Exercise and Blood Pressure; Maternal Occupation and Autism

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include digoxin for heart failure, thrombectomy for strokes in medium-sized vessels, impact of maternal occupation on autism risk in offspring, and exercise and 24-hour ambulatory blood pressure.

Program notes:

0:36 24-hour ambulatory blood pressure and exercise

1:36 Aerobic, combined, and high-intensity interval training helped

2:36 Some combined with other things known to be beneficial

2:54 Medium-sized vessel thrombectomy

3:54 Thrombectomy or medical management

4:54 Carefully selected patients benefit

5:55 About 50-60% end up with minimal impact

6:40 Digoxin as fifth pillar of congestive heart failure management

7:40 Does help avoid hospitalization

8:37 Maternal occupation and autism in offspring

9:35 Jobs held ever, before conception, and other periods

10:35 How to protect against exposure

11:30 Confine your employment?

12:13 End

Transcript:

Elizabeth: Can endovascular treatment for stroke be extended to medium-sized vessels?

Rick: Should digoxin be the fifth pillar of therapy in people with heart failure?

Elizabeth: Does mom’s occupation have anything to do with the development of autism in offspring?

Rick: And does exercise training affect 24-hour ambulatory blood pressure?

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, I am so interested in this idea of exercise and ambulatory 24-hour blood pressure. I think we should turn straight to The BMJ.

Rick: I didn’t realize it hadn’t been analyzed before. We recommend exercise for both the prevention and treatment of high blood pressure (hypertension), but that’s usually on the basis of office blood pressure measurements. The office blood pressure measurements aren’t nearly as good as ambulatory, 24-hour blood pressure in terms of predicting mortality and cardiovascular risk and overall health outcomes. Both resistance and aerobic training can reduce office blood pressure. How do they affect ambulatory blood pressure?

They looked at all the randomized controlled trials that evaluated the effects of exercise training conducted for 4 weeks or more and compared them with a control condition or another exercise modality with regard to 24-hour systolic and diastolic blood pressures. This is the first comprehensive network meta-analysis.

And they showed that aerobic, combined exercise, and high-intensity interval training all significantly reduced 24-hour blood pressure versus control. They weren’t able to discern that any particular exercise modality was better. But they did note that the evidence regarding resistance training and isometric training and nonconventional exercise modalities, things like yoga or just recreational activities, there’s not enough data to show whether they do have an effect.

Elizabeth: We have reported in the past that per this notion of resistance exercise, which of course we have touted as providing additional reductions in mortality if it’s combined with other forms of exercise, should become part of somebody’s regimen. We’ve also reported that there are transient increases in blood pressure as a result of doing resistance exercise. So, I, for one, would be very interested in something that would take a look at that in isolation.

Rick: I agree. Resistance or isometric exercise in isolation, and then also combined with aerobic exercise. Some of these studies combined aerobic exercise with other things known to be beneficial like diet, supplementation, behavioral counseling. Whether resistance exercise adds additional benefit or not isn’t really known and it needs to be studied.

Elizabeth: Let’s turn to the New England Journal of Medicine, and this is a look at whether endovascular treatment is helpful for people who suffer strokes in medium-sized vessels. And these are occlusive strokes or ischemic strokes.

We know, of course, that endovascular thrombectomy in large vessels has been shown to be really beneficial. And that, and the addition also of thrombolytic agents, has really helped to improve outcomes in the long haul when people have that type of stroke.

Well, what about the medium vessels? Let’s see if we can extend this therapy to that group of folks also. There’ve been a number of studies that have taken a look at that, and this is a study from China that have shown the previous studies that there really wasn’t much in the way of benefit.

In China, they decided to do this study at 48 centers where they had patients who were adults presenting within 24 hours after the onset of a moderate to severe stroke in a medium-sized vessel to have either thrombectomy plus clot-busting drugs, or just the clot-busting drugs alone. Their primary outcome was functional disability with a modified Rankin scale score at 90 days or death. They wanted to see does it make a difference if we treat these people with thrombectomy in addition to medical management.

So they had over 500, almost 600 patients, more or less half and half randomized into these two groups. Functional independence at 90 days was seen in just about 59% of the patients in the thrombectomy group and just about 47% of those in the control group, or the medical management alone. However, that was at the risk of symptomatic intracranial hemorrhage, which occurred in just shy of 5% in the thrombectomy group and in 2.2% in the control group; 90-day mortality was really more or less the same, 11% in the thrombectomy group, 10.2% in the medical management group.

These authors come to the conclusion that in carefully selected people — and clearly you need to do a bunch of imaging in order to find this out — who have a medium-vessel stroke, that some of them might be suitable for a thrombectomy, extending that treatment modality to a small number of patients.

Rick: In three previous studies of medium-sized blood vessels, thrombectomy wasn’t helpful. These patients were younger, so they had less comorbidities. They all had moderate to severe strokes and you’re more likely to get a benefit if your symptoms are more severe. Fewer people in this trial got thrombolytic therapy in addition to thrombectomy, as opposed to the United States, where about 70% do. Here, only about 35% did. You’re right, is that in carefully selected patients, those that are younger, those that are more likely to have more severe strokes, and those that are less likely to receive thrombolytic therapy may benefit from this.

Elizabeth: Yeah. I think that maybe is really an important part of that conclusion.

Rick: I guess the thing that I was surprised at, about 50-60% can end up with minimal residual disability with current treatment, whether that’s thrombectomy or other nonthrombectomy treatment.

Elizabeth: Well, I just want to note that the editorialist concludes that most patients with stroke due to medium-vessel occlusion will not benefit from endovascular thrombectomy, and further opines that patients with well-evolved infarcts simply do not benefit, and a small proportion may actually be harmed by reperfusion therapy.

Rick: Getting the artery open as quickly as possible, regardless of the technique, is really the most valuable thing to take away.

Elizabeth: Let us turn now to JAMA.

Rick: Should digoxin be the fifth pillar in the treatment of people with heart failure? People with heart failure whose left ventricular function is depressed, either mildly or more severely. The other four treatment arms include ACE inhibitors and mineralocorticoids, beta-blockers, and more recent SGLT2 inhibitors.

Digoxin has been around for centuries, and it fell out of favor because previous studies suggested that using digoxin in people with heart failure, either whether they’ve had rheumatic heart disease or some other heart disease, did not improve overall survival. But it did decrease the risk of heart failure hospitalizations.

What these investigators did was said let’s go back and take a look at the evidence for digoxin in large, randomized trials to see is it beneficial, and specifically with a composite endpoint of mortality and reduced heart failure hospitalizations.

In over 10,000 patients total, digoxin, in addition to routine baseline therapy, did reduce the composite endpoint of mortality and heart failure hospitalizations. It did it fairly safely. Only about 1% of individuals ended up with digoxin toxicity, where the medication needed to be stopped.

Elizabeth: Let’s note that there are two studies that are addressing this in JAMA this week. I guess one thing that is attractive to me about digoxin is we have so much experience with it.

Rick: Yeah. Again, decades, Elizabeth. Centuries, because it’s derived from the plant called foxglove, so it’s been around for a long period of time.

But it fell into disfavor because there is toxicity associated with it. Well, what these studies did was they looked at using low-dose digoxin. This suggests that decreasing hospitalizations, which is just as important to patients, by the way, it can be beneficial.

Elizabeth: So tell me about the paradigm that you’re going to adopt.

Rick: I think we can add this as a fifth pillar, and I want to specifically say in those that have reduced ejection fraction, especially in those that are at high risk for hospitalization or have recurrent hospitalizations already. It hasn’t been shown to be beneficial in those with heart failure with preserved ejection fraction.

Elizabeth: Let’s turn now back across the pond to The BMJ. What maternal factors might influence the development of autism in offspring?

The associations, of course, we know that’s a really important caveat between maternal occupational history and autism spectrum disorder. This study was done in Denmark, always persuasive since they followed their citizenry so closely from the moment of birth, and now sounding like, gosh, they’re even doing it before birth.

They got data for now — and here’s where their big data sets break down — they had 1,702 autism spectrum disorder cases in Denmark between 1973 and 2012. What they did was match each case with up to 100 population-based controls based on sex and birth year. And they also obtained the mother’s employment histories from their Danish Pension Fund Registry. They tested the associations between occupations held ever, 1 year before conception, during pregnancy, and during infancy. And they adjusted for the mother’s age, history of neuropsychiatric disorders, parity, and residential location.

They found that there was increased risk associated, after correcting for all these other factors, with mom’s employment in ground transportation, public administration, and in military and defense occupations. Even more interestingly, the impact of these was dependent upon the sex of the child. When the child was male, it was the toxicant exposure potentially as a result of the transportation occupations or the military and defense occupations, where the female children who were impacted, their moms were in this public administration — so part of the judicial system or whatever that they say were probably high-stress occupations. It’s unclear to me how you’re going to protect against a lot of these occupational exposures.

Rick: They looked at a number of different things, occupations that seem to be associated with autism. But when they apply what they call the false discovery rate, they were suddenly no longer associated. You have to correct for things in addition to occupation — particulate air matter, comorbidities of the mother or father. Does the mother have psychiatric or neuropsychiatric disease? As well as we’ve talked about the fact not only the incidence of autism appears to be increasing, but the diagnosis is.

And by the way, the results were kind of marginal. Well, this particular thing increased it by 10% or 15%. This may be by about 20%. The numbers were small. Although it’s interesting, and we do need to look for possible mechanisms, this is a bit of a stretch for me.

Elizabeth: I think that the differential between the male and female offspring and the specific occupations was curious. What do you say to women who are planning to have children? “Hey, you need to really confine your employment to areas that are non-stressful and don’t have any potential exposure to anything that might be toxic”?

Rick: Yeah. It’d be very difficult. And there were other things that were exposed to the environment or to toxins like air transportation, chemical processing industries, cleaning services. They weren’t associated. That makes me a little bit more skeptical.

Elizabeth: I absolutely agree.

On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.