Cardiovascular

2018 Cholesterol Guidelines: Key Points

2018 Cholesterol Guidelines: Key Points

Cardiovascular disease is the leading cause of death in the United States. Cholesterol anomaly, or dyslipidemia, is a major contributor to atherosclerosis morbidity and mortality. Multi-society new cholesterol guidelines were recently published. They were contributed and endorsed by ACC, AHA, ADA, and NLA, among other national associations. You can find below the key recommendations published in the journal of Circulation, November 2018.

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Early heart disease in diabetes and prediabetes

Early heart disease in diabetes and prediabetes

The study finds that the longer the duration of diabetes and prediabetes in early adulthood, the higher the risk of progressive subclinical atherosclerosis and cardiac pump dysfunction, in both phases of contractility and relaxation. About 3,600 patients of age 18-30 were followed for 25 years. This is yet another reason to screen and intervene aggressively young individuals for both prediabetes and diabetes.

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Ambulatory blood pressure monitoring (higher awareness is needed)

Ambulatory blood pressure monitoring (higher awareness is needed)

Ambulatory blood-pressure measurement (ABPM) refers to home assessments of blood pressure every 20-30 minutes over a 24 hour period. In this study about 64,000 adults were followed for 5 years.

Authors found that ABPM is a better predictor of cardiovascular deaths or deaths from any cause, compared to clinic BP measurements. These results are in accordance with recent American Heart Association guidelines published in December 2017 and common sense approach that more data is better then less in reaching statistically meaningful results.

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SPRINT trial: customized blood pressure goals

SPRINT trial: customized blood pressure goals

Further sub-analysis of SPRINT trial uncovers the point of balance between treatment benefit and harm in the setting of cardiovascular illness. The higher the baseline CVD risk, the more benefit is achieved by intensive blood pressure therapy; while the lower the risk, the higher the harm. Baseline cardiovascular status is obtained by the 10 year ASCVD risk estimator, which can be found online here.


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BMI vs. CVD contradiction

BMI vs. CVD contradiction

The study observes that higher BMI is associated with higher cardiovascular mortality and morbidity. On the contrary, it is intriguing to see that CVD longevity is prolonged in adults with elevated BMI (>25) compare to those with normal BMI (19-25). A speculative explanation could be that once cardiovascular illness has been established, the high BMI-induced damage is irreversible and subsequently somewhat protective. Future research will clarify the molecular mechanisms of these observations.

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Atrial fibrillation in aging adults

Atrial fibrillation in aging adults

This is an important study evaluating the associative factors and natural history of atrial fibrillation. Until age 90, men are at higher risk of developing A.Fib compared to women. Tall women, and overweight and dyslipidemic men are more likely to experience it than their counterparts. Lifetime risk for Atrial fibrillation high, more than 30%. It increases the mortality rate by 3.5 fold in both genders. Subjects were followed for about 13 years.

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Systolic blood pressure in heart failure

Systolic blood pressure in heart failure

The study finds that low systolic blood pressure in the hospital is associated with increased re-hospitalization and mortality rates among patients with heart failure but preserved ejection fraction (EF>50%). Mortality disadvantage was seen as far out as in 1 month, 1 year and 2.6 years after discharge in those with hospital systolic BP < 120 mmHg. These results could change hospitalists' approach to blood pressure management in heart failure.

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A deeper look of how jardiance prevents cardiovascular disease

A deeper look of how jardiance prevents cardiovascular disease

Authors find that hemodynamic changes are the main contributors to jardiance-induced cardiovascular benefits. Plasma volume contraction and hematocrit rise appear to be key mediators. Reductions in glycemia and uricemia also help in the process. The SGLT-2 inhibitor saga is evolving, and will continue for many years to come.

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Hyperthyroid and ventricular fibrillations

Hyperthyroid and ventricular fibrillations

This case shows a positive correlation between thyroid levels and J-wave amplitude in a patient experiencing ventricular fibrillations. Pronounced J-waves in multiple EKG leads can predict lethal arrhythmias, thus early diagnosis and treatment are necessary. More research would be needed however to clarify or solidify the cause-effect dance between hyperthyroidism and elevated J-waves. 

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Cardiovascular benefits of GLP-1 agonists

Cardiovascular benefits of GLP-1 agonists

This meta-analysis of four major clinical trials (ELIXA, LEADER, SUSTAIN 6, EXSCEL) reveals safety of GLP-1 agonists, bur more importantly their cardiovascular benefits on mortality, myocardial infarction and stroke in adults with type 2 diabetes. 

The next natural step would be the quest for oral version of GLP-1 agonist given its positive profile on appetite, glucagon, insulin, glucose metabolism, proteinuria and cardiovascular system.

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Jardiance is also beneficial in mild kidney disease

Jardiance is also beneficial in mild kidney disease

Patients with type 2 diabetes, cardiovascular illness and kidney disease were randomized to receive jardiance or placebo. Baseline renal parameters were eGFR 30-60 and albuminuria of >300 mg/day.

Study found that jardiance improved outcomes significantly: all-cause mortality by 24%, cardiovascular death by 29%, all-cause hospitalization by 19%, and heart failure hospitalization by 39%.

Findings are overall consistent with prior clinical trial results.

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Primary hyperaldosteronism amplifies cardio-metabolic anomalies

Primary hyperaldosteronism amplifies cardio-metabolic anomalies

Important to diagnose primary hyperaldosteronism early as a cause of high blood pressure since patients are even at a higher risk for: stroke, coronary artery disease, atrial fibrillation, heart failure, left ventricular hypertrophy, diabetes and metabolic syndrome.

Risks were evenly high for both aldosterone-producing adenoma and bilateral adrenal hyperplasia. About 13,000 patients were followed for 9 years.

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​​​​​​​Precision is everything, even in acute MI

​​​​​​​Precision is everything, even in acute MI

Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only, than among those who underwent immediate multivessel PCI.

NEJM

Calcium score is important in adults with diabetes and metabolic syndrome

Calcium score is important in adults with diabetes and metabolic syndrome

The MESA study uncovered the significance of coronary artery calcium (CAC) score in predicting coronary events among adults with diabetes and metabolic syndrome. About 7,000 individuals without baseline CVD were followed for 11 years.

Authors found that calcium score was more important than severity or duration of diabetes in identifying patients at higher risk for coronary heart disease. CAC score was equally useful in those with metabolic syndrome and without diabetes. 

In the future I anticipate CAC score to be incorporated in the ASCVD risk calculator as an independent predictor. Such a calculator is provided by the American College of Cardiology and American Heart Association (click here). It estimates the risk of an ASCVD event in 10 years based on person's age, gender, race, cholesterol, blood pressure and history of diabetes and smoking.

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New paradigm: how to treat diabetes in the context of cardiovascular illness

New paradigm: how to treat diabetes in the context of cardiovascular illness

Based on EMPAREG, LEADER, SUSTAIN, CANVAS and IRIS trials, authors propose a new treatment model for persons with type 2 diabetes and cardiovascular disease. The algorithm is listed below.

Metformin is still first-line therapy for those with A1c > 7.0%. SGLT2-inhibitors; jardiance or invokana should be prescribed next for adults with heart failure or cardiac atherosclerosis. However, patients with history of stroke or TIA should receive pioglitazone after metformin. GLP-1 agonists; victoza, saxenda or semaglutide are listed as third-line agents in this protocol.

The proposed paradigm is reasonable; however, cost, health insurance decree, side effects, added benefits, kidney function, route of administration, drug frequency and patient's preference also need to be considered.

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Fish oil and cardiovascular mortality

Fish oil and cardiovascular mortality

Omega 3 fatty acids, mainly eicosapentaenoic and docosahexaenoic acids, seem to lower cardiac death by 8%. This meta-analysis includes 14 randomized clinical trials with a total of 72,000 subjects. 

Further benefits (13-29% death reduction) were seen in adults utilizing higher doses of omega 3 (> 1 gram per day) and in those with higher baseline cardiovascular risk; elevated triglycerides (>150 mg/dL), LDL-cholesterol (>130 mg/dL) and non-statin users.

Important to note that these results are to some degree in accordance with the recent Science Advisory from the American Heart Association published in March 2017, suggesting the use of omega three for secondary prevention of coronary heart disease, heart failure and sudden cardiac death.

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How the diabetes drug protects the heart

How the diabetes drug protects the heart

EMPA-REG trial found that jardiance, an inhibitor of sodium-glucose cotransporter, lowered the risk of heart failure in patients with diabetes. Many pathways have been proposed for such benefits.

Authors propose that reduced activity of the sodium-hydrogen exchanger in the heart and kidneys is the main inciting factor in preventing heart failure. Decreased blood pressure, body weight, fluid retention, and kidney function preservation also play a role. 

Further research would be needed to clarify the molecular, cellular, metabolic, and hemodynamic intricacies of the SGLT2-inhibitor as an armour of the heart.

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A massive trial on a new cholesterol medication: CETP inhibitor

A massive trial on a new cholesterol medication: CETP inhibitor

Cholesteryl ester transfer protein (CETP) is an important component of lipid metabolism. It helps exchange triglycerides and cholesterol between HDL and atherogenic particles (LDL, IDL and VLDL). Reduction or inhibition of CETP leads directly to both higher HDL-cholesterol and lower atherogenic particle concetrations. In principle, these lipid profile modifications are expected to reduce cardiovascular outcomes. 

To date, three CETP inhibitors (torcetrapib, dalcetrapib, evacetrapib) tested in clinical trials were either not effective in reducing CV outcomes or caused major adverse events. The current study published in NEJM September 2107 paints a different picture: anacetrapib 100 mg once daily lowered coronary events by 10% in patients with established CVD being treated with high intensity statin (atorvastatin/lipitor). Authors attribute these benefits primarily to non-HDL reduction of 17 mg/dL. Although HDL increased by 43 mg/dL, it is not considered causative or therapeutic.

Some unforeseen outcomes with anacetrapib were the subtle increase in systolic blood pressure of 0.7 mmHg, slight decrease in kidney function and lower incidence of new-onset type 2 diabetes. 

Study results are of major significance for several reasons. Some adults with very high baseline CVD risk (ex. prior myocardial infarction) still have residual chance for more coronary events even when receiving a high intensity statin such as atrovastatin or rosuvastatin. Thus an add-on medication like  anacetrapib could be useful. Importantly, results were derived from a massive amount of data involving ~30,000 participants over a 4 year period. Participants' baseline LDL-cholesterol (~60) and non-HDL-cholesterol (~90) were well controlled and balanced across study groups.

Given poor outcomes from other sister medications, I suspect more research is needed to fully elucidate the benefit/harm ratio for CETP inhibitors, and particularly for anacetrapib.

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Heart bypass surgery is better than PCI in type 1 diabetes

Heart bypass surgery is better than PCI in type 1 diabetes

The study evaluated clinical outcomes in patients with type 1 diabetes and multi-vessel cardiac disease. Patients received either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). A group of 2,500 individuals were followed for about 10 years. 

After adjustment for various confounders, authors found that type 1 diabetes patients who underwent CABG experienced significantly lower outcomes in repeat revascularization, myocardial infarction, coronary heart disease and CV death, compared to those who received PCI.

When invasive therapy is indicated, it is reasonable to conclude that type 1 diabetics with multi-vessel heart disease should undergo CABG rather than PCI.

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