PracticeUpdate: Diabetes

EXPERT OPINION 17

Hypertension and Lipids in Diabetic Patients With CVD Interview with Benjamin Morgan Scirica MD Dr. Scirica is a Cardiologist and

Director of Innovation in the Cardiovascular Division of Brigham and Women’s Hospital, Associate Professor of Medicine at Harvard Medical School, and Senior Investigator of the TIMI Study Group in Boston, Massachusetts.

Considering recent data showing the LDL-lowering effect of PCSK9 inhibitor evolocumab without a concomitant increase in dysglycemia, how should lipid-lowering be approached in high-risk patients? Dr. Scirica: So, all patients with diabetes should be on lipid-lowering therapy and in most cases, it should be intensive lipid-lowering therapy because the car- diovascular risk of these patients is so high. There has been a well described observation in the statin

therapies that high dose statins in particular may worsen glycemic indices and actually make people develop diabetes a little bit ear- lier than they would’ve beforehand. And it’s led to some concern, “Do statins induce diabetes and is that bad?” My short answer for that is that you still reduce cardiovascular events, including cardiovascular death with statins, so even if it were to increase glucose that would still be greatly outweighed by the cardiovas- cular benefit. The PCSK9 inhibitors, which were by a completely different mech- anism and result in LDL reductions even greater than the statins have not been associated with increases in glucose or any dysg- lycemia, suggesting that there is an ability to disconnect the LDL lowering with glucose. And it’s fortunate that that’s seen with the PCSK9 inhibitors because diabetic patients are probably one patient group that is likely to benefit even more from an absolute stand- point from PCSK9 inhibition than other populations. A recent study comparing the risk of CVD and mortality in subgroups of prediabetes defined by fasting plasma glucose, 2-hour plasma glucose and HbA1C showed that prediabetes by HbA1C criteria was associated with a substantially higher risk of CVD and mortality. How should these patients be approached from a CVD risk stratification and primary prevention perspective? Dr. Scirica: We use a fairly artificial cut point to define diabetes, meaning a HbA1c > 6.5, fasting plasma glucose > 125, or a 2-hour glucose tolerance test > 200. That does not mean that having a HbA1c of 6.3 or 6.4 is normal. The truth is dysglycemia starts much earlier than that and it is a continuum of risks. And we’ve decided that 6.5 is the magic number, but patients in the pre-diabetes zone, which is 5.7 to 6.4%, still are at increased cardiovascular risk compared to those patients who don’t have any evidence of dysglycemia and they deserve several things.

They certainly deserve to have risk stratification. They need their risk factors for cardiovascular disease, like lipids and hypertension well controlled, and they need therapy – both lifestyle and diet as well as medications when indicated – to try to prevent worsening dysglycemia. And so, if you can prevent somebody from getting worse dysglycemia you’re going to make them better for a lot of reasons. That is a group that is even larger than what is already a large diabetic population and one where if we can get inter- ventions to them we can actually change the entire course and trajectory of diabetes and improve outcomes not just now, but in 10, 20 years forward. You have written about blood pressure and CV outcomes in diabetic patients with high CV risk. What are some of the associations between low diastolic BP and CV outcomes in this group of patients? Dr. Scirica: Blood pressure control remains controversial not only in the general population, but also in patients with diabetes. We’ve found in our studies, and similar to other studies, that you can perhaps get too low in terms of blood pressure in particular for the diastolic blood pressure. And we’ve seen that an association between low diastolic blood pressure and elevated levels of car- diac troponin suggesting that there may be a small amount of myocardial injury that is associated with the low diastolic blood pressure. We’re not sure exactly why that it is but is probably because the diastolic blood pressure is important for coronary profusion. And if you decrease the diastolic blood pressure too low you may induce low-level ischemia. So, I think the take-home is that we still need to do better at controlling blood pressure in patients with diabetes in particular focusing on the systolic blood pressure. But I think we do have to be conscious that we don’t lower the diastolic blood pressure too low. www.practiceupdate.com/c/65302

VOL. 2 • NO. 3 • 2018