Decreased free fatty acid levels associated with adverse clinical outcomes in coronary artery disease patients with type 2 diabetes: findings from the PRACTICE study.

AIMS: Increased free fatty acid (FFA) levels are known to be strongly associated with mortality in coronary artery disease (CAD) patients and the development of type 2 diabetes (T2DM). However, few studies have been large enough to accurately examine the relationship between FFA levels and mortality in CAD patients with T2DM. METHODS AND RESULTS: From December 2016 to October 2021, 10 395 CAD patients enrolled in PRACTICE, a prospective cohort study in China, were divided into four groups according to baseline FFA concentration. We investigated mortality, including all-cause mortality (ACM) and cardiac mortality (CM), as the primary endpoint. The secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs) and major adverse cardiovascular events (MACEs). The median follow-up time was 24 months. In the total cohort, there were 222 ACMs, 164 CMs, 718 MACEs, and 803 MACCEs recorded. After controlling for baseline variables, the association between FFA levels and the risk of mortality presented a non-linear U-shaped curve, with the lowest risk at 310 µmol/L. We also identified a non-linear U-shaped relationship for ischaemic events (MACE or MACCE) with the lowest risk at 500 µmol/L. Subgroup analysis showed that a U-shaped relationship between FFA and mortality or ischaemic events was observed only in individuals with T2DM but not in non-diabetic CAD patients. CONCLUSIONS: A non-linear U-shaped association was identified between baseline FFA levels and mortality or ischaemic events in CAD patients with T2DM.

From December 2016 to October 2021, 10 395 coronary artery disease (CAD) patients enrolled in PRACTICE, a prospective cohort study in China, were divided into four groups according to baseline free fatty acid (FFA) concentration. We investigated mortality, including all-cause mortality (ACM), and cardiac mortality (CM), as the primary endpoints. The secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs) and major adverse cardiovascular events (MACEs). The median follow-up time was 24 months. Finally, we were surprised to find that high and low FFA levels were associated with a higher risk of mortality and ischaemic events in CAD patients with T2DM. Baseline plasma FFA levels may be a more powerful, effective, and easily detectable biomarker of adverse outcomes in CAD patients with T2DM. As the FFA increases, a U-shaped curve appears in the poor long-term prognosis.

The Fibrinogen-to-Albumin Ratio Is Associated With Outcomes in Patients With Coronary Artery Disease Who Underwent Percutaneous Coronary Intervention.

Coronary artery disease (CAD) is a systemic chronic inflammatory disease, and serum fibrinogen and albumin are 2 important factors in systemic inflammation. We aimed to investigate the relationship between the fibrinogen-albumin ratio (FAR) and outcomes in patients with CAD who underwent percutaneous coronary intervention (PCI). All patients were from the Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI (CORFCHD-PCI) study, which is a retrospective cohort study (Identifier: ChiCTR-ORC-16010153) that includes a total of 6050 patients with CAD after PCI from January 2008 to December 2016. A total of 5829 patients with CAD after PCI were recruited in the present study. They were divided into 2 groups according to the FAR cutoff value, which was calculated using a receiver operating characteristic curve, a low group (FAR < 0.095, n = 3811), and a high group (FAR ≥ 0.095, n = 2018). The average follow-up time was 35.9 ± 22.6 months. The multivariate Cox proportional hazards model showed that FAR was independently correlated with all-cause mortality (adjusted hazard ratio [HR] = 1.432 [1.134-1.808], P = .003), cardiac mortality (adjusted HR = 1.579 [1.218-2.047], P = .001), major adverse cardiac and cerebrovascular events (adjusted HR = 1.296 [1.125-1.494], P < .001), major adverse cardiac events (adjusted HR = 1.357 [1.170-1.572], P < .001), and heart failure (adjusted HR = 1.540 [1.135-2.091], P = .006). The present study indicated that the FAR was associated with adverse outcomes in patients with CAD who underwent PCI.

Cascade reaction of alkynols with 1-(2-aminophenyl)prop-2-ynols to form a fused 5,5,6-tricyclic system: formation of four bonds in a single reaction.

A novel cascade reaction of internal alkynols with 1-(2-aminophenyl)prop-2-ynols has been developed to form a new N,O-containing fused 5,5,6-tricyclic skeleton. Mechanistic studies indicate that this reaction proceeds via alkynol cycloisomerization, intermolecular substitution with 1-(2-aminophenyl)prop-2-ynols, and intermolecular addition with alkynols and consequent cyclizations. In this way, two C-C bonds, one C-O bond and one C-N bond form to give a tricyclic skeleton in a single reaction.

Cu-Catalyzed Cascade Annulation of Alkynols with 2-Azidobenzaldehydes: Access to 6H-Isochromeno[4,3-c]quinoline.

A copper-catalyzed cascade reaction of alkynols and 2-azidobenzaldehydes has been achieved, giving 6H-isochromeno[4,3-c]quinoline in yields of 40-81%. This reaction provides a novel, concise strategy for rapidly constructing compounds with fused N- and O-containing heterocycles. In contrast to previously reported reactions of alkynols in which the first step is intramolecular cycloisomerization, the first step in this novel reaction of alkynols is entropically unfavorable intermolecular addition. The resulting hemiacetal intermediate then undergoes intramolecular cyclization and aromatization to afford the product.

Rhodium-catalyzed addition-cyclization of hydrazines with alkynes: pyrazole synthesis via unexpected C-N bond cleavage.

Rhodium-catalyzed addition-cyclization of hydrazines with alkynes has been achieved to afford highly substituted pyrazoles under mild conditions. The cascade reaction involves two transformations: addition of the C-N bond of hydrazines to alkynes via unexpected C-N bond cleavage and intramolecular dehydration cyclization.

Transition metal-free cascade reactions of alkynols to afford isoquinolin-1(2H)-one and dihydroisobenzofuran derivatives.

Transition metal-free cascade reactions of alkynols with imines have been achieved using potassium tert-butoxide as catalyst. Switching the reaction solvent gives two kinds of products in good yield: isoquinolin-1(2H)-one derivatives and dihydroisobenzofuran derivatives. This approach was used to generate the natural product 8-oxypseudopalmatine in a two-step procedure from commercially available starting materials. Additionally, multicomponent reactions of alkynols, aldehydes, and amines were also successfully achieved to afford isoquinolin-1(2H)-one derivatives.

Coordination self-assembly of bromo-phenyl and pyridyl functionalized porphyrins with Fe on an Au(111) surface.

Using scanning tunneling microscopy, the coordination self-assembly of a series of peripheral bromo-phenyl and pyridyl substituted porphyrins with Fe was studied on an Au(111) surface. The porphyrins functionalized with two trans-pyridyl groups afford extended hexagonal frameworks and the porphyrins functionalized with three pyridyl groups generate discrete rosette and extended chiral kagome framework structures. The self-assembly of the porphyrin derivatives in which phenyl groups are substituted by bromo-phenyl results in coordination networks exhibiting identical structures to that of the parent compounds. These structures contain nanocavities decorated with Br, which provide potential for covalent functionalization.