Category: Preventive Cardiology

Cancer’s CVD Risks and SGLT2is’ Preventative Potential

Posted on by Jake Fishman

Better treatments have led to improved cancer survival rates, but new research reveals increased cardiovascular complications in survivors. However, another new study offers hope, suggesting that heart medications like SGLT2 inhibitors may help prevent cancer-related heart disease.

A new Cancer Journal study showed that older cancer survivors have far higher rates of cardiovascular events than their peers who never had cancer. The study analyzed 15,454 ASPREE trial participants (all ≥65yrs) who had no history of cancer, including 1,392 (9%) participants who were later diagnosed with cancer and didn’t have a history of CVD.

  • Those cancer survivors proved two-times more likely to develop CVD than participants who never had cancer (21 vs. 10 events per 1k person years).
  • Patients treated with chemotherapy had two-times higher CVD incidence, while surgically-treated patients had 56% lower CVD rates.
  • CVD risk was greatest soon after cancer diagnosis (potentially due to chemo), and remained elevated across the 4-year follow-up period.

The authors attributed cancer’s CVD risks to a range of factors, including chemotherapy’s already-established CVD risks, but also the two diseases’ shared risk factors (e.g. smoking) and cancer-induced risk factors (e.g. inflammation). They also called for more efforts to expand cardiovascular screening and management efforts among cancer patients.

Another well-timed JACC study suggests that SGLT2 inhibitors could help mitigate cancer treatments’ cardiovascular risks. The study retrospectively analyzed 17,350 cancer patients with type 2 diabetes undergoing chemotherapy with cardio-toxic effects, half of whom were taking SGLT2 inhibitors.

  • The SGLT2i-treated patients had a 24% lower risk of developing cancer therapy-related cardiac dysfunction, and a 19% reduction in heart failure exacerbations.
  • The SGLT2i group also had 33% lower risk of all-cause mortality and 7% lower risk of all-cause hospitalizations or ED visits.
  • A subgroup analysis also showed that SGLT2i patients had lower risk of cancer therapy–related cardiac dysfunction across the various classes of cancer therapies.

The Takeaway

The fact that a cancer diagnosis is often followed by cardiovascular events is one of the many harsh realities of the disease, but this new JAMA study suggests that some heart meds might be able to prevent cancer’s cardiovascular risks. More research is needed before we see increased use of preventative CVD meds among cancer patients, but studies like these seem like a solid first step.

Tirzepatide’s Prediabetes and Hypertension Impact

Posted on by Jake Fishman

It looks like we might be able to add prediabetes and hypertension to the growing list of conditions that Eli Lilly’s “weight loss drug” tirzepatide is able to treat, after new analysis of the SURMOUNT-1 trial showed significant reductions in blood pressure and diabetes progression.

  • Tizepatide (aka Mounjaro and Zepbound) is often referred to as a GLP-1, but uniquely activates both GIP and GLP-1 hormone receptors.
  • Tirzepatide has already gained FDA approval for type 2 diabetes and obesity, while achieving greater weight loss than Novo Nordisk’s semaglutide.

Although tirzepatide is already widely used to treat diabetes, analysis of 1,032 obese or overweight prediabetics in the SURMOUNT-1 trial showed a whopping 94% lower risk of progressing to type 2 diabetes with tirzepatide through 176 weeks. 

  • During the subsequent 17-week off-treatment period, the patients began to regain weight and showed some increases in type 2 diabetes progression, resulting in a 88% diabetes risk reduction after the off-period.

A separate analysis of the SURMOUNT-1 trial’s first 72 weeks showed that tirzepatide led to lasting blood pressure control among 2,539 non-diabetic overweight/obese adults, leading to 6.8 mm Hg systolic and 4.2 mm Hg diastolic net reductions (mostly occurring in first 24 weeks).

  • By the end of the trial, 58% of tirzepatide-takers had normal BP versus 35.2% of placebo-takers.
  • Notably, weight loss drove around 70% of the blood pressure reductions.

Although Lilly might not specifically seek approvals for hypertension or prediabetes, these studies add to the growing body of evidence that tirzepatide’s impact goes far beyond weight loss and diabetes.

That’s a lot of future possibilities for a drug that generated $4.35B in the second quarter alone – despite supply constraints, limited payor coverage, and fierce competition from Novo Nordisk’s semaglutide.

The Takeaway

Tirzepatide was already one of the hottest drugs in the world, and these studies suggest that weight loss and diabetes care could prove to be just one part of its massive impact, especially when you consider that 98 million American adults are prediabetic and 120 million have high blood pressure.

New Calculations Could Slash Statin-Eligible Population

Posted on by Jake Fishman

A JAMA paper suggests that if the CVD guidelines adopt the AHA’s new PREVENT cardiovascular risk equations, it might slash the US’s eligible preventive statin user population by nearly 40%.

In November 2023 the AHA launched the PREVENT risk equations, which take into account a wider range of cardiovascular, kidney, and metabolic health measures to estimate 10- and 30-year risks of heart attack, stroke, and heart failure. 

  • The new equations notably added sex-specific risks and cardiovascular-kidney-metabolic syndrome metrics, while eliminating race since it’s not a biological factor.
  • The PREVENT calculator also represented a big change from 2013’s Pooled Cohort Equation (PCE), which was released before many CKM treatments were available, and faced criticism for overestimating CVD risks.

To evaluate PREVENT’s impact, the researchers applied the PREVENT and PCE equations to 3,785 adults aged 40 to 75 years without known ASCVD, 20.7% of whom currently take statins…

  • Patients had far lower estimated 10-year ASCVD risks with the PREVENT equations compared to the PCEs (4.3% vs. 8%).
  • The PREVENT equations’ estimated risks were lower across all age, sex, and racial subgroups.
  • PREVENT’s risk reductions were greatest among Black adults (5.1% vs. 10.9%) and people between 70 and 75 years (10.2% vs. 22.8%).
  • The PREVENT equations reclassified very few patients as higher risk for ASCVD, and most were classified to lower risk groups.

Add that all together, and transitioning to the PREVENT equations could reduce the number of Americans who meet the criteria for primary prevention statin therapy from 45.4M to 28.3M, while allowing 4.1M adults who are currently taking statins to get off their meds. 

The PREVENT equations aren’t included in the CVD guidelines yet, but their addition is expected by many, and the AHA has already launched a PREVENT calculator that’s intended for clinician use.

The Takeaway

There’s a good chance that the new PREVENT equations will have a major impact on patient care, reducing the number of low-risk patients who are prescribed statins, while hopefully increasing statin adherence among the highest-risk patients.

Preventive Statins Safe & Effective in Older Patients

Posted on by Jake Fishman

There is little consensus on whether or when to use statins for primary CVD prevention in older patients, but a new study in the Annals of Internal Medicine provides compelling evidence for expanding statin use in this population. 

The researchers analyzed matched pairs of statin and non-statin users without pre-existing CVD in the 60-74 (73,427 pairs), 75-84 (21,340 pairs), and 85+ (2,695 pairs) age groups using EHR data from the Hong Kong Health Authority.

Over five years, they found that statin use reduced:

  • Composite CVD events (MI, heart failure, or stroke) by 11%, 6%, and 15% in the three age groups.
  • Composite CVD events by 23%, 21%, and 35%, among patients who adhered to their statin treatments.
  • CVD event risks by 1.2% within the 75-84 age group, and 4.4% in the 85+ age group.
  • CVD event risks by 5% and 12.5%, among patients who adhered to their statin treatments.

Statins also didn’t significantly increase the patients’ myopathy and liver dysfunction risks, addressing one of the main arguments against initiating statins in older patients

In other words, this data suggests that preventative statin use has significant benefits among older patients, without significant risks.

The Takeaway

Few would argue against statins’ cardiovascular benefits, and most would agree that cardiovascular burdens are increasing in older populations, but many older people who might qualify for preventive statins still aren’t taking the drugs. This study might not be an RCT, but its results certainly support steering more of those at-risk older patients towards primary prevention statin therapy.

America’s CKM Syndrome Problem

Posted on by Jake Fishman

A new JAMA study revealed that a shocking 90% of US adults are at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome, underscoring the need for preventative action before we face a wave of CKM-related heart disease.

  • Officially published by the AHA six months ago, CKM syndrome defines the connections and risks associated with obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease.

The researchers analyzed 2011-2020 NHANES survey results and laboratory measurements from 10,762 nationally representative US adults (47.3yr avg. age, 51.8% women, 64.4% White) to assess their CKM stages, finding the following breakdown:

  • Stage 0 (no risk factors) – 10.6%
  • Stage 1 (overweight, prediabetes) – 25.9%
  • Stage 2 (metabolic risk factors like hypertension, diabetes, CKD) – 49%
  • Stage 3 (kidney disease or high cardiovascular risks) – 5.4%
  • Stage 4 (heart disease, with or without kidney disease) – 9.2%

In other words, half of US adults have moderate CKM syndrome risks (Stage 2), and nearly a sixth of adult Americans already have advanced CKM syndrome (Stages 3 & 4). Yikes.

These rates stayed relatively stable throughout the study period, while certain groups were far more likely to have advanced stage CKM syndrome including those older than 65 (55.3% vs. 10.7% in 45-64yrs), men (16.9% vs. 12.4% in Women), and Black people (18.9% vs. 13.8% in Whites).

The Takeaway

Many Cardiac Wire readers shouldn’t be surprised by these numbers, noting the mounting evidence that diabetes, obesity, and hypertension rates are skyrocketing. However, the fact that 90% of US adults have high CKM syndrome risks is still shocking, and underscores the urgent need to improve CKM prevention and care.

Aspirin’s Lp(a) Primary Prevention Potential

Posted on by Jake Fishman

An observational study out of Emory suggests that aspirin could be the preventative Lp(a) treatment we’ve been looking for, finding that people with high Lp(a) levels who regularly take aspirin might significantly reduce their ASCVD mortality risks. 

The researchers analyzed 26-year outcomes from 2,990 people without clinical ASCVD (representative of 73M US adults), including 7% who regularly took aspirin, finding that…

  • Among participants with high Lp(a) levels, daily aspirin-takers had far lower ASCVD mortality rates per 1,000 person-years than those who didn’t regularly take aspirin (1.2 vs. 3.9).
  • Multivariable modeling revealed that regular aspirin was associated with a 52% lower risk of ASCVD mortality among high Lp(a) participants, but not in aspirin-takers who didn’t have high Lp(a).

The fact that aspirin-takers who had high Lp(a) levels had 52% lower mortality risks compared to the aspirin-takers with normal Lp(a) levels got people talking on CardioTwitter, leading to a number of theories (e.g. aspirin’s inflammation benefits), and criticisms (e.g. the study’s reliance on observational and survey data), while most online commenters called for an RCT to know for sure.

Until we get an RCT, any supporters or doubters of this research might be interested to see a pair of previous studies that found high-Lp(a) individuals who regularly took aspirin had a 46% lower risk of coronary heart disease events and 45-55% lower MACE risks.

The Takeaway

Around 20% of people have high Lp(a) levels, but there’s currently no FDA-approved Lp(a) treatment, which creates little reason for Lp(a) testing. A lot more research is needed, but if aspirin truly does prove to slash ASCVD mortality, it could address Lp(a)’s treatment and testing problems, and have a major public health impact in the process.

Statins’ Diabetes Risks and Benefits

Posted on by Jake Fishman

A new Lancet study brought statins’ diabetes risks back into the headlines, showing that statins do indeed drive significant increases in new diabetes diagnoses, while arguing that statins’ cardiovascular benefits still far outweigh their diabetes risks.

Researchers from the Cholesterol Treatment Trialists’ Collaboration analyzed 19 RCTs comparing statins versus a placebo (n= 124k, 21% w/ diabetes, 4.3yr median follow up) and four RCTs comparing low and high-intensity statin therapies (n= 31k, 17% w/ diabetes, 4.9yr median follow up), finding that…

  • Low- or moderate-intensity statin therapy drove a 10% relative increase in new-onset diabetes versus placebo (2,420 of 39,179 vs. 2,214 of 39,266 participants).
  • High-intensity statin therapy drove a 36% relative increase in new-onset diabetes versus placebo (1,221 of 9,935 vs. 905 of 9,859 participants).

Those are concerning numbers at first glance, however further analysis revealed that future diabetes diagnoses were largely influenced by baseline HbA1c levels and follow-up testing.

  • Among participants without baseline diabetes, mean glucose increased by just 0.04 mmol/L in statin-takers, while HbA1c increased by 0.06% in patients receiving low/moderate statins and by 0.08% in patients receiving high-intensity statins.
  • Among patients with baseline glycaemia, 62% of new new-onset diabetes cases involved participants who were already in the top quartile of glycaemic levels.
  • The rate of new-onset diabetes was mainly dependent on how many participants actually received follow-up HbA1c tests (so more testing drove more positives…), and the analysis’ high-intensity statin trials were much more likely to include follow-up HbA1c tests (explaining higher diabetes rates w/ high-intensity statins).

These results revived statin diabetes debates on MedTwitter, with one extremely prominent physician highlighting statins’ diabetes risks, and others suggesting that this study adds evidence that statins’ diabetes risks aren’t “clinically relevant” since statins are proven to reduce mortality.

The Takeaway

Although the link between statins and diabetes is widely known, this analysis shows that the majority of new diabetes diagnoses are happening in statin-takers who already had “baseline glycaemic markers that are close to the diagnostic threshold for diabetes.” 

That’s worth keeping in mind for the many borderline diabetic patients who are taking statins (or could be soon), but it’s also worth keeping in mind the authors’ primary message that statins’ absolute benefits “greatly outweigh any excess risks of diabetes.”

Questioning Intermittent Fasting’s Cardiovascular Impact

Posted on by Jake Fishman

A new AHA study shocked the world this week, suggesting that intermittent fasting might significantly increase people’s risk of cardiovascular death, sparking a wave of media coverage, and a frenzy of criticisms from the cardiologist and scientific communities.

  • Time-restricted eating, which is a type of intermittent fasting, involves limiting eating to a specific number of hours per day (e.g. 4 or 8 hours) and fasting for the rest of the day.
  • Intermittent fasting has risen in popularity due to a range of reported benefits to weight, cardiometabolic health, energy, and cognition.

This study set out to evaluate whether these perceived short-term benefits might lead to some serious long-term problems. 

A team of researchers from Wuhan University in China analyzed data from around 20k US adults from the 2003-2018 NHANES database (avg. age 49yrs), who had completed two 24-hour dietary recall questionnaires within the first year of enrollment.  

The poor folks who ate all their meals within shorter time frames on the days before those two particular surveys had far worse outcomes over the 8-year median follow-up period.

  • People who ate within an eight hour window had a 91% higher risk of death due to cardiovascular disease.
  • Participants with CVD who ate all their meals within an 8 to 10 hour window had a 66% higher risk of death from heart disease or stroke.

The media quickly jumped all over this story, with a long list of mainstream news outlets detailing how this “healthy” practice might actually be killing people, and even a few cardiology pubs sharing the same conclusion.

However, it didn’t take long for criticisms to start emerging about the study and its media coverage, noting that…

  • These results conflict with far more reliable RCTs that showed intermittent fasting reduces LDL-C, blood pressure, and weight.
  • The study was observational, relied on dietary responses (often unreliable), and didn’t capture the respondents’ baseline cardiometabolic status.
  • The NHANES survey didn’t ask if these people were following time-restricted diets, they just asked what times they ate during two days. 
  • If you’re not participating in intermittent fasting, not wanting to eat for 16 hours could be a disease symptom or a sign of an unhealthy lifestyle.

The Takeaway

Although we still don’t know whether participating in intermittent fasting diets actually almost doubles cardiovascular mortality risks, a big portion of the population now thinks it does.

Microplastics, Nanoplastics, and Major Cardiac Events

Posted on by Jake Fishman

A landmark NEJM study revealed that many patients with carotid artery disease might have microplastics and nanoplastics (MNPs) embedded in their carotid plaque, and those patients  have a massive 4.5-fold greater risk of heart attack, stroke, or death within three years.

The researchers examined carotid plaque specimens from 257 patients with asymptomatic carotid artery disease, analyzing their plaque for the presence of 11 MNPs, and tracking the patients’ cardiovascular outcomes over 34 months.

  • An alarming 58.4% of patients had polyethylene in their plaque and 12.1% had polyvinyl chloride in their plaque, while no patients had detectable levels of the nine other kinds of plastics. 
  • Even more alarming, 20% of patients with MNPs experienced the primary endpoint (myocardial infarction, stroke, or all-cause death), versus 7.5% in patients without MNPs in their plaque. 
  • After adjusting for variables (e.g. age, BMI, comorbidities, prior events), the presence of MNPs in plaque came with a 4.5-times higher risk of experiencing one of the primary events. Yikes.

The scientists also discovered visual evidence of MNPs’ damage to plaque, as electron microscopy showed “visible, jagged-edged foreign particles” in the MNP-containing plaques and those plaques appeared “more vulnerable, more inflamed.”

None of this sounds good, and clinicians and scientists across social media were extremely alarmed by these findings. 

However, there isn’t enough evidence to confirm that microplastics in plaque directly cause cardiovascular events, for example, the factors that helped introduce the MNPs into these patients (e.g. air pollution) could have had significant overall impacts on their health.

The Takeaway

It’s been quite a while since a study inspired such online uproar, and although we don’t know for sure that microplastics in plaque cause cardiovascular events, we have solid evidence that these patients are much more likely to experience them. We also know that their plaque appears more vulnerable. 

Let’s hope future studies lead to a better understanding of how microplastics are making it into our bodies and the harm they are causing — and they inspire action that leads to fewer and cleaner plastics.

Lipoprotein(a)’s High (and Uneven) Cardiovascular Risks

Posted on by Jake Fishman

Harvard researchers strengthened the link between high Lipoprotein(a) levels and greater risks of future cardiovascular events, including among patients who haven’t been diagnosed with ASCVD.

The researchers analyzed 12-year outcomes from 16,419 people in the Mass General Brigham Lp(a) Registry who had their Lp(a) measured between 2000 to 2019, including 62% with a history of ASCVD (prior MI, revascularization, ischemic stroke).

Patients with ASCVD histories generally had higher Lp(a) levels than those without ASCVD (37.8 vs 31.1 nmol/L), but Lp(a)’s future MACE risks increased at a far steeper rate among the patients without ASCVD. 

Compared to patients in the 1st to 50th percentile of Lp(a) levels, patients in the…

  • 51st to 70th Lp(a) percentiles had a 14% greater MACE risk if they also had ASCVD, and a 9% greater MACE risk if they didn’t have ASCVD.
  • 71st to 90th Lp(a) percentiles had a 21% greater MACE risk if they also had ASCVD, and a 17% greater MACE risk if they didn’t have ASCVD.
  • 91st to 100th Lp(a) percentiles had a 26% greater MACE risk if they also had ASCVD, and a 93% greater MACE risk if they didn’t have ASCVD.

Annual MACE rates were still highest among the patients with ASCVD compared to those without ASCVD across the four Lp(a) percentile levels (annual MACE rates: 4.1%, 4.9%, 5.3%, 5.3% vs. 1.1%, 1.2%, 1.3%, and 2.2%).

  • However, the ASCVD patients’ saw their risk plateau beyond the 70th percentile, while the non-ASCVD patients’ risk significantly increased at the 90th Lp(a) percentile.

Those differences in Lp(a) risk thresholds could have a significant impact on patient screening decisions and patient selection for future Lp(a) trials, especially considering that many patients with high Lp(a) levels wouldn’t be included in the current Lp(a) Phase 3 trials.

The Takeaway

Using real world data, this study further confirms conclusions from previous Lp(a) studies, while revealing that Lp(a)-related MACE risk thresholds can be quite different among primary and secondary prevention patients. That could have a big influence on future trials, which could in turn have a big influence on future Lp(a) testing and treatment guidelines.

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