Acute Myocardial Infarction Caused by Coronary Spasm and Dissection Treated with Medical Therapy.

We report the case of a 33-year-old woman with no history of coronary risk factors or chest pain who experienced intermittent chest pain at rest for several minutes from 2 PM. At 8 AM the next day, chest pain recurred and persisted for about 1 hour. She was transported to our hospital by ambulance, where electrocardiogram showed ST-elevation in the precordial leads, and blood tests showed elevation of cardiac markers. She was diagnosed with ST-elevation myocardial infarction. Because she was a young woman without any risk factors, coronary spastic angina was suspected. Coronary angiography without intracoronary nitrate administration revealed diffuse 75% stenosis in the proximal right coronary artery (RCA) and diffuse 90% stenosis in the left anterior descending artery (LAD). A coronary spasm provocation test elicited chest pain; coronary angiography showed 99% diffuse stenosis of LAD; and electrocardiogram showed precordial ST-segment elevation. Although intracoronary nitroglycerin injection attenuated the coronary spasm in the RCA and proximal LAD, 90% stenosis and coronary dissection were observed in the midportion of the LAD. When the imaging test that was carried out before the provocation test was reexamined, the dissection was recognized, and there was no clear dissection progress after the test. Intravascular ultrasound showed dissection of the LAD, as did angiography. We treated the patient using medical therapy instead of percutaneous coronary intervention.The patient did not suffer any anginal attack and improved sufficiently to be discharged. She remained free of attacks for about 10 years to the present time, and follow-up is continuing.

Endovascular therapy and free flap transfer in chronic limb-threatening ischemia.

Although revascularization has evolved, treating foot gangrene with chronic limb-threatening ischemia remains challenging. There have been many reports on bypass surgery and free flap transfer. Meanwhile, few studies have reported on endovascular therapy and free flap transfer, with high flap survival rates and high wound complication rates. Wound complications are a serious problem that can lead to limb amputation, but previous studies have failed to identify risk factors for wound complications. In this study, we evaluated the results of endovascular therapy and free flap transfer for chronic limb-threatening ischemia and analyzed risk factors for wound complications. A total of 31 legs from 28 patients who underwent endovascular therapy and free flap transfer for lower limb salvage between August 2016 and April 2020 were retrospectively reviewed. The primary endpoints were flap survival and limb salvage rates and wound complication rates. In addition, we performed a statistical analysis of risk factors for wound complications. The flap survival rate was 100%, with partial necrosis in 6% of the patients. The limb salvage rate was 100%. The wound complication rate was 45%. The multivariate analysis showed end-stage renal failure on dialysis as a significant risk factor for wound complications (odds ratio = 133, 95% confidence interval = 2.74-6430, p = 0.014). Endovascular therapy and free flap transfer in chronic limb-threatening ischemia achieved high flap survival rate and limb salvage, but had a high incidence of wound complications. We identified end-stage renal failure on dialysis was a significant risk factor for wound complications.

Acute impact of apheresis on oxidized phospholipids in patients with familial hypercholesterolemia.

We measured oxidized phospholipids (OxPL), lipoprotein (a) [Lp(a)], and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) pre- and postapheresis in 18 patients with familial hypercholesterolemia (FH) and with low(∼10 mg/dl; range 10-11 mg/dl), intermediate (∼50 mg/dl; range 30-61 mg/dl), or high (>100 mg/dl; range 78-128 mg/dl) Lp(a) levels. By using enzymatic and immunoassays, the content of OxPL and Lp-PLA(2) mass and activity were quantitated in lipoprotein density fractions plated in microtiter wells, as well as directly on apoB-100, Lp(a), and apoA-I immunocaptured within each fraction (i.e., OxPL/apoB and Lp-PLA(2)/apoB). In whole fractions, OxPL was primarily detected in the Lp(a)-containing fractions, whereas Lp-PLA(2) was primarily detected in the small, dense LDL and light Lp(a) range. In lipoprotein capture assays, OxPL/apoB and OxPL/apo(a) increased proportionally with increasing Lp(a) levels. Lp-PLA(2)/apoB and Lp-PLA(2)/apoA-I levels were highest in the low Lp(a) group but decreased proportionally with increasing Lp(a) levels. Lp-PLA(2)/apo(a) was lowest in patients with low Lp(a) levels and increased proportionally with increasing Lp(a) levels. Apheresis significantly reduced levels of OxPL and Lp-PLA(2) on apoB and Lp(a) (50-75%), particularly in patients with intermediate and high Lp(a) levels. In contrast, apheresis increased Lp-PLA(2)-specific activity (activity/mass ratio) in buoyant LDL fractions. The impact of apheresis on Lp(a), OxPL, and Lp-PLA(2) provides insights into its therapeutic benefits beyond lowering apoB-containing lipoproteins.

Sacral Pressure Ulcer in Leriche Syndrome: A Case Report.

We experienced a case of a sacral pressure ulcer complicated with Leriche syndrome, an aortoiliac artery occlusion that has not been previously reported. In this case, the abdominal aorta below the bifurcation of the renal arteries into the bilateral common iliac arteries was occluded, and wound healing was delayed. Therefore, endovascular treatment was used for managing this condition, and wound healing was accelerated. Then, reconstructive surgery with a local flap was performed, and wound healing was achieved. In the case of delayed healing of buttock pressure ulcers, it is important to evaluate the blood flow in the iliac artery as well as the infection and nutritional status of the wound. In addition, after endovascular treatment, blood flow in the local flap is a matter of concern. If the wound healing is good, and imaging confirms that there is no restenosis at the endovascular treatment site and the perforator of the flap, reconstructive surgery can be performed safely.

Hyperbaric oxygen therapy for digital ulcers due to Raynaud's disease.

We present a case of Raynaud's disease with digital ulcers that was successfully treated with hyperbaric oxygen therapy. Hyperbaric oxygen therapy can be considered as a safe and useful adjunct treatment for intractable digital ulcers in patients with Raynaud's disease.

Lipoprotein(a) for risk assessment in patients with established coronary artery disease.

OBJECTIVES: The purpose of this study was to assess the prognostic utility of lipoprotein(a) [Lp(a)] in individuals with coronary artery disease (CAD). BACKGROUND: Data regarding an association between Lp(a) and cardiovascular (CV) risk in secondary prevention populations are sparse. METHODS: Plasma Lp(a) was measured in 6,708 subjects with CAD from 3 studies; data were then combined with 8 previously published studies for a total of 18,978 subjects. RESULTS: Across the 3 studies, increasing levels of Lp(a) were not associated with the risk of CV events when modeled as a continuous variable (odds ratio [OR]: 1.03 per log-transformed SD, 95% confidence interval [CI]: 0.96 to 1.11) or by quintile (Q5:Q1 OR: 1.05, 95% CI: 0.83 to 1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quantile were at increased risk of CV events (OR: 1.40, 95% CI: 1.15 to 1.71), but with significant between-study heterogeneity (p = 0.001). When stratified on the basis of low-density lipoprotein (LDL) cholesterol, the association between Lp(a) and CV events was significant in studies in which average LDL cholesterol was ≥130 mg/dl (OR: 1.46, 95% CI: 1.23 to 1.73, p < 0.001), whereas this relationship did not achieve statistical significance for studies with an average LDL cholesterol <130 mg/dl (OR: 1.20, 95% CI: 0.90 to 1.60, p = 0.21). CONCLUSIONS: Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.

Oxidized phospholipids are present on plasminogen, affect fibrinolysis, and increase following acute myocardial infarction.

OBJECTIVES: This study sought to assess whether plasminogen, which is homologous to lipoprotein (a) [Lp(a)], contains proinflammatory oxidized phospholipids (OxPL) and whether this has clinical relevance. BACKGROUND: OxPL measured on apolipoprotein B-100 (OxPL/apoB), primarily reflecting OxPL on Lp(a), independently predict cardiovascular disease (CVD) events. METHODS: The authors examined plasminogen from commercially available preparations and plasma from chimpanzees; gorillas; bonobos; cynomolgus monkeys; wild-type, apoE(-/-), LDLR(-/-), and Lp(a)-transgenic mice; healthy humans; and patients with familial hypercholesterolemia, stable CVD, and acute myocardial infarction (AMI). Phosphocholine (PC)-containing OxPL (OxPC) present on plasminogen were detected directly with liquid chromatography-mass spectrometry (LC-MS/MS) and immunologically with monoclonal antibody E06. In vitro clot lysis assays were performed to assess the effect of the OxPL on plasminogen on fibrinolysis. RESULTS: LC-MS/MS revealed that OxPC fragments were covalently bound to mouse plasminogen. Immunoblot, immunoprecipitation, density gradient ultracentrifugation, and enzyme-linked immunosorbent assay analyses demonstrated that all human and animal plasma samples tested contained OxPL covalently bound to plasminogen. In plasma samples subjected to density gradient fractionation, OxPL were present on plasminogen (OxPL/plasminogen) in non-lipoprotein fractions but on Lp(a) in lipoprotein fractions. Plasma levels of OxPL/apoB and OxPL/apo(a) varied significantly (>25×) among subjects and also strongly correlated with Lp(a) levels. In contrast, OxPL/plasminogen levels were distributed across a relatively narrow range and did not correlate with Lp(a). Enzymatic removal of OxPL from plasminogen resulted in a longer lysis time for fibrin clots (16.25 vs. 11.96 min, p = 0.007). In serial measurements over 7 months, OxPL/plasminogen levels did not vary in normal subjects or in patients with stable CVD, but increased acutely over the first month and then slowly decreased to baseline in patients following AMI. CONCLUSIONS: These data demonstrate that plasminogen contains covalently bound OxPL that influence fibrinolysis. OxPL/plasminogen represent a second major plasma pool of OxPL, in addition to those present on Lp(a). OxPL present on plasminogen may have pathophysiological implications in AMI and atherothrombosis.

The I4399M variant of apolipoprotein(a) is associated with increased oxidized phospholipids on apolipoprotein B-100 particles.

OBJECTIVES: The LPA I4399M (rs3798220) single nucleotide polymorphism (SNP) is associated with increased plasma levels of Lp(a) and advanced coronary artery disease (CAD). We hypothesized that carriers of the Met allele of the I4399M SNP would also have elevated levels of oxidized phospholipids (OxPL) on apoB (OxPL/apoB) particles. METHODS AND RESULTS: Plasma levels of Lp(a) and OxPL/apoB were measured in non-carriers (TT genotype, n=116) and carriers (CT/CC genotype, n=58) of the I4399M SNP. Carriers had significantly higher Lp(a) levels [median (interquartile range, IQR)] [43 (9-57)mg/dl vs. 5.5 (2-20)mg/dl, p<0.0001] and smaller apolipoprotein(a) isoforms than non-carriers (number of kringle IV repeats: 18(17-20) vs. 22(18-25), p=0.002). Median (IQR) OxPL/apoB levels were significantly higher in carriers than non-carriers [8019 (6254-31,785) relative light units (RLU) vs. 2168 (1303-5869), p<0.0001]. Patients with small apolipoprotein(a) isoforms had the highest OxPL/apoB levels. The number of kringle IV repeats was inversely related to Lp(a) (r=-0.43, p<0.001) and OxPL/apoB (r=-0.36, p<0.0001) levels. CONCLUSION: The CT and CC genotypes of the I4399M SNP in the LPA gene are associated with elevated OxPL/apoB levels, which primarily represent OxPL on Lp(a). The concomitant increase of OxPL/apoB levels in the setting of small apolipoprotein(a) isoforms may potentiate the atherogenic effect on CAD of elevated Lp(a) levels in carriers of the I4399M SNP.