Clinical guidelines for 2026 were recently published in Circulation by the American College of Cardiology and the American Heart Association for the management of dyslipidemia, including over 50 new or revised recommendations from the previous (2018) edition. Among the new recommendations are several that have long been advocated for, including several regarding Lp(a), apoB, imaging for subclinical atherosclerosis, etc., that are worth reviewing here. Additionally, the role of environmental toxins in dyslipidemia and cardiovascular disease in general was not included in these recent guidelines, but the clinical implications are reviewed here as well.
ApoB, for example, was not included in the 2018 guidelines, but here it is considered reasonable to guide the intensity of therapy among people on lipid-lowering therapy (LLT), especially those with additional risk factors, and to help enhance ASCVD (Atherosclerotic Cardiovascular Disease) risk assessment and the need for initiating therapy among those not on LLT. It is now understood that although LDL-C is the traditional marker of lipid risk, apoB directly measures the number of atherogenic particles (it can be found on LDL particles, VLDL particles, and Lp(a)), better capturing true atherogenic risk. Indeed, “an apoB particle is the basic unit of injury to the arterial wall.” The new guidelines also highlight that apoB is a better determinant of risk than LDL-C, noting its superior prediction of ASCVD risk when LDL-C and apoB are discordant. For example, even when LDL-C is at target, an elevated apoB indicates “persistent atherogenic particle burden and potential need for therapy intensification,” which is more likely to occur in the presence of cardiometabolic disease, diabetes, etc. It’s also worth noting that the price of apoB testing is low, the measurement is standardized, and a fasting sample is not required.
Lp(a), an LDL-like particle containing apoprotein(a) bound to an apoB-100 component, is also mentioned among the new recommendations. Because Lp(a) levels are determined by the LPA gene (and thus remain consistent over the lifespan), the new guidelines recommend testing at least once in all adults to determine ASCVD risk, with additional recommendations for people with familial hyperlipidemia as well as appropriate testing methods. Lp(a) appears to have a causal relationship with aortic valve disease and other ASCVD outcomes (as well as all-cause mortality), with risk increasing in a continuous manner and independently of LDL-C. Compared to reference levels of <75 nmol/L (<30 mg/dL), an increase to 75–124 nmol/L is associated with a 20% increase in ASCVD risk, 125 nmol/L with a 40% increase, and a 400% increase at levels of 430 nmol/L and above. While fasting is also not required for Lp(a), standardization is still needed, with a preference for calibration in molar units (i.e., nmol/L) and the use of methods that are apo(a) isoform-insensitive.
The guidelines also included recommendations for imaging, i.e., coronary artery calcium (CAC), among adults with subclinical atherosclerosis. Specifically, CAC can help to assess risk among individuals at borderline to intermediate 10-year ASCVD risk, as CAC scores are linearly associated with MACE (Major Adverse Cardiovascular Events). CAC scores range from 0 (no coronary plaque burden) to > 1000 AU, indicative of extensive coronary plaque and a nearly 2-fold risk of cardiovascular disease mortality compared to levels of 400 to 999 AU. It should also be pointed out that the guidelines recommend assessing risk using the PREVENT-ASCVD equations for adults aged 30-79 without ASCVD or subclinical atherosclerosis, and an LDL-C between 70 and 189 mg/dL. Low risk is defined as <3% over 10 years, borderline as 3 to <5%, intermediate as 5 to < 10%, and high as 10+. The guidelines suggest that LLT may be avoided for adults with borderline to intermediate risk (and no additional risk factors) and a CAC of 0, with repeat testing indicated at 3 to 7 years.
A controversial recommendation was also made in this latest edition, advising against the use of supplements to lower LDL-C or triglycerides. This recommendation was made largely based on the results of one study published in 2023 in the Journal of the American College of Cardiology, which has been heavily criticized. This single-blind trial, referred to as SPORT (Supplements, Placebo, or Rosuvastatin Study), contained 8 different groups: placebo, rosuvastatin, and either fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice, and lasted a total of 28 days. Funded by AstraZeneca, 190 participants (ages 40 to 75 with an LDL-C of 70 to 189 mg/dL but no history of ASCVD) completed this trial, evenly divided between groups (22 to 25 in each group completed the trial), with the primary endpoint being the percent change in LDL-C. None of the supplements (each a different brand) significantly lowered LDL-C at 28 days, but rosuvastatin led to a significant 35.2% reduction compared to placebo.
As published in a commentary to this study (also in the Journal of the American College of Cardiology), however, there are several concerns about the study. In addition to being only a single-blind study (with no explanation why it was not double-blinded), the small group size may not have been large enough to rule out a benefit, and the 28-day study may not have been long enough to show a benefit for supplements that require longer use. As the authors point out, red yeast rice has been shown to lower LDL-C by 15 to 25% within 6 to 8 weeks, and the short duration of this study may not have been sufficient to observe this effect. There is also variability in quality between manufacturers, a valid point emphasized by the authors of the 2023 study, but no testing was done on the included products to verify their content, or explanation as to why each brand was chosen.
The study also did not address the potential of supplements used in combination, the tolerability of lipid-lowering supplements, or the complementary effects they may have on cardiovascular risk factors other than LDL-C. For example, the Journal of the American College of Cardiology also published a review of the use of nutraceuticals among statin-intolerant patients. Given that the long-term adherence to statins is approximately 50%, nutraceuticals that could be maintained long-term and have other non-lipid-lowering properties may be an important alternative. For example, this review cites anti-inflammatory, antithrombotic, and antioxidant effects, and combinations may address multiple targets. Fish oil combined with red yeast rice, for instance, was shown in a double-blind and randomized controlled 8-week trial to have favorable effects on lipids, including a 17.3% reduction in LDL-C, a 22.3% reduction in apoB, a 14.9% decrease in hsCRP, as well as a significant improvement of pulse volume change by 5.0%, at fairly low doses of both ingredients. Thus, not only was there a significant drop in lipid levels, but this was coupled with an improvement in endothelial function and a positive impact on the inflammatory process. In a meta-analysis of 15 high-quality randomized and controlled trials published in Frontiers in Pharmacology, red yeast rice had a synergistic effect when combined with nutraceuticals, more effectively lowering total and LDL cholesterol, as well as triglycerides. When used alone, red yeast rice significantly reduced apoB (mean difference of -27.98), which, as mentioned above, is a more accurate predictor of ASCVD risk than LDL-C.
The new guidelines also provided more specific recommendations for dietary management of healthy lipids. In addition to promoting fruits and vegetables, nuts and seeds, fiber-rich foods (legumes and whole grains), and monounsaturated and polyunsaturated fats, and avoiding saturated fats, they also mention specific dietary components/approaches. For example, despite many studies demonstrating the cardioprotective effects of a Mediterranean diet, there may be advantages to a completely plant-based diet. They cite a randomized 16 week crossover trial, published in the Journal of the American Nutrition Association, comparing the Mediterranean diet to a vegan diet; the vegan diet resulted in more weight loss (6 kg vs. 0), significant improvements in insulin sensitivity (Homeostasis Model Assessment, HOMA-IR, and oral glucose insulin sensitivity, OGIS) with no change while on the Mediterranean diet, and a significant reduction in LDL-C (15.3 mg/dL) only on the vegan diet. Both diets improved blood pressure, with more of an effect while on the Mediterranean diet. They also refer to an older study published in JAMA describing the potent lipid-lowering effects of the Portfolio diet, which emphasizes plant sterols, soy protein, viscous fibers, and nuts. Mean LDL-C was lowered by 26 mg/dL in this 6-month trial, with similar attrition rates between the Portfolio diets and the control diet. Other suggested interventions in the new guidelines include incorporating nuts, fiber (such as oatmeal), and replacing meat with plant-based protein.
Recommendations for physical activity, specifically, aiming for at least 150 minutes per week of moderate-to-vigorous intensity aerobic exercise as well as 2 days per week of upper and lower body resistance exercise, were also included in the new guidelines. One of the supporting citations was a systematic review and meta-analysis of 148 randomized and controlled trials published in Sports Medicine in 2025. Exercise training modestly but significantly improved all five lipid measures included in the analysis (by 3.5% to 11.7%), with the largest benefits observed for combined training (e.g., aerobic and resistance exercise).
Unfortunately, this recent update for the management of dyslipidemia made no mention of the role of environmental toxins in cardiovascular disease development or progression, and it is worth reviewing some of the key research published in the last few years.
A 2026 paper, for example, published in the American Journal of Epidemiology described a longitudinal quasi-experimental study that compared data from nearly 9,000 adults, some of whom had consistently high exposure to air pollution (marked by PM2.5 levels ≥25 μg/m3), and some of whom had a decrease from high to low pollution during the 18-year period (either by relocation or by pollution reduction). Although not a clinical trial, which would be quite difficult to conduct, this study suggested that improvements in air quality were associated with a 25% reduction in the risk for dyslipidemia. This included nearly a 40% reduction in the risk for elevated total cholesterol, a 31% reduction in the risk of elevated LDL-C, and a 41% reduction in the risk for low HDL-C. This was consistent with another study published in 2026 in BMC Public Health, which found that PM2.5 constituents, particularly nitrate, were associated with dyslipidemia, particularly among older adults.
Per- and polyfluoroalkyl substances (PFAS) have emerged as a potentially important contributor to dyslipidemia and cardiovascular disease. A case-control study published in Environmental Health was conducted in the Health Professionals Follow-Up Study (HPFS) and Nurses' Health Study (NHS) and found that several PFAS had positive dose-responses for coronary heart disease (CHD), specifically, total perfluorooctane sulfonic acid (PFOS), branched PFOS (brPFOS), and linear PFOS (nPFOS) were each associated with between a 3 to 4-fold risk for developing CHD. A 2025 systematic review and meta-analysis published in Environmental Science & Technology included 74 epidemiological studies that found perfluorooctanoic acid (PFOA) and PFOS exposure were associated with increased total cholesterol and LDL-C in adults. In 2025, Frontiers in Cardiovascular Medicine published data from the 2005 to 2012 National Health and Nutrition Examination Survey (NHANES). Although this was a retrospective study, several PFAS were positively correlated with cardiovascular disease, including perfluorodecanoic acid (PFDE), 2-(N-methyl perfluorooctane sulfonate (MPAH), and perfluoroundecanoic acid (PFUA), with interactions between gender and race. In addition to dyslipidemia and cardiovascular disease, PFAS have been linked to increased inflammation and adverse impacts on glucose metabolism; given the diversity of PFAS, it’s likely they promote atherosclerosis through multiple interconnected mechanisms that effectively promote vascular aging. It’s important to emphasize that a recent analysis of NHANES data found that 96% of teenagers, some of whom were born after legacy PFAS production declined, had detectable levels of these compounds in their blood, indicating ubiquitous exposure to these “forever chemicals.” And although industry has reduced the use of legacy compounds, a 2023 review found that 7 million (and growing) PFAS compounds are found in the database PubChem, with over 1400 individual PFAS (as of 2022) used industrially, in fast-food containers, anti-staining materials, fire-suppressing foams, etc. It’s difficult to assess the cardiovascular impact of compounds we don't measure, as only a few legacy PFAS are included in national surveillance programs.
A number of heavy metals, including lead, cadmium, mercury, and barium, have been linked individually and combined to an increase in the risk for dyslipidemia. For example, an analysis of NHANES data found that these four heavy metals (individually and in combination) increase the risk of high remnant cholesterol, also known as triglyceride-rich lipoprotein cholesterol, which penetrates the sub-endothelial spaces of arterial walls and plays a causal role in ASCVD.
Metals appear to play an oversized role in contributing to cardiovascular disease which is not generally appreciated (as evidenced by the lack of a mention in the recent guidelines). For example, the journal Lancet Public Health published an analysis of NHANES data that included over 14,000 adults, examining blood lead levels and mortality over a mean follow-up of over 19 years. An increase in blood lead from the 10th to the 90th percentile (at that time, this was 1.0 μg/dL to 6.7 μg/dL) was associated with a 37% increase in all-cause mortality, a 70% increase in CVD mortality, and a 108% increase in ischemic heart disease mortality. Even more striking, the population attributable fraction of lead in blood for all-cause mortality was 18.0%, 28.7% for CVD mortality, and 37.4% for ischemic heart disease mortality. In other words, if lead exposure could have been completely eliminated, roughly one-third of the CVD and ischemic heart disease deaths would have been prevented. Perhaps even more surprising, a subsequent analysis of NHANES data estimating bone lead levels suggests that the Lancet’s findings were an underestimate. This publication was aptly titled “Do we underestimate risk of cardiovascular mortality due to lead exposure?” and included data from over 11,000 participants and a mean follow-up of nearly 27 years. While the all-cause mortality associated with bone lead was similar to that for blood lead, cardiovascular mortality was much higher; for example, the 90th to 10th percentile comparison for tibia bone lead levels was associated with a 232% increase in CVD mortality. When considering tibia bone lead levels, the authors determined that if everyone in the U.S. declined to levels in the 10th percentile, the population attributable fraction for cardiovascular mortality was 45.8%, an astonishing figure.
The latest guidelines for the management of dyslipidemia include many changes that are likely to improve cardiovascular health, such as the long-awaited promotion of apoB testing and its superior ability to assess ASCVD risk, the utility of at least one-time testing for Lp(a), and the use of imaging (e.g., coronary artery calcium) for subclinical atherosclerosis to guide therapy decisions. Lacking from the guidelines are any mention of environmental toxins and the outsized role they play in promoting cardiovascular disease, as well as a recognition of the value of nutraceuticals proven individually and in combination to aid in the management of cardiovascular health.
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