INTRODUCTION
Chronic noncommunicable diseases (NCDs) are the leading cause of death and disability worldwide. In the Americas, they account for approximately 5.5 million deaths annually, about 50% of which occur in people aged 30-69 years. (1)
NCDs are associated with modifiable behavioral risk factors such as unhealthy diets, physical inactivity, smoking, excessive alcohol consumption, inadequate restorative sleep, poor stress management, and low social connectivity, which contribute to the development of obesity, fatty liver, hypertension, dyslipidemia, and insulin resistance. (2)
Lifestyle Medicine (LM) is a discipline that promotes, based on scientific evidence, the prescription of healthy habits aimed at the prevention and management of NCDs. It includes interventions that encourage healthy eating, regular physical activity, stress management, restorative sleep, avoidance of risky substances, and positive social connections. (3)
Among the most effective LM interventions are plant-based diets, characterized by the predominance of plant-based foods and the partial or total exclusion of animal products, with proven benefits in type 2 diabetes, hypertension, dyslipidemia, and obesity. (4)
Several studies have evaluated these effects: the Adventist Health Study 2 reported lower cardiovascular mortality in vegetarians and vegans in comparison with omnivores, (5) while the Atherosclerosis Risk in Communities (ARIC) study showed that higher adherence to an overall plant-based diet index is associated with lower cardiovascular risk. (6) The EPIC-Oxford study found a lower incidence of coronary artery disease in vegetarians compared to omnivores, (7) and the BROAD study demonstrated significant reductions in body mass index (BMI), lipid profile, and glycated hemoglobin in patients with obesity or cardiovascular disease. (8)
Chronic stress, defined as sustained neurohormonal activation in response to adverse situations, is a significant cardiovascular risk factor that promotes low-grade chronic inflammation, endothelial dysfunction, and progression of atherosclerosis. (9)
Regular physical activity not only improves cardiovascular and metabolic health but also promotes mental well-being, cognitive function, sleep quality, and social interaction; it encourages healthy coping mechanisms and enhanced self-perception. Physical exercise has been shown to reduce blood pressure, improve the lipid profile, increase insulin sensitivity, and decrease low-grade systemic inflammation. (10) In addition, prospective studies such as the Harvard Alumni Health Study and the Aerobics Center Longitudinal Study have confirmed that sufficient physical activity is associated with a lower incidence of coronary artery disease, stroke, type 2 diabetes, and all-cause mortality. (11,12)
Insufficient or poor-quality sleep is associated with an increased risk of hypertension, obesity, insulin resistance, and cardiovascular disease. Improving sleep duration and quality has demonstrated beneficial effects on the immune system, hormonal balance, and appetite regulation. (13)
Likewise, positive social connections are protective factors against cardiovascular disease, cognitive impairment, and premature mortality. Social isolation and loneliness have been shown to exert a negative impact comparable to that of traditional risk factors such as hypertension or obesity. (14)
Furthermore, within a framework of spirituality that transcends religiosity and involves a set of moral, emotional, and behavioral values and attitudes toward the world, there is growing evidence of its benefits in terms of cardiovascular risk, mortality, and, in particular, blood pressure control. (15)
New community health programs are needed to promote the adoption of healthy habits. Therefore, the objective of this study was to determine the impact of a lifestyle intervention, referred to as the “21Day Plan” on the anthropometric and biochemical parameters as well as cardiovascular risk in a group of patients who regularly attended a private healthcare facility in Entre Ríos between March 2020 and October 2023.
METHODS
This study was conducted in the province of Entre Ríos, Argentina, over a period of 3 years and 6 months. Patients referred from different medical specialties were invited to participate. After being duly informed about the project, they voluntarily decided to enroll in the 21-Day Plan, which involved a specific cost paid by each participant. The identity and personal information of participants were kept confidential throughout the process.
Adults aged 18 years or older were invited to participate in the research by signing an informed consent form included in the admission document. All activities related to the development and implementation of the study complied with the principles of the Declaration of Helsinki. (16)
A total of 171 people registered, of whom 59 met the inclusion criteria, regardless of nationality, race, sex, religion, age, pre-existing conditions, or treatments. All participants were from Argentina and Uruguay.
Inclusion criteria required participants to have at least one modifiable and measurable risk factor (hypertension, dyslipidemia, type II diabetes, obesity), acceptable functional capacity (FC I and FC II according to the New York Heart Association scale) to carry out the physical activities involved in the plan, and adequate cognitive ability to understand the tasks to be performed.
A subgroup of patients not covered by the cardiovascular risk score used in this study was excluded, based on standardized variables within the score (age between 40 and 79 years, total cholesterol between 155 and 309 mg/dL). Due to the virtual format adopted partly because of the COVID-19 pandemic and partly due to the geographical origin of some participants as well as the impossibility of collecting complete laboratory and clinical data, an additional 110 patients were excluded.
A quasi-experimental, pre- and post-, single-group, analytical and descriptive study was conducted in both face-toface and virtual formats, involving a multidisciplinary team of professionals from Cardiology, Nutrition, Psychology, Chaplaincy, and Physical Education.
Data collection was performed between March 2020 and October 2023, following both face-to-face and virtual interviews with the Lifestyle Medicine team. (17) BMI was calculated as weight in kilograms divided by height in meters squared. Based on BMI, patients were classified into three categories: normal weight (<25 kg/m2), overweight (≥25 and <30 kg/m2) and obesity (≥30 kg/m2), which was further divided into grade 1 (≥30 and < 35 kg/m2), grade 2 (≥35 and <40 kg/m2) and grade 3 (≥ 40 kg/m2).
Fasting blood samples were collected before starting the plan and immediately after its completion, using Abbott Alinity automated analyzers. (18) The following parameters were measured: lipid profile and atherogenic index, complete blood count, blood glucose, insulin, and glycated hemoglobin, renal function (urea and creatinine), vitamin D, vitamin B12, homocysteine, and high-sensitivity C-reactive protein (hs-CRP).
The World Health Organization (WHO) cardiovascular risk chart was used to estimate the overall 10-year cardiovascular risk. (19)
The 21-Day Plan consisted of 21-day prescription of a plant-based diet combined with personalized physical activity, as well as psychological and spiritual support. It aimed to assess whether this intervention could modify the aforementioned parameters in the short term to confirm its benefits and potentially incorporate it as a long-term lifestyle. Participants received a schedule of appointments assigned by time slots and for the same day, and a roadmap designed by the Lifestyle Medicine team (see Annex 1).
The cardiologist took each patient’s case history, including, personal data, personal and family history, previously diagnosed conditions, and current treatment, as well as a physical examination and identification of any symptoms that might contraindicate physical activity. The cardiologist also ordered blood tests and any other preliminary studies necessary according to each patient’s risk.
Physical trainer provided a personalized and progressive exercise program, specifying frequency and intensity, according to each patient’s characteristics and ability to perform the prescribed activities, and based on the cardiologist’s prior assessment. Nutrition Department provided a plant-based diet plan with various food options and daily guidelines (see Annex 2), as well as a weekly virtual workshop.
The psychologist and the team chaplain provided psychological and spiritual support during the intervention, with face-to-face or virtual follow-up (via video call or WhatsApp group). In addition, virtual workshops were held via Zoom, each addressing specific topics presented by the corresponding professional and offering space for questions and experience sharing.
Data was entered and analyzed using JASP statistical package, version 0.95.0 for Windows. For univariate analysis, frequencies, means, and standard deviations were calculated according to the type of variable. For bivariate analysis, paired t-test or Wilcoxon signed-rank sum test was performed, depending on the variable normality, with a 95% confidence level.
RESULTS
Of the 171 enrolled participants, 59 were included in the study (mean age, 47.5±12.6 years); 43 were women (72.8%). Eighteen patients (30.5%) had hypertension, and 17 (28.8%) had dyslipidemia.
Ten patients (16.9%) had type 2 diabetes mellitus. Among included participants, 18.6% were overweight and 62.6% had some degree of obesity (23.7% had grade 1 obesity). Seventeen patients had hypothyroidism (28.8%). Table 1 shows baseline characteristics of the study participants.
Table 1
Baseline characteristics of the study participants (n=59)
| Variable | n | % |
|---|---|---|
| Female sex | 43 | 72.88 |
| Age, years (mean ±SD) | 47.5±12.6 | |
| Overweight | 11 | 18.6 |
| Grade 1 obesity | 14 | 23.7 |
| Grade 2 obesity | 11 | 18.6 |
| Grade 3 obesity | 12 | 20.3 |
| Type 2 diabetes mellitus | 10 | 16.9 |
| Smoking | 1 | 1.7 |
| Dyslipidemia | 17 | 28.8 |
| Hypertension | 18 | 30.5 |
| Peripheral arterial or venous disease | 5 | 8.5 |
| Pacemaker | 3 | 5.08 |
| Hypothyroidism | 17 | 28.8 |
| Cancer | 4 | 6.8 |
| Bariatric surgery | 2 | 3.4 |
| Depression | 10 | 16.9 |
| Hematologic disease | 3 | 5.1 |
| Neurologic disease | 5 | 8.5 |
| Rheumatic disease | 4 | 6.8 |
| Regular medication | ||
| Beta-blockers | 9 | 15.3 |
| Oral antidiabetic agents | 10 | 16.9 |
| Antihypertensive agents | 15 | 25.4 |
| Lipid-lowering agents | 16 | 27.1 |
| Hormone replacement therapy and/or vitamins | 22 | 37.3 |
| Antidepressant agents | 11 | 18.6 |
| Benzodiazepines | 6 | 10.2 |
| Antiplatelet agents | 2 | 3.4 |
| Diuretics | 4 | 6.8 |
SD: standard deviation
After implementation of the 21-Day Plan, a significant reduction was observed in the following parameters: body mass index from 36.3 to 35.5 kg/ m2 (p<0.001), total cholesterol from 191.5 to 163.6 mg/dL (p<0.001), LDL-C from 130.7 to 107.6 mg/ dL (p<0.001), triglycerides from 145.5 to 112.5 mg/ dL (p<0.001), the atherogenic index from 4.2 to 3.7 (p<0.001), and hs-CRP from 4.2 to 2.3 mg/dL (p<0.001). Anthropometry and laboratory measurements are shown in Table 2.
Table 2
Anthropometric and laboratory parameters of participants pre- and post-intervention
| Pre-intervention | Post-intervention | ||||||
|---|---|---|---|---|---|---|---|
| n | Mean | SD | n | Mean | SD | p-value | |
| Body mass index, kg/m2 | 49 | 36.3 | 8.9 | 43 | 35.5 | 8.3 | <0.001 |
| Uric acid, mg/dL | 33 | 5.5 | 1.9 | 22 | 5.0 | 1.4 | 0.057 |
| hs-CRP, mg/dL | 40 | 4.2 | 3.3 | 39 | 2.3 | 2.1 | <0.001 |
| Hematocrit, % | 56 | 41.0 | 3.7 | 52 | 40.9 | 3.5 | 0.257 |
| Hemoglobin, g/dL | 56 | 13.3 | 1.5 | 52 | 13.4 | 1.2 | 0.127 |
| Leukocytes, thousand/μL | 56 | 6.6 | 1.5 | 52 | 6.5 | 1.7 | 0.113 |
| Total cholesterol, mg/dL | 59 | 191.5 | 43.4 | 58 | 163.6 | 33.6 | <0.001 |
| HDL cholesterol, mg/dL | 57 | 46.5 | 9.9 | 58 | 44.5 | 9.3 | 0.020 |
| LDL cholesterol, mg/dL | 59 | 130.7 | 45.0 | 59 | 107.6 | 35.0 | <0.001 |
| Triglycerides, mg/dL | 58 | 145.5 | 74.7 | 59 | 112.5 | 54.9 | <0.001 |
| Triglyceride/HDL ratio | 57 | 3.4 | 2.2 | 57 | 2.6 | 1.5 | 0.029 |
| Atherogenic index | 57 | 4.2 | 1.2 | 57 | 3.7 | 0.9 | <0.001 |
| Blood glucose, mg/dL | 56 | 100.5 | 27.9 | 55 | 96.4 | 15.6 | 0.041 |
| Creatinine, mg/dL | 52 | 0.78 | 0.20 | 51 | 0.7 | 0.13 | 0.187 |
| Urea, mg/dL | 41 | 29.2 | 11.3 | 46 | 25.2 | 9.6 | 0.016 |
| Vitamin B12, pg/mL | 43 | 632.5 | 622.8 | 9 | 365.5 | 252.8 | 0.813 |
| Vitamin D, ng/mL | 45 | 28.8 | 11.2 | 9 | 24.1 | 6.4 | 0.877 |
| Homocysteine, μmol/L | 29 | 7.9 | 2.5 | 14 | 9.2 | 1.9 | 1.000 |
| Glycated hemoglobin, % | 27 | 5.7 | 1.15 | 19 | 5.9 | 1.2 | 0.030 |
| Insulin, IU/mL | 29 | 18.9 | 12.07 | 23 | 24.9 | 19.2 | 0.646 |
hs-CRP = high-sensitivity C-reactive protein
Among the 41 participants with complete measurements pre- and post-intervention, cardiovascular risk according to the WHO risk score was low in 68.3%, moderate in 4.9%, high in 19.5%, and very high in 7.3% before implementation of the 21-Day Plan. After implementation of the plan, 4 patients moved from high to moderate risk: the high-risk category decreased to 9.8%, and moderate risk increased to 14.6%; these changes were not statistically significant (p=0.351). Table 3 summarizes cardiovascular risk classification.
DISCUSSION
In light of the study objectives and of previous research conducted by pioneers and organizations in the field of LM (20), based on the results obtained, we can state that a plant-based diet combined with regular physical activity positively impacts on physical health. (21)
Specific macro- and micronutrients within a predominantly plant-based dietary pattern help reduce low-density lipoprotein cholesterol (LDL-C). It has been shown that, with appropriate diet and lifestyle changes, approximately 80% of premature cardiovascular mortality may be prevented. (22)
Despite the ongoing controversy regarding the role of elevated triglycerides as an independent cardiovascular risk factor, epidemiological, clinical, and
pathophysiological evidence indicate that, particularly in patients with insulin resistance, triglycerides are a key etiopathogenic factor in the process related to the development of atherosclerosis and cardiovascular disease. (23)
Regarding the atherogenic index, a recent clinical study published in January 2024 demonstrated that it may serve as an effective marker of future cardiovascular events in the general population, including patients with and without diabetes, and that its monitoring and management may provide additional cardiovascular benefits even in individuals without traditional risk factors. (24)
Obesity has been associated with alterations in hemodynamic, autonomic, and hormonal pathways, resulting in a spectrum of cardiovascular changes, from subclinical structural heart abnormalities to overt heart failure. (25)
A major study collected individual-level data from 1 518 028 subjects from 112 cohort studies conducted in eight geographic regions, and assessed five cardiovascular risk factors: body mass index, systolic blood pressure, non-HDL cholesterol, current smoking, and diabetes, because of their impact on cardiovascular disease (CVD) and all-cause mortality. The five modifiable risk factors accounted for a population-attributable fraction of CVD of 57.2% in women and 52.6% in men and a population-attributable fraction of allcause mortality of 22.2% in women and 19.1% in men, with elevated systolic blood pressure being the leading contributing factor. (26)
Among the available inflammatory biomarkers, hsCRP is an independent and significant risk marker of ischemic cardiovascular disease, as it plays a vital role in atherogenesis. Inhibition of hs-CRP might be an innovative, effective, and safe therapy for the treatment of ischemia and myocardial and cerebral infarctions (27,28) .
Finally, regarding the close relationship between psychological health, well-being, and the mind-heart-body connection, this topic warranted a specific 2021 AHA statement, which emphasized the importance of considering psychological health in the assessment and management of patients with or at risk for CVD. (29)
Based on the scientific evidence and the results obtained regarding reductions in BMI, total and LDL cholesterol, triglycerides, atherogenic index, hs-CRP, and overall cardiovascular risk, we highlight the strengths of this study and its potential for systemic and long-term application.
As main limitations, we should note that not all blood pressure and laboratory measurements were obtained both pre- and post-intervention, partly because some consultations were virtual and some patients without medical coverage were unable to complete the laboratory tests. The intervention lasted 21 days, which may have influenced the absence of statistical significance in the variation of estimated long-term cardiovascular risk. An extended follow-up methodology has not yet been developed to verify adherence to lifestyle changes and the persistence of these outcomes.
CONCLUSIONS
The 21-Day Plan demonstrated the short-term benefit of a plant-based diet and the implementation of regular physical activity, psychological and spiritual support for stress management and emotional support on the studied anthropometric and laboratory parameters, which directly impacted on overall cardiovascular risk.
Conflicts of interest
None declared.
(See authors' conflict of interests forms on the web).