Physical activity in premenopausal women with asymptomatic peripheral arterial disease

: Physical activity is considered very useful in the prevention of cardiovascular disease. The present study aims to evaluate the role of physical activity in women with high adherence to a Mediterranean diet and its correlation with asymptomatic atherosclerosis. A group of 425 premenopausal women (mean age 48 ± 9 years) was evaluated. They completed the International Physical Activity Questionnaire (IPAQ) developed by the World Health Organization, validated for the Italian population, to assess the degree of physical activity participation. The questionnaire classified physical activity as vigorous intensity, moderate intensity, and walking. Diet was assessed by a self-administered food frequency validated questionnaire completed by an interviewer-administered at 24 h diet recall. As a marker of preclinical evaluation we measured ankle-brachial index (ABI). We observed that level of physical activity was inversely associated with ABI suggesting a protective effect on preclinical atherosclerosis. Women who belonged to the highly active group (health-enhancing physical activity) were also those who had a greater adherence to the Mediterranean diet and had a lower body mass index. HEPA active women showed less instrumental signs of preclinical peripheral atherosclerosis. We can suggest that physical activity plays an important role in the prevention of atherosclerosis in premenopausal women.


Letter to the editor
Lifestyle, including nutrition and physical activity, plays an important role in the development of cardiovascular disease (CVD) and may contribute to the geographic and sex variability in CVD morbidity and mortality. 1,2Regular exercise in combination with specific dietary patterns (i.e.Mediterranean pattern) may have a beneficial effect on the cardiovascular system through the modulation of the oxidation process. 3,4e ATTICA study had clearly shown that highly active people who exercise several days per week enjoyed greater protection from the oxidative process because of a higher total antioxidant capacity (TAC) level. 5 also reported that women with high adherence to a Mediterranean diet are less likely to develop preclinical atherosclerosis compared with women with a low adherence. 4he present study aims to evaluate the role of physical activity in women with high adherence to a Mediterranean diet and its correlation with asymptomatic atherosclerosis.

Methods
A retrospective analysis on a group of 650 women (age range 45-54 years) was performed.Patients were refered to our clinic from general practitioners for screening and prevention of CVD.We selected women only if they were free of symptoms of peripheral arterial disease (PAD), had ABI evaluation and a complete nutritional assessment.We excluded participants with a previous history of cardiovascular disease (ischemic heart disease heart failure and stroke), those who did not complete a questionnaire, and those who did not undergo ABI evaluation and who did not sign the consent (Figure 1 supplemental material, http://links.lww.com/JCM/A141).The group of women who completed the physical activity questionnaire included 425 women (mean age 48 AE 9 years).
Study was approved by the Local Ethical Review Board and participants signed an informed consent.

Data collection
Nutritional status was assessed by measuring weight, body mass index (BMI), waist circumference and waist-to-hip ratio. 6e prevalence of nutritional parameters was assessed by a self-administered food frequency questionnaire (FFQ) with 116 items and completed by an interviewer-administered 7-day diet recall questionnaire on the day of first visit. 6e food list in the FFQ was Italianized, and foods commonly eaten in the Emilia Romagna region of Italy were added.For each food class, color photographs of three different portions were displayed.Portion sizes were chosen according to many years of experience in dietary surveys in various parts of Italy. 6od frequency was evaluated using three categories: daily, weekly and monthly and from one to six times (i.e.once a day, three times a week) and was integrated with specific questions on changes in nutrition habits and lifestyle within the last year.The Mediterranean score was calculated according to Panagiotakos. 6A dietician, using a database system, computed food and nutrient intakes from FFQ and dietary recall.The nutrient database was compiled from food composition tables.

Physical activity
We utilized the International Physical Activity Questionnaire (IPAQ) developed by the World Health Organization (WHO) and validated for the Italian population to assess the degree of physical activity participation.The questionnaire classified physical activity as vigorous intensity, moderate intensity and walking, and further obtained information of time and frequency. 7IPAQ categories for health, from the IPAQ-scoring protocol (www.ipaq.ki.se): health-enhancing physical activity (HEPA) (reaching recommendations for health-enhancing physical activity) active: vigorous activity at least 3 days per week, totaling at least 1500 MET min per week, or at least 7 days per week of any combination of walking, moderate-intensity or vigorous activities, totaling more than 3000 MET min per week.Minimally active: not HEPA active, but at least 3 days per week of vigorous activity of at least 20 min per day, or at least 5 days per week of moderate-intensity activity or walking at least 30 min per day, or at least 5 days per week of any combination of walking, moderate-intensity, or vigorous activities, totaling at least 600 MET min per week.Insufficiently active: not belonging to either of the above categories.Total METs (continuous score from the IPAQ-scoring protocol) were calculated as follows: (daily minutes of walking Â days per week with walking Â 3.3) þ (daily minutes of moderateintensity activity Â days per week with moderate-intensity activity Â 4.0) þ (daily minutes of vigorous activity Â days per week with vigorous activity Â 8.0).The MET values were derived from the IPAQ validity and reliability study. 8gorous activity METs were calculated from the equation daily minutes of vigorous activity Â days per week with vigorous activity Â 8.0.

Ankle brachial index measurement
All patients underwent ABI measurement.The ABI is a simple, noninvasive test, measuring the systolic blood pressure (SBP) from both brachial arteries and from both the dorsalis pedis and posterior tibial arteries after the patient has been at rest in the supine position for 10 min by using a Doppler device.The ABI of each leg is calculated by dividing the higher of the dorsalis pedis pressure or posterior tibial pressure by the higher of the right or left arm blood pressure. 4,9atistical analysis SPSS, V.21.0.1 (SPSS Inc, Chicago, Illinois, USA) was used for statistical analysis.Results are presented as mean AE standard deviation (SD) or frequency expressed as a percentage.
To study the association of physical activity with PAD, we used Cox proportional hazards regression analysis.For these analyses, physical activity was used as continuous and categorical (HEPA activity, minimally active, insufficiently active) variables, in order to obtain the best fitting model.We performed analyses in which we first adjusted for age, BMI, smoking, and adherence to a Mediterranean diet (model 1); and additionally for total cholesterol, HDL cholesterol, SBP, and high sensitivity C-reactive protein (hs-CRP) (model 2).
In interaction analysis, P interaction less than 0.05 was considered to indicate effect modifiers on the association of physical activity with ABI.

Results
The descriptive results of IPAQ are shown in Table 1.The MET-minute-per-week distributions were extremely skewed to the right; however, the proportion of women scored as HEPA active was low.The mean Mediterranean diet score was 32.6 AE 3.3 (median score was 30.9).The IPAQ Total MET-min per minute was 4970 AE 4323 and the IPAQ Vigorous MET-min per minute was 2115 AE 2196.The associations between IPAQ groupings and Mediterranean diet were consistent, regardless of the way IPAQ was used (HEPA categories, total METs, vigorous): almost all outcome variables showed increasing adherence to a Mediterranean diet from the first (least active) through the fourth group.
Table 2 shows association between clinical characteristics and physical activity (linear regression analysis).
Table 3 illustrates the association of physical activity with ABI value after adjustments for age, BMI, smoking, and adherence to a Mediterranean diet (model 1) and additionally for total cholesterol, HDL cholesterol, SBP and hs-CRP (model 2).

Discussion
This retrospective analysis was performed to evaluate the relationship between physical activity and asymptomatic PAD in premenopausal women.We observed that our women population was less likely to perform high levels of physical activity.We reported that women who belonged to the highly active group (HEPA active) were also those who had a greater adherence to a Mediterranean diet and had a lower BMI.
In addition, physical activity was inversely associated with preclinical atherosclerosis suggesting a protective effect.The effect of exercise on the prevention of atherosclerosis is not so clear, and because of the multifactorial pathophysiology of plaque, it is plausible that the exercise effects might be modulated by other important factors like diet, antioxidants intake and smoking.
The current recommendation for physical activity in adults and older adults is at least 150 min of moderate-intensity physical activity per week. 10This is based on a number of systematic reviews and consensus statement, consistently identifying 150 min per week as providing considerable health benefits, including reduced all-cause mortality, reduced risk factors for chronic diseases, improved cardiovascular fitness and quality of life. 10,11Increasing levels of physical activity was associated with a lower risk of mortality and cardiovascular disease.For women in high-income countries in the global burden of disease study, the estimated population attributable risk for mortality was 14% for smoking, 8% for overweight, 5% for physical inactivity, 4% for low fruit and vegetable intake and À3% for alcohol use. 12Mokdad et al. 13 estimated that the population attributable risks for US mortality in 2000 was 18% for tobacco, 15% for poor diet and physical inactivity, and 3.5% for excess alcohol consumption.
The Mediterranean diet is characterized by a high intake of antioxidants from fruit and vegetables and was associated with a lower incidence of atherosclerosis in several studies. 14,15e great majority of articles, however, underline the role of a healthy lifestyle that included both a good diet and high level of physical activity.
Diet and physical activity were evaluated in many different population, that is, in postmenopausal women. 16For menopause management, it is recommended that lifestyle changes as a primary modality of care including exercise and a diet rich in calcium, fiber, and low in fat, especially saturated fats 1,16 Dietary calcium intake and physical activity have a major impact on the bone health in postmenopausal women.Physical activity is defined as any bodily movement produced by skeletal muscle that requires energy expenditure, although, it is known that exercise can be more effective. 17,18Physical activity needs to be regular and sustained to confer the largest cardiovascular benefits.However, compared with being inactive over time, all patterns of physical activity change had lower all-cause mortality risk estimates. 19e ATTICA study suggested that regular exercise in combination with the Mediterranean dietary pattern may have a beneficial effect on the cardiovascular system through another pathophysiological mechanism, that is, their ability to modulate the oxidation process.Specifically, they found that highly active people who exercise several days per week had higher levels of TAC and that the degree of physical activity was positively correlated with TAC. 5 In a previous article, we found that fruit and vegetable consumption was inversely associated with preclinical atherosclerosis in women. 20A diet rich in fruit and vegetables leads to a high intake of carotenoids and vitamins.Because of their antioxidant properties, carotenoid, and vitamins prevent the oxidation of cholesterol and other lipids reducing cardiovascular damage.Physical activity has been shown to greatly improve cardiovascular function, in part through the improved bioavailability of nitric oxide, enhanced endogenous antioxidant defense and a lowering of the expression of ROS-forming enzymes. 21,22We suppose that physical activity modulates endothelial response to lipids and a synergy with a healthy diet such as a Mediterranean diet improves this positive effect.Endothelial dysfunction, which is a central mechanism leading to CVD and the redox switch could be modulated by physical activity (that acts directly on endothelium) and dietary factors reducing the risk of CVD onset.

Limitation of the study
The evaluation of physical activity was obtained using a validated self-administered questionnaire.It is well known that population-level assessments of physical activity overestimate the total amount of physical activity, and perceived intensity of physical activity may vary according to individual fitness or obesity level. 23In recent years, several apps have been developed in order to objectively measure the physical activity performed by an individual.Further studies based on accelerometers and phone apps will increase our knowledge.In conclusion, we can suggest that physical activity plays an important role in the prevention of atherosclerosis in premenopausal women.

Table 1 International
Physical Activity Questionnaire categories

Table 2
Clinical characteristics of patients and association with physical activity (linear regression analysis) BMI, body mass index; hs-CRP, high sensitivity C-reactive protein; SBP, systolic blood pressure.