus 7.8 [4.4, 14.5] pg/mL; P＜0.001). After adjustment for confounders, PTFV₁ was correlated with elevated BNP (odds ratio, 1.66; 95% confidence interval, 1.05–2.62; P=0.030). This correlation was consistent among various subgroups and was particularly evident in those aged ＜65 years or those without a history of hypertension.

Conclusions: In the contemporary general population cohort, PTFV₁ was independently related to high BNP concentration. PTFV₁ may be an alternative marker to BNP in identifying individuals at a higher risk of future cardiovascular events in the East Asian population.

Aim: Recent studies suggested that past history of obesity or maximum body mass index (BMI) in the past was a strong prognostic predictor in a general population. The current study aimed to survey the distribution of current and maximum BMIs and to investigate their prognostic impact in patients with critical limb ischemia (CLI), whose prognosis was poor even after revascularization.

Methods: We analyzed a database of a prospective, multicenter registry in Japan, including 499 CLI patients undergoing revascularization. Their current and maximum BMIs were surveyed at registration. The distribution and the impact on the prognosis were explored.

Results: The estimated means (95% confidence intervals) of current and maximum BMIs were respectively 22.0 (21.7 to 22.3) and 25.3 (24.8 to 25.8) kg/m²; the difference was 3.3 (2.9 to 3.7) kg/m². The prevalence of current obesity (BMI ≥ 25 kg/m²) was 18% (15% to 22%), whereas 48% (43% to 53%) had ever been obese (maximum BMI ≥ 25 kg/m²). Past obesity was not rare even in currently lean subjects (BMI ＜18.5 kg/m²), with the prevalence of 18% (7% to 29%). Current BMI, but not maximum BMI, was associated with the mortality risk; the adjusted hazard ratios per 5 kg/m² increase were 0.61 [0.46, 0.81] (P=0.001) and 1.07 [0.87, 1.31] (P=0.55), respectively.

Conclusion: The prevalence of current obesity was as low as 18% (15% to 22%) in Japanese CLI patients undergoing revascularization, whereas about a half were formerly obese. Maximum BMI was not independently associated with the mortality risk in the population.

Aim: To investigate the associations between preoperative characteristics and the risk of reintervention in patients undergoing revascularization for chronic limb-threatening ischemia (CLTI) in a contemporary real-world setting.

Methods: We retrospectively analyzed data from a clinical database formed by the Surgical Reconstruction Versus Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) study, which was a multicenter, prospective, observational study. The study population was composed of 520 CLTI patients with the wound, ischemia, and foot infection (WIfI) classes I-3 with resting pain or classes I-2/3 with ulcers/gangrene. Of the 520 patients, 192 had surgical reconstruction planned, whereas 328 had endovascular therapy (EVT) alone planned at the time of registration. The current analysis was conducted to explore the associations between preoperative characteristics and the risk of reintervention.

Results: A total of 452 participants (87%) completed the 3-year follow-up regarding reintervention. The competing risk analysis estimated that the three-year cumulative incidence rates for reintervention and reintervention-free deaths were 44.0% and 28.7%, respectively. No preoperative characteristics had a significant interaction effect with EVT versus surgical reconstruction. The risk analysis identified the following independent risk factors for reintervention: 1) EVT instead of bypass reconstruction, 2) renal dysfunction, 3) history of revascularization after CLTI onset (i.e., requirement of redo revascularization for CLTI), and 4) bilateral CLTI. Patients with more than one of these risk factors had an increased risk of reintervention.

Conclusions: The current study identified preoperative characteristics associated with an increased risk of reintervention. No preoperative characteristics had any significant interactions with EVT or surgical reconstruction.

Aim: Deepening our understanding of the molecular mechanism of abdominal aortic aneurysm (AAA) progression will help set up novel avenues for therapeutic target identification. Our aim here was to unveil the mechanism function of STAT3 in AAA progression.

Methods: We investigated the functional role of STAT3 in AAA by evaluating vascular smooth muscle cell (VSMC) apoptosis and proliferation via terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting, 5-ethynyl-2´-deoxyuridine, and Cell Counting Kit-8 assays. The interplay of lncRNA-miRNA-mRNA was verified using the luciferase reporter assay and the RNA pull-down, RNA immunoprecipitation, and chromatin immunoprecipitation assays. Quantitative real-time polymerase chain reaction and western blot were utilized to quantitate the RNA and protein levels of the indicated molecules.

Results: Inhibition of STAT3 facilitated VSMC proliferation and repressed VSMC apoptosis. Moreover, It was demonstrated that small nucleolar RNA host gene 16 (SNHG16) sponged miR-106b-5p to release STAT3 from the inhibitory effect of miR-106b-5p. SNHG16 led to the upregulation of STAT3, and STAT3 was an upstream factor in the activation of SNHG16 transcription. Moreover, rescue experiments indicated that SNHG16 depended on STAT3 to regulate VSMC apoptosis and proliferation. In vivo assays showed that SNHG16 knockdown retarded the formation of AAA and upregulated STAT3 in vivo.

Conclusions: We identified that SNHG16/miR-106b-5p/STAT3 formed a complex circuitry for the deterioration of AAA via regulating VSMCs, suggesting a possible target for the pathogenesis of AAA.

Aim: The present study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in subjects at high cardiovascular risk.

Methods: A total of 3,080 participants without prior cardiovascular disease (CVD), aged ≥ 40 years, were followed up for a median of 8.3 years, which were divided into two groups, those with serum sdLDL cholesterol levels of ＜35 mg/dL or ≥ 35 mg/dL. Then, subjects were stratified by the status of diabetes, CVD-related comorbidities (defined as the presence of diabetes, chronic kidney disease, or peripheral artery disease), and the CVD risk assessment according to the Japan Atherosclerosis Society Guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using a Cox proportional hazards model.

Results: During the follow-up, 79 subjects developed CHD. The risk for incident CHD was higher in subjects with serum sdLDL cholesterol of ≥ 35 mg/dL than those with sdLDL cholesterol of ＜35 mg/dL (HR 2.09, 95%CI 1.26–3.45) after adjusting for traditional risk factors. In the subgroup analyses, the multivariable-adjusted HR for incident CHD increased significantly in those with serum sdLDL cholesterol of ≥ 35 mg/dL among subjects with diabetes (HR 2.76, 95%CI 1.09–7.01), subjects with CVD-related comorbidities (HR 2.60, 95%CI 1.21–5.58), and high-risk category defined as the presence of CVD-related comorbidities or a Suita score of ≥ 56 points (HR 1.93, 95%CI 1.02–3.65).

Conclusions: Elevated serum sdLDL cholesterol was associated with the development of CHD even in subjects at high cardiovascular risk.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly via the respiratory route. Elderly patients or those with underlying diseases are more seriously affected. We report a case of COVID-19 infection in a geriatric patient with arteriovenous thrombosis of the right lower limb. Despite persistent anticoagulant therapy, the patient's arterial thrombosis continued to progress and presented with ischemic necrosis of the lower extremity. After amputation in this case, the levels of D-dimer and inflammatory cytokine increased progressively, and he presented with acute myocardial infarction, which progressed rapidly to multisystem organ failure. However, whether coronavirus can directly cause the damage of the cardiovascular system and thrombosis needs further investigation.