In this review, we would like to mention articles in recent months and trials presented at ACC 23 that have implications for our clinical practice. They are categorized as per the subsets of cardiology.
Valvular Heart Disease
Three-Year Outcomes After Transcatheter or Surgical Aortic Valve Replacement in Low-Risk Patients with Aortic Stenosis.
Forrest JK, Deeb GM, Yakubov SJ, Gada H, Mumtaz MA, Ramlawi B, Bajwa T, Teirstein PS, DeFrain M, Muppala M, Rutkin BJ, Chawla A, Jenson B, Chetcuti SJ, Stoler RC, Poulin MF, Khabbaz K, Levack M, Goel K, Tchétché D, Lam KY, Tonino PAL, Ito S, Oh JK, Huang J, Popma JJ, Kleiman N, Reardon MJ; Low-Risk Trial Investigators. J Am Coll Cardiol. 2023 Feb 24:S0735-1097(23)00411-4. doi: 10.1016/j.jacc.2023.02.017. Epub ahead of print. PMID: 36882136.
Background:
Randomized data comparing outcomes of transcatheter aortic valve replacement (TAVR) to surgery in low surgical risk patients at time points beyond 2 years is limited. This presents an unknown for physicians striving to educate patients as part of a shared decision-making process.
Objective:
We evaluated 3-year clinical and echocardiographic outcomes from the Evolut Low-Risk trial.
Methods:
Low-risk patients were randomized to TAVR with a self-expanding, supra-annular valve or surgery. The primary endpoint of all-cause mortality or disabling stroke and several secondary endpoints were assessed at 3 years.
Results:
There were 1414 attempted implants (730 TAVR; 684 surgery). Patients had a mean age of 74 years and 35% were women. At 3 years, the primary endpoint occurred in 7.4% of TAVR patients and 10.4% of surgery patients (HR, 0.70; 95% CI, 0.49–1.00; P = .051). The difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; –2.9% at year 3. The incidence of mild paravalvular regurgitation (20.3% TAVR vs 2.5% surgery) and pacemaker placement (23.2% TAVR vs 9.1% surgery; P < .001) were lower in the surgery group. Rates of moderate or greater paravalvular regurgitation for both groups were <1% and not significantly different. Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1mmHg TAVR vs 12.1 mmHg surgery; P < .001) at 3 years.
Conclusions:
Within the Evolut Low-Risk study, TAVR at 3 years showed durable benefits compared to surgery concerning all-cause mortality or disabling stroke.
Comments:
Transcatheter valve implantation is a cutting-edge method of treating valvular heart disease, especially aortic stenosis. With increasing evidence, advancements in valve technology, and resolving periprocedural problems, the TAVR is determined to be superior to surgical replacement in moderate- and high-risk patients. The subset of patients with low risk has insufficient data about the efficacy of TAVR. This trial demonstrates the long-lasting advantages of TAVR compared to SAVR with effective hemodynamics and fewer periprocedural problems. Regarding durability, late problems, and the need for repeat surgery, this subset of patients needs to be followed up with over an extended period.
Midterm Outcomes of Underweight Patients Undergoing Transcatheter Aortic Valve Implantation Insight From the LAPLACE-TAVR Registry
Tezuka T, Higuchi R, Hagiya K, et al. JACC: Asia. 2023 Feb;3(1):78-89.
Background:
Obesity is a major risk factor for cardiovascular disease; however, a paradoxical effect of obesity has been reported in patients with heart failure or myocardial infarction. Although several studies have suggested the same obesity paradox in patients undergoing transcatheter aortic valve replacement (TAVR), they included a limited number of underweight patients.
Objectives
: This study aimed to clarify the effect of being underweight on TAVR outcomes.
Methods:
We retrospectively analyzed 1,693 consecutive patients undergoing TAVR between 2010 and 2020. The patients were categorized according to body mass index: underweight (25 kg/m2; n ¼ 396). We compared midterm outcomes after TAVR among the 3 groups; all clinical events were in accordance with the Valve Academic Research Consortium-2 criteria.
Results:
Underweight patients were more likely to be women and have severe heart failure symptoms, peripheral artery disease, anemia, hypoalbuminemia, and pulmonary dysfunction. They also had lower ejection fractions, smaller aortic valve areas, and higher surgical risk scores. Device failure, life-threatening bleeding, major vascular complications, and 30-day mortality occurred more frequently in underweight patients. The midterm survival rate of the underweight group was inferior to those of the other 2 groups (P < .0001; the average follow-up, 717 days). In the multivariate analysis, being underweight was associated with noncardiovascular mortality (HR: 1.78; 95% CI: 1.16-2.75) but not cardiovascular mortality (HR: 1.28; 95% CI: 0.58-1.88) after TAVR.
Conclusions
: Underweight patients had a worse midterm prognosis, demonstrating the obesity paradox in this TAVR population.
Comments:
This study highlights the obesity paradox in the TAVR group. However, like other categories, underweight patients do not have excess cardiovascular mortality. The poor lung capacity kept people at risk of pneumonia, which contributed more to the increased noncardiovascular mortality. Aside from early intervention, strategies for treating underweight individuals’ diet and physical capability should be considered. The focus of the future studies should be on more in-depth analyses such as lean body mass, muscular mass, and adipose tissue distribution.
Pulmonary Hypertension
Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension
Hoeper MM, Badesch DB, Ghofrani HA, Gibbs JSR, Gomberg-Maitland M, McLaughlin VV, Preston IR, Souza R, Waxman AB, Grünig E, Kopeć G, Meyer G, Olsson KM, Rosenkranz S, Xu Y, Miller B, Fowler M, Butler J, Koglin J, de Oliveira Pena J, Humbert M; STELLAR Trial Investigators. N Engl J Med. 2023 Apr 20;388(16):1478-1490. doi: 10.1056/NEJMoa2213558. Epub 2023 Mar 6. PMID: 36877098.
Background:
Pulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, disease-associated morbidity, and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.
Methods:
We conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary endpoint was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary endpoints, tested hierarchically in the following order, were a multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro–B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension–Symptoms and Impact (PAH-SYMPACT) Physical Impacts, cardiopulmonary symptoms, and cognitive-emotional impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit.
Results:
A total of 163 patients were assigned to receive a sotatercept and 160 to receive a placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, −0.3 to 3.5) in the placebo group. The Hodges-Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P < 0.001). The first 8 secondary endpoints were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive-Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.
Conclusions:
In patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo.
Comments:
According to the STELLAR trial, Sotatercept, an activin signaling inhibitor, improves 6MWD in persons with symptomatic PAH who are receiving background medication better than a placebo. The medication arsenal for treating PAH is expanding, and the patient’s physical state is being improved with efficiency of these drugs.
Lipidology
Clear trial - bempedoic acid and cardiovascular outcomes in statin-intolerant patients
Nissen SE, Lincoff AM, Brennan D, Ray KK, Mason D, Kastelein JJP, Thompson PD, Libby P, Cho L, Plutzky J, Bays HE, Moriarty PM, Menon V, Grobbee DE, Louie MJ, Chen C-F, Li N, Bloedon L, Robinson P, Horner M, Sasiela WJ, McCluskey J, Davey D, Fajardo-Campos P, Petrovic P, Fedacko J, Zmuda W, Lukyanov Y, Nicholls SJ; CLEAR Outcomes Investigators. N Engl J Med. 2023 Apr 13;388(15):1353-1364. doi: 10.1056/NEJMoa2215024. Epub 2023 Mar 4.
Background
: Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels, and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.
Methods:
We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (“statin-intolerant” patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or a placebo. The primary endpoint was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.
Results:
A total of 13,970 patients underwent randomization, 6992 were assigned to the bempedoic acid group, and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = .004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = .006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = .002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.
Conclusions:
Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.)
Comments: Bempedoic acid is a potent alternative medication that effectively lowers the LDL C and has CRP by about 20% in statin-intolerant patients. In statin intolerant patients, PCSK9 inhibitors are drug of choice; however, majority of patients are reluctant to take injections and they are costly. Bempedoic acid fills the void because it is an oral medication, and is effective in lowering LDL cholesterol. Majority of the trial participants are female (40%), which should be kept in mind while dealing these patients.
Ischemic Heart Disease
Effect Of Myocardial Viability, Percutaneous Coronary Intervention, And Functional Recovery On Clinical Outcomes In The REVIVED-BCIS2 Randomized Trial. Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction
Perera D, Clayton T, O’Kane PD, Greenwood JP, Weerackody R, Ryan M, Morgan HP, Dodd M, Evans R, Canter R, Arnold S, Dixon LJ, et al., for the REVIVED-BCIS2 Investigators. N Engl J Med. 2022;387:1351-1360. doi: 10.1056/NEJMoa2206606
Background:
Whether revascularization by the percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (ie, individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown.
Methods:
We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores.
Results:
A total of 700 patients underwent randomization—347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P = .96). The left ventricular ejection fraction was similar in the 2 groups at 6 months (mean difference, −1.6 percentage points; 95% CI, −3.7-0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, −1.7-3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference diminished at 24 months.
Conclusions:
Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure.
Comments: The benefit of revascularization in hibernating myocardium is a topic of debate. Although PCI did not improve LV dysfunction in this trial when compared to OMT, it did lessen the occurrence of VT/VF in patients with ICDs (25% of the patients had an ICD). Similarly, the occurrence of spontaneous MI reduced in the PCI arm. In approximately 2/3 patients, there was no angina and the recruitment was based on viable myocardium, which did not have any effect on mortality in the STICH trial. Long follow up of this subset of patients are required before concluding that PCI has no mortality benefit.
Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome: The H-REPLACE Randomized Equivalence and Noninferiority Trial
Zhou S, Xiao Y, Zhou C, Zheng Z, Jiang W, Shen Q, Zhu C, Pan H, Liu C, Zeng G, Ge L, Zhang Y, Ouyang Z, Fu G, Pan G, Chen F, Huang L, Liu Q; H-REPLACE Investigators. JAMA Netw Open. 2023 Feb 1;6(2):e2255709. doi: 10.1001/jamanetworkopen.2022.55709. PMID: 36763358; PMCID: PMC9918885.
Importance:
Parenteral enoxaparin is a preferred anticoagulant used in the acute phase for patients with acute coronary syndrome (ACS). The safety and efficacy of short-term low-dose rivaroxaban in this clinical setting remain unknown.
Objective:
To compare the safety and efficacy of rivaroxaban vs enoxaparin in the acute phase of ACS.
Design, setting, and participants:
This multicenter, prospective, open-label, activecontrolled, equivalence and noninferiority trial was conducted from January 2017 through May 2021 with a 6-month follow-up at 21 hospitals in China. Participants included patients with ACS missing the primary reperfusion window or before selective revascularization. Data were analyzed from November 2021 to November 2022.
Interventions:
Participants were randomized 1:1:1 to oral rivaroxaban 2.5 mg or 5 mg or 1 mg/kg subcutaneous enoxaparin twice daily in addition to dual antiplatelet therapy (DAPT; aspirin 100 mg and clopidogrel 75 mg once daily) for a mean of 3.7 days.
Main outcomes and measures:
The primary safety end point was bleeding events, as defined by the International Society on Thrombosis and Haemostasis, and the primary efficacy end point was major adverse cardiovascular events (MACEs), including cardiac death, myocardial infarction, rerevascularization, or stroke during the 6-month follow-up.
Results:
Of 2055 enrolled patients, 2046 (99.6%) completed the trial (mean [SD] age 65.8 [8.2] years, 1443 [70.5%] male) and were randomized to enoxaparin (680 patients), rivaroxaban 2.5 mg (683 patients), or rivaroxaban 5 mg (683 patients). Bleeding rates were 46 patients (6.8%) in the enoxaparin group, 32 patients (4.7%) in the rivaroxaban 2.5 mg group, and 36 patients (5.3%) in the rivaroxaban 5 mg group (rivaroxaban 2.5 mg vs enoxaparin: noninferiority hazard ratio [HR], 0.68; 95% CI, 0.43 to 1.07; P = .005; rivaroxaban 5 mg vs enoxaparin: noninferiority HR, 0.88; 95% CI, 0.70 to 1.09; P = .001). The incidence of MACEs was similar among groups, and noninferiority was reached in the rivaroxaban 5 mg group (HR, 0.60; 95% CI, 0.31 to 1.16, P = .02) but not in the rivaroxaban 2.5 mg group (HR, 0.68; 95% CI, 0.36 to 1.30; P = .05) compared with the enoxaparin group.
Conclusions and Relevance:
In this equivalence and noninferiority trial, oral rivaroxaban 5 mg showed noninferiority to subcutaneous enoxaparin (1 mg/kg) for patients with ACS treated with DAPT during the acute phase. Results of this feasibility study provide useful information for designing future randomized clinical trials with sufficient sample sizes.
Comments: This study emphasizes that the inclusion of oral NOACs in place of enoxaparin along with DAPT in patients with ACS is noninferior in terms of effectiveness and MACE. However, it should be remembered that the trial was conducted on Chinese people before extrapolating these findings to the rest of the world. The trial’s power is insufficient, and bleeding episodes are not adequately documented. To draw a conclusion, additional research must be conducted with a larger sample size in each area.
Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors
Collison D, Copt S, Mizukami T, Collet C, McLaren R, Didagelos M, Aetesam-ur-Rahman M, McCartney P, Ford TJ, Lindsay M, Shaukat A, Rocchiccioli P, Brogan R, Watkins S, McEntegart M, Good R, Robertson K, O’Boyle P, Davie A, Khan A, Hood S, Eteiba H, Berry C, and Oldroyd KG. Circ Cardiovasc Interv. 2023, 4 January;16(4):e012511.
Background:
Twenty percent to 40% of patients are affected by angina after percutaneous coronary intervention (PCI), which is associated with anxiety, depression, impaired physical function, and reduced quality of life. Understanding patient and procedural factors associated with post-PCI angina may inform alternative approaches to treatment.
Methods:
Two hundred thirty patients undergoing PCI completed the Seattle Angina Questionnaire (SAQ-7) and European quality of life–5 dimension–5 level (EQ-5D-5L) questionnaires at baseline and 3 months post-PCI. Patients received blinded intracoronary physiology assessments before and after stenting. A post hoc analysis was performed to compare clinical and procedural characteristics among patients with and without post-PCI angina (defined by follow-up SAQ-angina frequency score <100).
Results:
Eighty-eight of 230 patients (38.3%) reported angina 3 months post-PCI and had a higher incidence of active smoking, atrial fibrillation, and history of previous myocardial infarction or PCI. Compared with patients with no angina at follow-up, they had lower baseline SAQ summary scores (69.48±24.12 versus 50.20±22.59, P < .001) and EQ-5D-5L health index scores (0.84±0.15 versus 0.69±0.22, P < .001). Pre-PCI fractional flow reserve (FFR) was lower among patients who had no post-PCI angina (0.56±0.15 versus 0.62±0.13, P = .003). Percentage change in FFR after PCI had a moderate correlation with angina frequency score at follow-up (r = 0.36, P < .0001). Patients with post-PCI angina had less improvement in FFR (43.1±33.5% versus 67.0±50.7%, P < .001). There were no between-group differences in post-PCI FFR, coronary flow reserve, or corrected index of microcirculatory resistance. Patients with post-PCI angina had lower SAQ-summary scores (64.01±22 versus 95.16±8.72, P ≤ .001) and EQ-5D-5L index scores (0.69±0.26 versus 0.91±0.17, P ≤ .001) at follow-up.
Conclusions:
Larger improvements in FFR following PCI were associated with less angina and better quality of life at follow-up. In patients with stable symptoms, intracoronary physiology assessment can inform expectations of angina relief and quality of life improvement after stenting and thereby help to determine the appropriateness of PCI.
Comments:
Almost one-third of patients experience angina after a PCI. A number of variables, including patient-related ones (comorbidities, active smoking, AF), cardiac ones (epicardial and microvascular blockage, inadequate revascularization, residual ischemia), and noncardiac ones (muscle spasm, gastritis), might cause angina post-PCI. A hint about the degree of angina improvement in this subset of patients will come from the significant difference in FFR pre and post PCI. Because it is a single center study, clinical outcomes are not sufficiently powered. To address this issue, a multicenter, bigger population study is required.
Hypertension
Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension
Freeman MW, Halvorsen Y-D, Marshall W, Pater M, Isaacsohn J, Pearce C, Murphy B, Alp N, Srivastava A, Bhatt DL, and Brown MJ, ; for the BrigHTN Investigators*. N Engl J Med. 2023;388:395-405. doi: 10.1056/NEJMoa2213169
Background:
Aldosterone synthase controls the synthesis of aldosterone and has been a pharmacologic target for the treatment of hypertension for several decades. Selective inhibition of aldosterone synthase is essential but difficult to achieve because cortisol synthesis is catalyzed by another enzyme that shares 93% sequence similarity with aldosterone synthase. In preclinical and phase 1 studies, baxdrostat had 100:1 selectivity for enzyme inhibition, and baxdrostat at several dose levels reduced plasma aldosterone levels but not cortisol levels.
Methods:
In this multicenter, placebo-controlled trial, we randomly assigned patients who had treatment-resistant hypertension, with a blood pressure of 130/80 mm Hg or higher, and who were receiving stable doses of at least 3 antihypertensive agents, including a diuretic, to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The primary endpoint was the change in systolic blood pressure from baseline to week 12 in each baxdrostat group as compared with the placebo group.
Results:
A total of 248 patients completed the trial. Dose-dependent changes in systolic blood pressure of −20.3 mm Hg, −17.5 mm Hg, −12.1 mm Hg, and −9.4 mm Hg were observed in the 2-mg, 1-mg, 0.5-mg, and placebo groups, respectively. The difference in the change in systolic blood pressure between the 2-mg group and the placebo group was −11.0 mm Hg (95% confidence interval [CI], −16.4 to −5.5; P < .001), and the difference in this change between the 1-mg group and the placebo group was −8.1 mm Hg (95% CI, −13.5 to −2.8; P = .003). No deaths occurred during the trial, no serious adverse events were attributed by the investigators to baxdrostat, and there were no instances of adrenocortical insufficiency. Baxdrostat-related increases in the potassium level to 6.0 mmol per liter or greater occurred in 2 patients, but these increases did not recur after withdrawal and reinitiation of the drug.
Conclusions:
Patients with treatment-resistant hypertension who received baxdrostat had dose-related reductions in blood pressure.
Comments:
Another medication is added to the subset with resistant hypertension and its effects on blood pressure were dose-related. Studies using a bigger sample size and longer follow-up are needed since hyperkalaemia is of concern.
Preventive Cardiology
Folate, Vitamin B6, and Vitamin B12 Status in Association With Metabolic Syndrome Incidence
Zhu J, Chen C, Lu L, Shikany JM, D’Alton ME, Kahe K. JAMA Network Open. 2023;6(1):e2250621. doi:10.1001/jamanetworkopen.2022.50621.
Importance:
The associations of B vitamin status with metabolic syndrome (MetS) incidence among the US population remain unclear.
Objective:
To investigate intakes and serum concentrations of folate, vitamin B6, and vitamin B12 in association with MetS risk in a large US cohort.
Design, setting, and participants:
This prospective study included Black and White young adults in the US who were enrolled from 1985 to 1986 and studied until 2015 to 2016. Diet was assessed using a validated diet history at examination years 0, 7, and 20. Serum concentrations of folate, vitamin B6, and vitamin B12 were assayed at examination years 0, 7, and 15 in a subset of 1430 participants. MetS was ascertained by clinic and laboratory measurements and self-reported medication use. Data were analyzed between January and July 2021.
Exposures:
Intakes and serum levels of folate, vitamin B6, and vitamin B12.
Main outcomes and measures:
Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for the associations of energy-adjusted B vitamin intakes or serum B vitamin levels with incident MetS.
Results:
The study included 4414 participants, with 2225 Black individuals (50.4%) and 2331 women (52.8%). The mean (SD) age at baseline was 24.9 (3.6) years. A total of 1240 incident MetS cases occurred during the 30 years (mean [SD], 22.1 [9.5] years) of follow-up. Compared with the lowest quintile of each energy-adjusted B vitamin intake, the HRs for incident MetS in the highest quintile were 0.39 (95% CI, 0.31-0.49) for folate (P for trend < .001), 0.61 (95% CI, 0.46-0.81) for vitamin B6 (P for trend = .002), and 0.74 (95% CI, 0.58-0.95) for vitamin B12 (P for trend = .008) after adjustment for potential confounders. Similarly, significant inverse associations were observed in the subset with serum data on these B vitamins (folate: HR, 0.23; 95% CI, 0.17-0.33; P for trend < .001; vitamin B6: HR, 0.48; 95% CI, 0.34-0.67; P for trend < .001; and vitamin B12: HR, 0.70; 95% CI, 0.51-0.96; P for trend = .01).
Conclusions and relevance:
This prospective cohort study found that intakes and serum concentrations of folate, vitamin B6, and vitamin B12 were inversely associated with incident MetS among Black and White young adults in the US.
Comments:
This 20-year long follow-up study based on vitamin intake in the diet highlights the inverse relationship between healthy eating practices and the development of metabolic syndrome.
