The Effect of Dietary Patterns on Vascular Aging Using the Brachial–Ankle Index

1. Introduction

In modern societies, life expectancy has increased significantly, leading to a higher prevalence of diseases associated with aging, such as cardiovascular diseases [1,2,3]. Specifically, the study of vascular aging is essential to find effective preventive measures [4]. One of the main indicators of vascular aging is arterial stiffness [5]. Among the most common ways to measure arterial stiffness is pulse wave velocity (PWV) [3] which assesses the speed with which a pulse wave travels through the arteries; this velocity increases as blood vessels become stiffer so that higher PWV is associated with higher cardiovascular risk [2]. Among the indices that evaluate PWV is the brachial-ankle index (ba-PWV) which measures the velocity of blood displacement between the brachial artery and the tibial artery using an oscillometric method; it is a simple, non-invasive measurement of peripheral arterial stiffness, is considered a good indicator of vascular health [3,6] and shows a strong correlation with age [3]. Knowing the state of vascular health in the adult population is of vital importance since any dysfunction can have harmful effects on health [6].

The study of vascular aging also focuses on preventing or slowing down the negative effects, the objective being to preserve health and vitality, these concepts giving rise to the term “healthy aging” [4]. Early diagnosis and timely therapeutic interventions are the key to success in delaying or preventing aging [3,7]. To promote healthy aging, there are different strategies such as implementing regular physical exercise [8,9], controlling risk factors [10] or maintaining healthy eating habits [11,12,13], especially with suboptimal diets and lifestyles [9,14,15]. This has been reflected in the literature where a comprehensive lifestyle intervention over 30 years was associated with a reduction of risk factors by 80% [10]. It is estimated that about 11 million premature deaths can be attributed to unhealthy dietary factors [16]. Combining diet with other healthy lifestyles could increase life expectancy by 8 to 10 years [14].

Diet seems to have a close relationship with healthy aging; in particular, adherence to the Mediterranean diet (MD) [17] may be associated with a lower cardiovascular risk [18]. The MD [17] exhibits dietary patterns typical of populations located near the Mediterranean Sea, associated with olive-growing areas. In addition, it is associated with decreased rates of chronic diseases, especially cardiovascular and metabolic diseases associated to a greater extent with obesity, which influences a longer life expectancy [13,19]. This diet is characterized by a high consumption of olive oil and plant foods (vegetables, legumes, potatoes, fruits, bread and other cereals, seeds and nuts) and consumption of seasonal, fresh and minimally processed products. It also recommends a moderate consumption of dairy products such as yogurts and cheeses, fish and a moderate-low consumption of poultry. Regarding eggs, no more than 4 per week are recommended [17]. Regarding caloric intake of fats, MD should not exceed 30% of intake, with saturated fats accounting for 8-10% [20,21]. Therefore, lifestyle factors such as diet can modify the aging process [19,22]. MD is considered to be one of the healthiest diets, highlighting its influence in improving vascular aging [1,13].

Good nutrition, lifestyles, and physical activity are the pillars that help to have a healthy aging [1]. Therefore, the aim of this study is to analyze the association between adherence to the MD with vascular aging estimated with ba-PWV and differences by sex in a sample of a Caucasian population without a history of previous cardiovascular disease.

2. Materials and Methods

2.1. Study Design

Descriptive and observational cross-sectional study. The data analyzed correspond to the data recruited in the MARK [23] (NCT01428934), EVIDENT [24] (NCT0108308) and EVA [25] (NCT02623894) studies.

2.2. Ethical Considerations

The three studies selected have been approved by the ethics committee of the Salamanca area. The MARK study [23] with code PI10/02043, the EVIDENT study [24] with code PI83/06/2018 and the EVA study [25] with codes PI15/01039 and PI20/10569. The objectives of the study were explained and participants signed consent before being included in the studies. The norms established in the Declaration of Helsinki and the WHO standards for observational studies were always followed. Data confidentiality was guaranteed throughout the process.

2.3. Study Population

The MARK study [23] is a prospective multicenter cohort study that included 2511 subjects from 6 health centers in 3 autonomous communities. It was conducted between July 2011 and June 2013.

The EVIDENT study [24] was conducted between the months of January 2014 and September 2016 with a follow-up period of 12 months. It is a randomized, controlled, multicenter clinical trial with 2 parallel groups that included a sample of 1104 subjects recruited in primary care.

In the EVA study [25], the population was recruited in 5 health centers between June 2016 and November 2017. From the total population of 43946 subjects, 100 subjects were selected in each decade being 50% male and 50% female following the inclusion and exclusion criteria established in a previous study [25]. The final sample was 501 subjects.

The subjects were selected by random sampling in the general consulting population between 35 and 75 years of age. Figure 1 shows the subjects included and excluded from each of the 3 studies.

2.4. Variables and measuring Instruments

2.4.1. Vascular Aging

The following steps were followed to define vascular aging. First, the values established by the EVA Group as cut-off points estimated with the ba-PWV for both men and women were taken into account [26]. Subjects with values ≤ 25th percentile were classified as HVA, subjects with values between 25th percentile and 75th percentile were classified as NVA and subjects with values ≥75th percentile were classified as EVA. And second, subjects diagnosed with diabetes who belonged to the HVA group were reclassified as NVA [27].

2.4.2. Mediterranean Diet

To determine adherence to the MD, we used the questionnaire validated in the Spanish population, which was used in the PREDIMED study [28]. The Mediterranean Diet Adherence Screener (MEDAS) questionnaire consists of 14 items, 12 of which ask about the frequency of food consumption and 2 of which ask about the eating habits of the Spanish population. Each of the questions can be scored with 0 or 1 point, the final score ranges from 0 to 14 points and adherence to the MD is considered if the score is higher than the median (7 or more points).

To obtain the score: a) consume olive oil as the main cooking fat; b) consume four or more tablespoons of olive oil daily (one tablespoon = 13. 5g); c) consume two or more servings of vegetables; d) consume three or more pieces of fruit; e) consume less than one serving of red or processed meat; f) consume less than one serving of animal fat; g) consume less than one 100ml cup of sweetened beverages; h) eat white meat in greater proportion than red meat; i) consuming seven or more glasses of wine per week; j) consuming three or more servings of legumes; k) consuming three or more servings of fish; l) consuming three or more servings of nuts or dried fruits; m) consuming two or more servings of fried foods and n) consuming less than two baked goods were evaluated with 1 point [28].

2.4.3. Vascular Function

The function was estimated using the brachial-ankle index (ba-PWV) with the VaSera VS-1500® device (Fukuda Denshi, Tokyo, Japan).

The following equation was used to estimate ba-PWV: ba-PWV=((0.5934×height (cm)+14.4724))/tba, where tba is the transmission time of the waves to the ankle [29]. A value less than 0.9 of ba-PWV [30]. For this study, the mean value of the two extremities of ba-PWV was taken into account.

2.4.4. Anthropometric Measurements

Weight, height and blood pressure were taken into account. Hypertension was considered present if the subjects were taking antihypertensive drugs or if their blood pressure values were higher than 140/90 mmHg. They were considered to have type 2 diabetes mellitus if they were taking hypoglycemic agents or if their fasting plasma glucose values were higher than 126mg/dl or higher than 6.5% in the case of HbA1c. Dyslipidemia was considered present if they were taking lipid-lowering drugs or had fasting total cholesterol values higher than 240 mg/dL, low-density lipoprotein cholesterol (LDLc) higher than 160 mg/dL, high-density lipoprotein cholesterol (HDLc) lower than 40 mg/dL in men and lower than 50 mg/dL in women, or triglyceride values higher than 150 mg/dL. Obesity was defined using a BMI value above 30 kg/m2 [31].

In addition, venous blood samples were taken from all participants between 8:00 a.m. and 9:00 a.m.

All measurements were performed by primary care professionals.

2.5. Statistical Analysis

Continuous variables are presented as means ± standard deviations and categorical variables as numbers or percentages. Chi-square tests for percentages and Student's t-tests for continuous variables were used to compare men and women. The ANOVA test was used to compare means between the three aging groups (EVA, HVA, NVA). Multinomial logistic regression was performed to analyze the association between adherence to MD and arterial stiffness, measured through ba-PWV, categorized into three levels according to the 25th and 75th percentile cut-off points. MD was assessed using a numerical scale and was included as a main predictor variable. Regression was adjusted for age, sex, and consumption of antidiabetic, lipid-lowering, and hypertensive drugs. Age, sex, and consumption of lipid-lowering, hypolipidemic, antihypertensive, and lipid-lowering drugs were used as adjustment variables. All analyses were performed by gender and globally. SPSS Statistics for Windows, version 28.0 (IBM Corp, Armonk, NY, USA) was used. A value of p<0.05 was considered as the limit of statistical significance.

3. Results

3.1. Baseline Characteristics

The total sample consisted of 3437 subjects, 500 subjects belonged to the EVA study, 2505 subjects participated in the MARK study and 432 belonged to the EVIDENT study (Figure 1). 43% of the sample consisted of women (n=1468) and the mean age was 60.15±9.55 (60.09±9.71 for women and 60.20±9.43 for men) p=0.728. The score obtained in MD was 5.82±2.03 overall (6.03±1.98 for women and 5.66±2.06 for men) p<0.001. The mean ba-PWV value was 14.38±2.71 (14.24±2.89 for women and 14.49±2.56 for men) p=0.007 (Table 1). This table also shows the values of the drugs used in the treatment of dyslipidemia, diabetes mellitus and hypertension, in addition to the values obtained for cardiovascular risk factors in the overall population and by sex.

3.2. Characteristics of the Subjects in Relation with Vascular Aging and Mediterranean diet

Table 2 shows the differences in the total sample in the MD, cardiovascular risk factors and drugs used in the subjects according to their degree of aging. 14% of the sample (n=475) was classified as HVA; 45% (n=1559) as NVA and the remaining 41% (n=1403) were classified as EVA (Figure 2). The mean age for subjects in the HVA group was 59.39±10.34, (60.28±9.30 for men and 57.93±11.73 for women); for the NVA group it was 60.33±9.78, (60.34±9.60 for men and 60.31±10.04 for women) and for the EVA group it was 60.22±8.98, (60.02±9.29 for men and 60.47±8.59 for women). For the ba-PWV variable, lower velocity was observed for the HVA group with values of 11.60±1.34 (11.91±1.17 for men and 11.08±1.45 for women) than in the NVA groups with values of 13.45±1. 69 (13.59±1.43 for men and 13.25±1.99 for women) and EVA with values of 16.36±2.57 (16.52±2.49 for men and 16.18±2.67 for women) being significant in all cases (p<0.001).

Table 3 shows the differences by sex of the sample in MD, cardiovascular risk factors and drugs used in the subjects according to their degree of aging.

Figure 2 shows the classification according to the degree of aging and origin of the subjects in each of the three studies

3.3. Association between ba-PWV y MD overall and by sex. Multinomial logistic regression.

A multinomial logistic regression was performed to determine the association between ba-PWV and MD, finding a significant relationship both globally and by sex. Globally, a strong association was observed between HVA and NVA (OR=1.751, 95% CI:1.411-2.174, p<0.001), as was the association between HVA and EVA (OR=1.501, 95% CI:1.295-1.740, p<0.001). Women showed an even stronger association between HVA and NVA (OR=2.055, 95% CI:1.456-2.901, p<0.001), and also with EVA (OR=1.413, 95% CI:1.124-1.776, p=0.003). The association was also significant for men, although slightly more moderate: HVA vs. NVA (OR=1.551, 95% CI:1.175-2.047, p=0.002), and HVA vs. EVA (OR=1.549, 95% CI:1.275-1.882, p<0.001) (Table 4).

4. Discussion

This study shows the association between adherence to MD and vascular aging analyzed with the brachial-ankle index (ba-PWV) in a sample of 3437 Caucasian subjects. The most important results found in this work are a strong positive association between HVA and NVA and between HVA and EVA both overall and by sex.

In agreement with a recent review and meta-analysis [32] the MD score was higher in women than in men.

On the other hand, there are several studies showing the benefits of the MD. Among them we can mention the NU-AGE study, with 1296 participants, evaluated whether the MD specifically targeting people over 65 years of age could be effective in shifting the intake of older adults towards a healthy diet [33]. Similarly, Jennings et al. in 2019 found that MD was effective in improving cardiovascular health with significant reductions in blood pressure and arterial stiffness [34].

The study by Assmann et al. with a sample of 3012 participants aged 45 to 65 years investigated the association between adherence to MD in midlife and healthy aging finding that high adherence to MD is favorable in midlife for maintaining good general health during aging [35]. These works are in line with the results shown in this work, finding in the multinomial logistic regression results of the present study show that adherence to MD is associated with lower arterial stiffness, evidenced by the values obtained in all comparisons. This association was observed to a greater extent among individuals belonging to the HVA and NVA groups and between HVA and EVA. Moreover, the association was greater in women especially between HVA and NVA (OR=2.055 vs OR=1.551 in men). It can be deduced that MD is not only associated with a more favorable risk profile but may also be a crucial factor in improving vascular health in the Spanish adult population. Although the values were slightly better in women, significant associations were observed in both sexes, which suggests that better adherence to MD may act as a protector against vascular aging.

It should be noted that studies have also been found in the literature that implement different strategies with the aim of improving health by modifying lifestyles, including adherence to MD, such as adding a yoga program combined with MD, obtaining good results in the intervention group [36] or including new technologies such as a smartphone and smartband, although in the latter case there were no changes in lifestyle related to physical activity or eating habits [37]. More studies are needed to specify the associations between the different strategies that are carried out, as well as to determine to what extent they are effective or to establish the superiority of some over others in improving vascular health in this population.

The present study has a number of limitations. Firstly, the sample is made up of patients without previous cardiovascular disease, so the results cannot be extrapolated to other types of population. On the other hand, the sample analyzed is part of three studies in which the percentage of subjects included is not the same, since the MARK study contributed the greatest number of subjects (2505) compared to EVA (501) or EVIDENT (432). On the other hand, the data were extracted at a single point in time, so it is a cross-sectional study that does not allow us to know cause and effect. However, it is worth highlighting the strengths of the study: it is a study with a large sample recruited from primary care clinics in Spain that investigated adherence to MD in the population of subjects aged 35 to 75 years to determine its association with healthy aging. The study has had a protocolized design that ensures the correct measurement and evaluation of the subjects. The findings of this study underscore the relevance of healthy vascular aging in the prevention of vascular dysfunction, with implications for both public health and gender-differentiated intervention strategies.

5. Conclusions

The results of this study indicate that greater adherence to MD is associated with healthier vascular aging. This suggests the importance of promoting MD as a public health intervention strategy to prevent vascular aging and its consequences.