Cardiovascular

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.

GT

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.

GT

More evidence of Metformin benefits in early prediabetes

More evidence of Metformin benefits in early prediabetes

More good news for metformin. MET-REMODEL trial tested patients with known cardiovascular disease and insulin resistance, but without gross diabetes. Patients received metformin or placebo for 12 months.

Compared to the placebo group, subjects receiving metformin experienced the following improvements in 12 months: Less left ventricular mass index,  less LVM, lower systolic BP, decreased body weight and less oxidative stress.

Early start of metformin could be useful in adults with insulin resistance.  Long term side effects of metformin, however, need to be discussed thoroughly with patients.

GT

Addition of PCSK9 inhibitor Alirocumab further lowers CVD events.

Addition of PCSK9 inhibitor Alirocumab further lowers CVD events.

In ODYSSEY trial, the addition of PCSK9 inhibitor, Alirocumab to high-intensity statin further reduced cardiovascular events by 15% in patients with very-high baseline CVD risk (prior ACS) and elevated atherogenic cholesterol particles. Atherogenicity was defined by LDLc ≥70 mg/dL, non-HDLc ≥100 mg/dL, or Apo B ≥80 mg/dL.

About 19,000 patients with acute coronary syndrome 1-12 months prior to study initiation were followed for 3 years. The study target was final LDLc between 25-50 mg/dL. Similar to FOURIER 2017 results, ODYSSEY 2018 adds more evidence to the notion “the lower the LDLc, the lower ASCVD events”

GT

Risk factors control is also important in type 1 diabetes

Risk factors control is also important in type 1 diabetes


This major observational study shows that the tight control of risk factors is associated with much lower rates of cardiovascular events and total mortality in patient with type 1 diabetes. Such factors are hyperglycemia, systolic blood pressure, protein in the urine, and the “bad” cholesterol (A1c, sBP, McAlb, LDLc).

This association has already been seen in adults with type 2 diabetes. For a practitioner, this study calls for a tight control of the above risk factors in patients with type 1 diabetes as in those with type 2. A group of 30,000 DM1 individuals were followed for about 10 years

GT

Thyroid supplementation in heart failure

Thyroid supplementation in heart failure

This 5-year observational study shows that thyroid hormone supplementation increases major adverse cardiovascular events (MACE), cardiovascular death, and all-cause mortality in patients with heart failure. Indirectly, this is in accordance with the well-documented benefits of beta-adrenergic receptor blockade in persons with cardiac failure.

Clinically, in patients with concomitants hypothyroidism and heart failure, thyroid hormone supplementation should be started at a low dose, increased slowly, and aiming a higher TSH target than in general population.

GT

Vascepa (fish oil) reduces ischemic cardiovascular events in high risk patients

Vascepa (fish oil) reduces ischemic cardiovascular events in high risk patients

The current study is of a major clinical significance as it shows that EPA lowers ischemic cardiovascular events by 25% in high rick CVD patients who are already receiving statin therapy. The EPA treated patients, however, experienced more hospitalizations for atrial fibrillation and a higher propensity for serious bleeding than placebo. Findings are remarkable as they come from a major randomized clinical trial (IMPROVE IT). About 8,000 patients were followed for 5 years.

This outcome data is in accordance with established observation and notion that hypertriglyceridemia is an independent risk factor for cardiovascular disease, mainly via increased inflammation and concentration of the non-HDL cholesterol. Prior clinical studies have also shown that EPA lowers non-HDL cholesterol more than DHA.

Omega-3s, EPA and DHA, are two key ingredients of fish oil. A stable and pure form of EPA has been FDA approved for very high serum triglyceride >500 mg/dL since 2012. It is marketed under the brand-name vascepa. Lovaza, a mixture of EPA and DHA, has also been approved by FDA since 2004 for severe hypertriglyceridemia.

I anticipate that in the future NLA, ACC/AHA, AACE and ADA guidelines will reflect and incorporate the current findings of IMPROVE IT.

GT

Lipoprotein(a), Familial Hypercholesterolemia and CVD

Lipoprotein(a), Familial Hypercholesterolemia and CVD

Familial hypercholesterolemia (FH) has a high prevalence of cardiovascular morbidity and mortality, due to the lifelong cumulative exposure of high serum cholesterol levels.

The study finds that only a minority of patients are capable of achieving LDLc targets set by the European guidelines. About 25% of FH patients reach LDLc ≤100 mg/dL and only 8% of very high-risk CVD patients reach LDLc ≤70 mg/dL.

Importantly, those with high Lp(a) experienced twice as much CHD events than those with low Lp(a) levels. Specific drug development toward Lp(a) would be a breakthrough in helping patients with familial hypercholesterolemia.

A group of 714 FH adults were followed for about 11 years.

GT

Newer diabetes medications also help prevent heart and kidney disease

Newer diabetes medications also help prevent heart and kidney disease

About 80,000 diabetes patients were analyzed from 8 clinical trials.

Authors found that GLP1 agonists and SGLT2 inhibitors prevented cardiovascular events (MACE) equally by 14% in those with established CVD. However, both classes of medications did not appear to be effective in reducing MACE in adults with diabetes but without established CVD.

SGLT2 inhibitors showed superior results compared to GLP1 agonists in regard to preventing hospitalizations for heart failure or severe kidney disease progression, such as end-stage-renal disease or death.

If cost, side effects, drug interactions and contraindications allow, diabetes patients would greatly benefit from these therapies on three fronts; glucose control, heart and kidney disease prevention.

GT

Second line diabetes medication on the risk of CVD

Second line diabetes medication on the risk of CVD

Among patients with type 2 diabetes initiating second-line diabetes therapy, the short-term cardiovascular outcomes of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors were similar.

Higher cardiovascular risk was associated with use of sulfonylureas or basal insulin compared with newer drug classes.

Clinicians may consider prescribing GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors more routinely after metformin rather than sulfonylureas or basal insulin.

JAMA

Familial Hypercholesterolemia and CVD risk factors

Familial Hypercholesterolemia and CVD risk factors

Genetic inability to clear LDL-particles leads to familial hypercholesterolemia. Persistent high serum LDLc and total-cholesterol are major cumulative risk factors for premature cardiovascular disease.

The article identifies other independent risk factors contributing to CVD in these patients. Such factors are male sex, smoking, hypertension, diabetes, elevated Lp(a), and family history of CVD.

Obviously, the modifiable contributors; hypertension, smoking and diabetes need to be managed aggressively.

GT

Certified Lipidologist

Certified Lipidologist

I am pleased to announce that, as of October 2018, I am a certified clinical lipidologist, accredited by the American Board of Clinical Lipidology (ABCL). The role of the lipidologist is to diagnose, treat, and manage patients with elevated cholesterol or triglyceride levels. Currently, there are approximately 700 certified lipidologists in the U.S.

Dyslipidemia is a major public health concern. Elevated cholesterol levels, particularly what’s called the “bad” cholesterol (LDLc) or non-HDL cholesterol are major risk factors for atherosclerotic cardiovascular disease leading to heart attack and stroke. World Health Organization estimates that globally, 45% of people have elevated total cholesterol.

Dyslipidemia could be monogenic, polygenic or due to comorbidities such as metabolic syndrome, insulin resistance, diabetes mellitus, chronic kidney disease, nephrotic syndrome, weight gain, lack of exercise, or use of other medications.

According to ABCL, I am 1 of 3 physicians in the U.S. who is certified in all three specialties; endocrinology/diabetes, hypertension and dyslipidemia. This allows me to provide comprehensive and detailed care to endocrine patients, particularly those with diabetes.

GT

Mortality and CVD in patients with diabetes type 1 and type 2

Mortality and CVD in patients with diabetes type 1 and type 2

In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. 

Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls.

NEJM

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.

GT

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.

GT

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.

GT

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.


GT

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.

GT

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.

GT

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.

GT