Shireen: Dr. Rishi Rikhi is a cardiovascular medicine fellow at Atrium Health Wake Forest Baptist, with a passion for heart disease prevention and public health research. He is interested in several aspects of primary prevention, including lipids, diet, and physical activity. His current projects focus on lipoprotein (a) cardiovascular disease risk. Welcome, Dr. Rikhi. 

Dr. Rikhi: Thank you so much, Shireen. It’s a pleasure to be here. I’m really happy to be invited. Thank you. 

Shireen: And it’s a pleasure having you on and Dr. Ricky, so diving right in, tell us first a little bit just about yourself. What really inspired you to pursue a career in cardiovascular medicine? 

Dr Rikhi: Yeah, well I, you know, I’ve always had a really strong passion for, you know, fitness, nutrition since a young age. And as I got older, I became fascinated with how, you know, we can modify certain risk factors in our lives to live healthier lives. And in medical school, I started working as a personal trainer and was able to seek firsthand the impact of exercise and primary prevention of cardiovascular disease. These experiences, you know, led me to follow my passion to become a preventative cardiologist, especially knowing that cardiovascular disease is the leading cause of death and disability worldwide.

Shireen: And then can you talk to us a little bit and just, you know, from your bio even talking about prevention, what is primary prevention for cardiovascular disease? 

Dr. Rikhi: Yeah, absolutely. So primary prevention refers to individuals who have never had a heart attack or stroke before. And so these individuals can often have risk factors for cardiovascular disease, such as hypertension, high cholesterol, smoking, diabetes, and obesity. And if these are modified, it can lower the risk of cardiovascular disease. And this is in the comparison to secondary prevention of cardiovascular disease where these individuals have experienced a heart attack or stroke and they still benefit from favored and measures in order to reduce a future cardiovascular event.

Shireen: Mm-hmm. And so, Dr. Ricky, you did a study about the Association of Lipoprotein (A), so first, tell us what that is. So you did a, a study on this about the Association of Lipoprotein (A) and hypertension in the prevention of cardiovascular disease. Can you also give us an overview of the purpose of the study and what question you and your team really wanted to explore through this?

Dr. Rikhi: Yeah, so Lipoprotein (A) is not, is another atherogenic lipid similar to LDL, which is commonly known as the bad cholesterol. What’s special about Lipoprotein (A) is that it has an additional protein component called apo lipoprotein A, and what that causes is a lot of heightened inflammation, antifibrotic, and prothrombotic properties. And so not only do you have the increase pro pathogenicity, which means more likely to form plaque from the LDL component, but you also have all these other properties as well from LP little A. And so there’s not a lot of information out there regarding this association between hypertension and Lipoprotein (A). So what we wanted to do is investigate how these two cardiovascular disease risk factors are associated with each other. 

Shireen: Perfect. And then can you also share with us what hypertension in particular is and what factors lead to hypertension? 

Dr. Rikhi: Yeah. Well, our arteries are our blood vessels that carry, you know, blood to our organs and deliver oxygen to them. And we need a certain amount of pressure in order to deliver this blood to our organs, and so blood pressure is extremely important, however, when blood pressure becomes too high, that’s known as hypertension, and you can kind of think about it as your body’s being exposed to a higher level of pressure, but pretty much on a constant and daily basis.

And, you know, we often get our blood pressure measured in the clinic, in the office, and we can do this at home too now with home monitoring and we can also get this checked at the pharmacy. The blood pressure is a reading. It has a top number and a bottom number. Top number is the systolic blood pressure, and that’s really just the blood pressure when the heart’s contracting. And then the bottom number is the diastolic blood pressure and that really refers to the blood pressure when the heart’s relaxing. The major risk factors for hypertension are really very similar to the risk factors of other cardiovascular diseases and those include tobacco use, alcohol use, obesity, poor nutrition, and physical activity.

Another very important risk factor is age, which is a non-modifiable risk factor for hypertension. In fact, you know, as we all age, approximately 90% of all of us will develop hypertension eventually as we aged. And then it used to actually be called essential hypertension because it was thought that as we aged we needed this increased blood pressure and it was essential for us as we got older, but it’s actually a misnomer ‘cause there’s actually nothing essential about the having elevated blood pressure that is too high. And even at an older age, we’ve seen studies that controlling blood pressure is beneficial at all ages. 

Shireen: And so when we’re speaking about hypertension in particular with a high blood pressure, and I didn’t know the number was 90%, so that’s, that’s quite a big number. What are the treatments for hypertension? 

Dr. Rikhi: Well, I think the best and first treatment that you know, no matter what level of your blood pressure is, should be, you know, lifestyle changes. And so those can be things like exercise and nutrition. Studies have shown that exercise can reduce systolic blood pressure by about five to 10 points, and diastolic blood pressure about five points.

And, you know, the typical recommendation is about 150 minutes of moderate aerobic activity a week, or 75 minutes of vigorous aerobic activity a week. And I think the main, the best thing is really just to have some type of activity in the day that is, that is something that can be consistent and is something that is adaptable to your lifestyle. So walking is something that has tremendous benefits and it’s something that, you know, even 30 minutes a day of walking can be very beneficial. And if, you know, smart watches and Fitbits are also different methods of tracking steps and, you know, getting about 10,000 steps is another way to ensure that you’re getting enough aerobic activity.

And I think, you know, as we get more and more information about exercise and blood pressure, we’re starting to realize the impact of anaerobic activity and weightlifting and how beneficial that is for lowering blood pressure and overall cardiovascular disease health. So that’s something that shouldn’t be forgotten as well.

And diet is another very important thing regarding blood pressure and controlling hypertension and a strong diet, exercise can be beneficial as taking a medication for blood pressure use. And the main diet, you know, recommendations are to really, you know, limit sodium. And this doesn’t just mean, you know, limit the amount of sodium that we’re putting on our food in terms of added sodium, but really limiting where, what we’re buying in terms of that have high sodium, snd so these are really processed foods, canned foods, oftentimes, you know, there is the convenience aspect of, of canned food, but frozen alternatives are often much less than sodium, so, for instance, frozen broccoli or frozen vegetables, frozen berries are gonna be pretty low in sodium compared to the canned alternatives.

The other recent studies that have come out with nutrition have shown that plant-based protein, and that means things like lentils, other legumes and tofu are very beneficial in lowering cardiovascular health and also blood pressure. And in terms of meat, the one that has been shown to be associated with elevated blood pressure is are typically the red meat.

So those are probably the ones to limit most. And so those are what I like to focus on at first with blood pressure. We typically like to have a blood pressure goal of less than one 20 over 80, blood pressure above one 30 systolic, which is top number or above 80 diastolic, which is the bottom number is considered a diagnosis of hypertension as long as you have that on two separate readings and so, you know, I think it’s perfectly okay to start with lifestyle changes. 

If afterwards, you know, you’re still having elevated blood pressure, the next treatment would be pharmacological therapy. And we have multiple different medications and we really debate treatment based on, you know, other coexisting conditions such as coronary artery disease, heart failure, kidney disease. And these treatments include, you know, calcium channel blockers, ace inhibitors angiotensin receptor blockers, and a variety of other types of medications as well. 

Shireen: Interesting. And I, and I do wanna switch gears back over to Lipoproteins and what we were talking about there. Can you explain to our listeners, and you mentioned the similarity to LDL, but can you explain to our listeners exactly what Lipoprotein (A) is and then also how it differs from other lipoproteins inside our body?

Dr. Rikhi: Yeah, absolutely. So I think it would be helpful to talk a little bit about LDL first, so LDL is an apo lipoprotein B lipid, and it is studied very well and there’s multiple different showing that. Not only is LDL independently associated with atherosclerotic cardiovascular disease, but it’s causally associated as well.

And so most, all our treatments are really focused on lowering LDL in terms of lowering not only LDL cholesterol, but lowering overall global cardiovascular disease risk and we typically do this with statin therapy. Now what we have seen is that people who do have a controlled ldl, so they might have a normal LDL but are still having cardiovascular disease events such as heart attacks and strokes, and so there’s something else going on, some residual risk that’s still present.

And so we’ve, over the last couple decades, you know, there’s been a lot of interest in Lipoprotein (A), which is a lipid that is largely genetically determined and is very similar in appearance to LDL with the apo B component, but as I had mentioned, it has another component, which is the APO A. And so not only is Lipoprotein (A) similar in that it increases plaque formation like LDL does, but it also causes a lot of inflammation and it causes increase likeliness for clot formation as well.

And so we do know that as plaques, you know, heart attacks really don’t happen from plaques growing consistently over a time period, but they really happen from plaque rupture. And so these unstable plaques are really what’s causing these heart attacks and strokes and a lot of these cardiovascular disease events.

And so one of the benefits of statins is that they stabilize these plaques as well, that if you have a lot of inflammation in the body, These can destabilize the plaque. And so that’s something that is very concerning about Lipoprotein (A) 

As I mentioned, you know, this is something that is genetically determined, so we, there have been studies and unfortunately, you know, diet and exercise, which have been shown to be very helpful for controlling low density and lipoprotein cholesterol, the LDL with a bad cholesterol has actually no effect on Lipoprotein (A) and we know it largely genetically determined. 

Shireen: That’s quite fascinating. So this, this whole time when we’re sort of emphasizing lifestyle change is just part of this story because there’s also like this genetic factor at play as well, which is associated with the Lipoprotein (A). 

Dr. Rikhi: Absolutely. Yeah. So there’s, there’s a genetic component and you know, unfortunately, you know, lifestyle changes do not impact Lipoprotein (A), but we do know that people who have elevated Lipoprotein (A) are at increased risk for cardiovascular disease events even when their LDL is low, and even if their LDL is high, and whether this be primary prevention or secondary prevention. So there’s been enough evidence to know that those who have elevated Lipoprotein (A) are at increased risk. So while there’s no direct treatment medical therapy right now for Lipoprotein (A), those individuals should be aggressively treated to mitigate cardiovascular disease risk, such as statin therapy.

There are and, and there are very promising drugs in trial right now that have been shown to lower Lipoprotein (A) over 90%, which is quite impressive. And these are being presented at some lake breaking trials. And next year we should actually have some more information about this.

Shireen:  That’s interesting. And so essentially in a, in a case where there is elevated Lipoprotein (A) in particular, so the options as it stands right now are statins and then these particular medications. Anything else that an individual can do for elevated Lipoprotein (A)?  

Dr. Rikhi: One of the ways, you know, statins. Work is by, you know, cholesterol is really synthesized in the liver. And so statins inhibit one of the enzymes in the cholesterol synthesis pathway. And when it does that, the liver starts to express more LDL receptors on the liver, and that allows for the LDL particles to get cleared out of this circulation. And that lowers LDL. And it’s not actually clear why, but statins actually increase l Lipoprotein (A) by about 10% and it’s not really clear why, and it that that level of risk of increase is not enough to justify not using a statin therapy.

There’s other therapies out there PCSK9 inhibitors. And what these medications are are PCSK9 is a protein that is secreted from the liver and it bind to those LDL receptors and it really prevents it from being recycled back up and being reused for LDL clearance. And we do know that PCSK9 inhibitors are able to lower LP little A by about 25%.

So while it’s not, you know, FDA approved for Lipoprotein (A) reduction, this is something definitely that’s promising. We will need those therapies that have the ability to lower LP little A by much greater because there’s people who have Lipoprotein (A) levels that are much, much higher and we usually use the threshold of about 50 milligrams per deciliter as increased risk. And so you can imagine someone who has a Lipoprotein (A) of 200, you know, lower by 25% just won’t be enough. 

Shireen: I see. And then speaking of that, can you share with us from your study in particular, what association did you and your team really find between Lipoprotein (A), hypertension, and then cardiovascular health?

Dr. Rihki: Yeah, so, you know, our study we used MESA, which is the multiethnic study of atherosclerosis. And so our population included 6,674 individuals and all these individuals were free of cardiovascular disease at baseline. So this is a primary prevention cohort. And we followed these individuals for about 14 years, and what we found was that LP little a significantly modified the association of hypertension in incident cardiovascular disease.

So when we look at the overall population we saw, we looked at survival populations over those 14 years, and we looked at, specifically looked at hypertension by itself. And hypertension is such a strong risk factor for cardiovascular disease that you can see divergence in the people who have hypertension versus who do not have hypertension in less than one year.

It’s pretty impressive how strong of a risk factor and hypertension really is. And now when you look at Lipoprotein (A) by itself, It’s not as strong of a risk factor it seems like as hypertension, but we do see divergence between the groups who, the overall groups between those who have elevated Lipoprotein (A) and those who do not have elevated Lipoprotein (A). And that divergence happens by about year two. So it’s a little bit slower, but it still happens. And another thing to note is that this cohort is a very healthy primary prevention cohort. So the, you know, These results might be different in a more higher risk cohort or a secondary prevention cohort as well. So that’s what we kind of can see when we look at these two risk factors separately, hypertension and Lipoprotein (A). 

Now hypertension is the overall risk seems to be driven by hypertension, and when we look at both risk factors combined together, we can see that those who do not have hypertension having elevated Lipoprotein (A) do not really matter too much. But, when you do have hypertension, Lipoprotein (A) did have quite a big impact and statistically significantly increased cardiovascular disease risk in the population. 

Shireen: So that is fascinating. Dr. Rihki. So from what you’re mentioning here, it’s really to make the case that when it comes to hypertension, then there is a lot that we can have control around, starting up with lifestyle changes, physical activity, dietary changes, all those changes that we can make and really be able to influence that hypertension that can essentially lower that risk of the cardiovascular event. Can you also help us understand a little bit more about, then, what does it mean to incorporate those changes to impact hypertension in particular?

Dr. Rikhi: Yeah, so definitely, you know, this study does suggest that those with hypertension and elevated Lipoprotein (A) are at increased cardiovascular disease risk, and so, you know these individuals, I would support having more aggressive interventions, more aggressive lifestyle interventions, whether that be diet, exercise, and also a favor earlier treatment 

Now, this is just one study and it is a large study of 6,000 participants, but these studies definitely need to be replicated in other cohorts as well to better understand the mechanistic association between Lipoprotein (A) and hypertension. But from what we can see, does support more aggressive measures for those who have hypertension and elevated Lipoprotein (A). 

Shireen: And we’ve been talking about cardiovascular disease a little bit more broadly, can you share with us what specific cardiovascular diseases are really associated with this high levels of Lipoprotein (A) and then hypertension like we were talking about, and then what are some ways that people can manage these levels? 

Dr. Rikhi: Yeah. So Lipoprotein (A) is associated most strongly with coronary heart disease. So these would be things like having a heart attack, like a myocardial infarction. Lipoprotein (A) is also strongly associated with peripheral artery disease, and so these are, this is basically very similar to having disease in the coronary arteries are just in the blood vessels in the legs, and so, oftentimes these patients will present with pain, with walking and feel better when they rest.

So it’s very similar to, you know, people presenting with chest pain where they’ll have chest pain with exertion and then they’ll get better with rest and there is some evidence not as strong for a Lipoprotein (A) and stroke as well. And so that’s something that is currently being studied more. 

The other association that’s pretty interesting about Lipoprotein (A) is Calcific aortic valve stenosis, which is one of the valves in the heart, the aortic valve, it can lead to a cystinosis, which is basically a narrowing of the valve, and that can lead to decreased blood flow for the rest of the body, and often we’ll need surgical replacement for that. And so we’re still understanding the kind of mechanisms behind Lipoprotein (A) and how it impacts aortic valve. Those are the main specific cardiovascular diseases that Lipoprotein (A) is associated with. 

Hypertensive pretension is associated with a whole variety of cardiovascular disease, so it doesn’t just affect the endothelium and coronary blood vessels are leading to myocardial infarction, heart attacks. I like to think about, you know, the heart is really pumping against the blood pressure and so the more the heart has to pump against the kind of more stronger it will get in a sense in terms of remodeling.

And so it’s like if you were to go bench press and you’re pushing a hundred pounds, and then suddenly you push are starting to push 200 pounds, your heart can get over time when it’s exposed to so much, it can atrophy, which basically it’s just like any other muscle in the body will get bigger and bigger.

And this is actually, you know, a bad thing over time because this type of remodeling can lead to heart failure. So we know that not only is hypertension associated with cornea heart disease, but associated with heart failure, and hypertension also plays a role with many other organs, not just the heart.

It affects the eyes that can lead to blindness, it affects the kidneys, it can lead to kidney damage. It’s a, it’s a very common reason for individuals to end up on dialysis. So, our blood flow goes through all our organs, and so when it’s elevated, it affects almost every single one of our organs and so controlling our blood pressure is one of the most important things we can do in our lives.

Shireen: Lovely, and real quickly before we let you go, Dr. Rihki specifically finds someone who wants to find out if I have elevated Lipoprotein (A) levels, where do I go to find that? 

Dr. Rikhi: Yeah. So right now, you know they’re being tested clinically. Most cardiologists are testing for prevention purposes, and some people, their primary care doctors and internal medicine clinics will also be checking.

Sometimes there will be a send out lab, and so it might take a little bit longer to get the result, but it is not something that is easily accessible and it’s quite affordable to get it checked. And so oftentimes a referral to cardiology is all you mean. 

Shireen:I see. Okay. Lovely. That is certainly good to know and to our listeners who are interested in doing that, that is, that seems like something you can get at your next PTP appointment or your cardiovascular cardiologist appointment.

Dr. Rikhi: Absolutely. 

Shireen: Lovely. With that, Dr. Rihki, thank you so very much for your time and for hanging back a couple extra minutes here. Please tell us how can we connect with you and nerd out more about this stuff? How can we learn more about the work that you’re doing? 

Dr. Rikhi: I would love to connect at any time, any, if anyone’s interested in learning more about Lipoprotein (A) or hypertension. I have, I’m on Twitter and also my email, it’s rrikhi@wakehealth.edu. And so if anyone has any questions, please email me and would love to get back to you. 

Shireen: With that, Dr. Rikhi, thank you so very much for your time and to our listeners out there, you know the drill, it’s that time in the episode where we tell you to head over to our social media and answer this quick question, what questions do you have about the relationship between lipoprotein a hypertension and cardiovascular disease that was not addressed in this episode?

So we definitely wanna do a follow up and get all your questions answered. Head over to our social media. Head over to our Facebook, Instagram @Yumlish. You can find us there. And again, find this podcast post and comment below to tell us what questions do you have again about the relationship between Lipoprotein (A), hypertension, cardiovascular disease that wasn’t quite addressed in this episode, and we’ll try to answer it in the comments below. Again, head over to our social media. Dr. Rihki, thank you so much. 

Dr. Rikhi: A pleasure. Thank you so much.

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