Colchicine may reduce inflammation in metabolic syndrome

Colchicine may reduce inflammation in metabolic syndrome

Obesity and especially metabolic syndrome are pro-inflammatory conditions, that can give rise to hypertension, dyslipidemia, insulin resistance, diabetes, and cardiovascular disease. Colchicine, an anti-inflammatory agent, is frequently used for gout, pericarditis and familial Mediterranean fever.

In this small randomized clinical trial, authors found that colchicine 0.6 mg twice daily decreased inflammatory markers CRP, ESR, WBC, and ANC in patients with obesity and metabolic syndrome. These results could provide some basis for designing outcome-driven clinical trials, such as evaluating diabetes and CVD risk reduction with colchicine.

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2019 NLA scientific statement: Lp(a) - key points

2019 NLA scientific statement: Lp(a) - key points

The various large meta-analysis, Mendelian randomizations, and prospective population-based studies have found the Lipoprotein (a) to be an independent risk factor for atherosclerosis, aortic valve stenosis, and thrombosis. Lp(a) test is considered to be high when its value is >50 mg/dL or >100 nmol/L. These measures correspond to the top 20th percentile of the general population.

Currently, there are no approved specific therapies for Lp(a). The NLA does not recommend the use of Niacin, HRT (hormonal replacement therapy) or Lomitapide (microsomal triglyceride transfer protein inhibitor). Recent trials such as FOURIER and ODYSSEY have shown that addition of PCSK9 inhibitors to Statin therapy can lower Lp(a) by 30%.

However, various guidelines including 2018 AHA/ACC and 2019 NLA scientific statement recommend the use of PCSK9 inhibitors only in the context of uncontrolled LDLc/non-HDLc in patients at high-risk or very-high-risk for ASCVD events.

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Coronary microvascular dysfunction in women

Coronary microvascular dysfunction in women

It is important to be aware of the atypical pathology and manifestation of coronary artery disease in women. This case shows the inappropriate withholding of heart medications in an 83-year-old female due to ischemic nonobstructive coronary artery disease, also called INOCA. Coronary microvascular dysfunction (CMD) is considered the main pathogenesis of INOCA.

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Vyleesi for hypoactive sexual desire disorder

Vyleesi for hypoactive sexual desire disorder

Vyleesi has been approved for generalized hypoactive sexual desire disorder (HSDD) in women younger than age 50. It is self-injected subcutaneously 45 minutes prior to the anticipated sexual intercourse. It should not be used more than 8 times per month and more than once daily. In a short-term randomized clinical trial, Vyleesi performed better than placebo. Although Vyleesi activates melanocortin receptors, its precise mechanism of action in HSDD is unknown.

Side effects include increased blood pressure, nausea, vomiting, headache, and darkening of the gums. It should be avoided in patients with uncontrolled hypertension or cardiovascular disease. This approval occurs in the context of FDA’s 2012 ruling of considering female sexual dysfunction as one of the top 20 high priority conditions. Its cost and health insurance coverage will determine its accessibility and usage.

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Lipoprotein(a) is an independent ASCVD risk

Lipoprotein(a) is an independent ASCVD risk

Blood Lipoprotein(a) measurements are genetically determined.  Lifestyle, physical activity or dietary habits do not change its levels.  Epidemiologically, Lp(a) has been found to be an independent risk factor for poor ASCVD outcomes.  Lp(a) is a promoter of atherosclerosis, thrombosis and aortic valve stenosis.

In this meta-analysis of 7 statin-outcome randomized clinical trials, authors showed that baseline and on-statin treatment Lp(a) levels correlated positively and linearly with ASCVD events: the higher the Lp(a) measurements, the higher the cardiovascular outcomes.

Development of specific drug therapies in reducing Lp(a) are needed.  These therapies would then be tested in outcome driven ASCVD clinical trials.

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New drug development for hypercholesterolemia

New drug development for hypercholesterolemia

The study shows that bempedoic acid, when added to statin therapy, reduces LDLc levels further. Bempedoic acid is an inhibitor of ATP citrate lyase, an important enzyme of cholesterol and fatty acid synthesis.

A group of 2300 patients with either established cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) were followed for about 12 months.  Baseline LDLc was 103 mg/dL.  Mean LDLc reduction with bempedoic acid was about 20 mg/dL.

These results are meaningful as it is well-established that the lower the LDLc the lower the ASCVD outcomes.  No increased adverse events were seen with the ATP Citrate lyase inhibitor compared to placebo.

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ACLY variants vs. cardiovascular outcomes

ACLY variants vs. cardiovascular outcomes

ATP citrate lyase is a key enzyme in cholesterol and fatty acid biosynthesis. It helps convert citrate to Acetyl CoA, the precursor to endogenous lipid genesis. Recent studies have shown that pharmacological inhibition of ATP citrate lyase causes a 30% reduction in LDLc, 50% reduction when combined with ezetimibe, and an extra 20% LDLc lowering when added to statin therapy.

This major Mendelian randomization study revealed that genetic variants in the ACLY gene led to similar clinical and biochemical outcomes as HMGCR variants. This provides a theoretical basis that medical inhibition of ATP citrate lyase could have similar cardiovascular benefits as statin therapies.

Mendelian randomization is considered nature’s randomized “clinical trial”. About 800,000 participants were included and analyzed.

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Aspirin is useful in diabetes but increases the risk of bleeding

Aspirin is useful in diabetes but increases the risk of bleeding

The major randomized clinical trial, ASCEND, shows that aspirin 100 mg daily lowers the rates of cardiovascular events by 12% in patients with diabetes but increases the risk of bleeding by 30%.

A group of 15,000 participants with diabetes but without baseline CVD were followed for about 7 years.

Case by case clinical judgment would be key in evaluating CVD benefits vs. bleeding risks of aspirin use in patients with diabetes.

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Thyroid hormones supplementation in pregnant women with Hashimoto’s thyroiditis

Thyroid hormones supplementation in pregnant women with Hashimoto’s thyroiditis

Thyroid hormones supplementation 50 mcg daily did not improve pregnancy outcomes in women with Hashimoto's thyroiditis in the presence of normal thyroid function.  Hashimoto’s thyroiditis was confirmed by elevated TPO antibodies at study entry. About 1,000 pregnant women were followed through full term.

This is an important study as it defies the current medical opinion of poorer pregnancy outcomes in euthyroid Hashimoto's thyroiditis.

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Bisphosphonate infusion for osteopenia

Bisphosphonate infusion for osteopenia

A group of 2,000 women with osteopenia receiving either zolendronate infusion or placebo were followed for 6 years. Zoledronate 5 mg or placebo were provided every 1.5 years. At the end of the study, the intravenous bisphosphonate reduced vertebral and nonvertebral fractions significantly by about 55% and 35% respectively.

Findings are of major significance as bisphosphonates in general and zolendronate specifically have been approved only for osteoporosis and not osteopenia. Would this expand indications for zoledronate? Should patients with osteopenia be treated or monitored?

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Invokana protects the heart and kidneys

Invokana protects the heart and kidneys

Patients with type 2 diabetes receiving Invokana experienced 30% and 20% lower rates of kidney disease progression and cardiovascular events respectively, when compared to the placebo group.

Results were so obvious and significant that the study was terminated early. About 4500 subjects with DM2 were followed for about 2.5 years. No increased rates of fractures or amputations were seen with Invokana.

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