Sun Exposure and Intima-Media Thickness in the Mexican Teachers' Cohort Study

Abstract

Objective:

To determine whether long-term sun exposure has a protective role in subclinical cardiovascular disease in adult Mexican women.

Materials and Methods:

We conducted a cross-sectional analysis of a sample of women from the Mexican Teachers' Cohort (MTC) study. Sun exposure was assessed in the MTC 2008 baseline questionnaire, in which women were asked about their sun-related behavior. Vascular neurologists measured carotid intima-media thickness (IMT) using standard techniques. Multivariate linear regression models were used to estimate the difference in mean IMT and 95% confidence intervals (95% CIs), according to categories of sun exposure and multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% CIs for carotid atherosclerosis.

Results:

The mean age of participants was 49.6 ± 5.5 years, the mean IMT was 0.678 ± 0.097 mm, and the mean accumulated hours of weekly sun exposure were 2.9 ± 1.9. Prevalence of carotid atherosclerosis was 20.9%. Compared with women in the lowest quartile of sun exposure, women in the highest quartile had lower mean IMT, but this was not significant in the multivariable adjusted analysis. (Adjusted mean % difference: −0.8; 95% CI: −2.3 to 0.8). The multivariate adjusted ORs of carotid atherosclerosis were 0.54 (95% CI: 0.24–1.18) for women who were exposed 9 hours. For women who denied regular sunscreen use, those in the higher exposure category (9 hours) had lower mean IMT compared with those in the lower category (multivariable-adjusted mean % difference = −2.67; 95% CI: −6.9 to −1.5).

Conclusions:

We observed that cumulative sun exposure was inversely associated with IMT and subclinical carotid atherosclerosis. If these findings are further replicated and seen for other cardiovascular outcomes, sun exposure could be an easy, affordable strategy to lower overall cardiovascular risk.

Introduction

According to the Global Burden of Disease (GBD) Study 2017, noncommunicable diseases (NCDs) contribute to 73.4% of total deaths, globally.¹ Within the NCDs, cardiovascular disease (CVD) is the number one cause of death. In Mexico, NCDs represent 77% of total adult deaths, with CVD accounting for almost a quarter (24%) of these deaths.¹

Previous studies^2
–4 have suggested that cardiovascular health differs according to weather, season, and other environmental factors. Ultraviolet (UV) radiation from sun exposure has been widely established as a risk factor for skin cancer, especially melanoma. Consequently, public health recommendations focus on avoidance of excessive sun exposure.⁵ However, sun exposure is the main source of vitamin D (VD) in humans because photons are required to convert 7-dehydrocholesterol in the epidermis into provitamin D_3. ⁶ Despite this fact, few studies have evaluated how sun exposure affects cardiovascular health. In this sense, some evidence from ecological studies have found an inverse relationship between sun exposure and blood pressure or CVD.^7,8

Nevertheless, other mechanisms related to sun exposure have been associated with decreased cardiovascular risk, such as release of nitric oxide in response to nitrite decomposition induced by UVA irradiation.⁹ This nitric oxide release has been shown to decrease both systolic and diastolic pressure that might ultimately decrease cardiovascular risk.¹⁰

Observational longstanding data have shown that there are seasonal differences in blood pressure with higher levels in systolic blood during winter than summer.¹¹ Similar changes have been observed in different latitudes, where places closer to the Equator showing lower systolic blood pressures.¹² Adequate sun exposure could be an easy, affordable strategy to lower cardiovascular risk.

Intima-media thickness (IMT) has been used as a marker of subclinical cardiovascular disease, and it has been shown to correlate with the risk of stroke and myocardial infarction.¹³ Low vitamin D levels have been associated with higher cardiovascular risk in several observational studies^14
–16; however, oral supplementation has not shown a protective effect in clinical trials or in meta-analysis.^17
–19 Thus, our main objective was to determine if long-term sun exposure has a protective role in subclinical cardiovascular disease in adult Mexican women. As an additional analysis, we also evaluated short-term sun exposure and its association with subclinical cardiovascular disease.

Materials and Methods

Study population

We conducted a cross-sectional analysis of a sample of women from the Mexican Teachers' Cohort (MTC) study. The MTC is a prospective study with 115,314 female school teachers aged ≥25 years from 12 geographically and economically diverse states in Mexico. Details of the study design, methodology, and participants' baseline characteristics have been published previously.²⁰

In 2006 and 2008 we invited women to participate and respond a baseline questionnaire on demographic and reproductive characteristics, lifestyle, and medical conditions. Between September 2012 and June 2017, random sample of 4,310 women were invited to participate in an ancillary study on subclinical cardiovascular disease (sCVD). There were seven sites where clinical evaluations took place. Women were eligible if they lived in a 50 km radius from the clinical sites. For the central region of Mexico, clinical evaluations were conducted in Mexico City, whereas for the northern region evaluations were performed in Monterrey, Nuevo León. For the southeastern region of Mexico, we evaluated women in five clinical sites, four of them located in Chiapas (Tuxtla Gutiérrez, San Cristobal de las Casas, Comitán and Tapachula) and one in Yucatán (Mérida).

A total of 2,770 participants (64.2%) chose to participate in the study. Of these, we excluded women with missing data on sun exposure (n = 223) or carotid IMT measurement (n = 282). Women who reported a previous diagnosis of stroke or myocardial infarction were also excluded (n = 8). Finally, a total of 2,257 participants were included in our analysis.

This study was developed and performed according to the Declaration of Helsinki guidelines. The Research, Ethics, and Biosecurity Committee at the National Institute of Public Health (INSP, by its Spanish acronym) evaluated and accepted the study protocol and informed consent forms. Written informed consent forms were obtained from each participant.

Assessment of sun exposure and sunscreen use

In the MTC 2008 baseline questionnaire, women answered questions on their sun-related behavior by reporting their weekly average hours spent outdoors during the school year around midday (solar noon) at four different age periods: 12–18, 25–35, 36–59 and >60 years. Four multiple-choice answers were possible (all in hours): <1, 2–5, 6–8, and >8. Similar questions have been used in previous studies with validated questionnaires to assess sun exposure.^21
–23 Sun exposure for ages 19–24 were not asked in the original questionnaire; therefore these values had to be imputed for all participants. We used the R Package “MICE” (July 27, 2018, Version 3.3.0). The package performs multiple imputations using Fully Conditional Specification. The variables we used to conduct the imputation were site, indigenous background, socioeconomic status, and smoking status.

Evaluation of subclinical carotid atherosclerosis

Carotid IMT is a quantitative marker of vascular injury and increased carotid IMT is a measure of atherosclerotic burden and a predictor of subsequent cardiovascular events.²⁴ Vascular neurologists measured IMT and detected carotid atherosclerotic plaques using a SonoSite™ MicroMaxx™ ultrasound and Asus™ laptop with M'AthStd Software™ (Intelligence in Medical Technologies, Paris, France). Researchers and a senior neurologist (C.C.-B.) with extensive experience in carotid ultrasonography corroborated that study neurologists were appropriately trained and followed standardized procedures. Patients were positioned with their head rotated 0°–30° and IMT was measured between the lumen-intima and media-adventitia interfaces on the far wall of the common carotid artery, at least 5 mm below its end where the carotid bifurcation was visible. Images of a 10-mm arterial segment were used to measure mean IMT for each common carotid artery from which overall mean was calculated.

Measurement of IMT was carried out in each common carotid artery according to the Mannheim Carotid IMD and Plaque Consensus;²⁵ in agreement to this, IMT measurement was conducted in the common carotid artery unless there was plaque in which IMT was measured at the carotid bulb or internal carotid artery. Assessment of plaque was conducted in the common carotid artery because common and internal carotid arteries are homogeneous in structure and hemodynamics.²⁵ If neurologists could not obtain an adequate image, they repeated this procedure on the near wall. Structures protruding into the arterial lumen by ≥0.5 mm or 50% of the surrounding IMT or IMT >1.5 mm were considered an atherosclerotic plaque. Reproducibility was evaluated among 147 women from two different sites and showed high correlations: Intraclass Correlation Coefficient (ICC) = 0.89 (95% confidence intervals [95% CI]: 0.84–0.93) for Chiapas and ICC = 0.92 (95% CI: 0.86–0.96) for Yucatan.

Covariates

We obtained information on covariates based on self-reports from the 2008 baseline questionnaire. Covariates were updated based on information from clinical evaluations whenever possible. Baseline questionnaire included questions regarding indigenous background (defined as either the participant or her parents spoke an indigenous language), physical activity [Metabolic Equivalents of Task (METs/week)], and regular sunscreen use (yes or no). For physical activity, participants were asked how many hours per week they spent on moderate and vigorous recreational and nonrecreational activities. Depending on the intensity of each activity, according to the U.S. Department of Health and Human Services Physical Activity Guidelines for Americans,²⁶ a value of MET was assigned and then multiplied by the hours per week spent on each activity. The total METs were obtained by adding the METs per week per activity.

Eight multiple-choice categories were possible ranging from none to >10 hours/week. The baseline questionnaire also included questions regarding the ownership of seven household assets: telephone, cell phone, internet access, microwave oven, car, computer, and vacuum cleaner. We created a household asset score used as a proxy for socioeconomic status (SES). Then SES score was divided into tertiles to classify women as belonging to low, medium, or high SES. Smoking status was updated with information from the clinical assessment in which women could choose from three categories: never, current, or past smoker.

At the clinical sites, trained personal who used standardized procedures performed anthropometric measurements. Body weight was assessed with an electronic digital scale (Tanita Corp., Arlington Heights, IL) to the nearest 0.1 kg, with participants wearing minimum clothing and no shoes. Height was measured using an electronic digital scale (Seca Corp., Hamburg, Germany) to the nearest millimeter, with barefoot participants standing with their shoulders in a normal position. Body mass index (BMI) was calculated as the weight in kilograms over height in meters squared (kg/m²) and individuals were categorized as normal, overweight, and obese according to World Health Organization (WHO) criteria.

Menopausal status was defined with baseline information on age and reasons for ceasing menstruation for at least 12 continuous months.

Using a validated food frequency questionnaire, a calculated nutrient intake using two food-composition databases: United States Department of Agriculture (USDA) and a local food-composition database compiled for Mexico's National Health and Nutrition Survey allowed us to estimate daily intake of vitamin D.^27,28 Vitamin D supplementation data were collected from the questionnaire as self-report of supplement consumption but it was not considered as a covariate because it does not modify both sun exposure and IMT.

Statistical analysis

Because the options for hours spent outdoors were asked in ranges, women were assigned to one of four categories of hours of sun exposure: 1–3.4, 3.5–6.9, 7–8.9, and ≥9. Our primary exposure was long-term sun exposure. We defined this exposure as the weekly hours spent outdoors at solar noon from age 12 to the clinical examination. Women were then categorized into quartiles of sun exposure according to this average, distribution varied across groups because of the initial distribution of the exposures. This first analysis was prespecified, the rest of the analyses were planned according to data distribution. We also evaluated short-term and age period sun exposure. We defined short-term (recent) exposure as the hours spent outdoors at solar noon at the time when the IMT measurement was made. Women were assigned to one of four categories of sun exposure defined previously.

We also evaluated sun exposure for the four age periods: 12–18, 25–35, 36–59, and older than 60 years. For this exposure women were classified into tertiles because there were very few women in the last quartile. We normalized the measurements of IMT by log-transformation. Carotid atherosclerosis was defined as mean left or right IMT of ≥0.8 mm or the presence of plaque. We used age-adjusted and multivariable-adjusted linear regression models to estimate the percentage difference in mean IMT and 95% CIs according to categories of sun exposure defined previously and used the first category as reference. We used logistic regression models adjusted for age and multiple risk factors to estimate the odds ratio (OR) and 95% CIs for carotid atherosclerosis.

Variables that had an effect both on sun exposure and IMT were selected as confounders, whereas variables that only modified either sun exposure or IMT separately were considered as effect modifiers. Because evidence suggests that individuals from different ethnicities, as well as those who are obese, may have lower circulating levels of vitamin D,^29,30 we therefore explored effect measure modification by conducting stratified analyses by ethnicity (indigenous or not indigenous) and BMI (normal, overweight, and obese). For the most recent sun exposure, we conducted sensitivity analyses excluding women with regular sunscreen use, as it modifies the absorption of UV radiation³¹ and using a stricter definition for carotid atherosclerosis (mean left and right IMT ≥0.8 mm or the presence of plaque).

Menopause has been associated with a faster increase in IMT,³² but we did not consider it to be a confounder because sun exposure was measured through several periods of time including premenopausal ages. All statistical tests were 2-sided, p-value <0.05 was considered significant. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).

Results

Table 1 provides general and sociodemographic characteristics of the 2,257 women included in the analysis. Of those invited, close to 70% chose to participate. Characteristics did not substantially vary between attendees and nonattendees. The mean age of participants was 49.6 ± 5.5 years, and the mean IMT was 0.678 ± 0.097 mm. The overall prevalence of carotid atherosclerosis was 20.9%. The mean accumulated hours of weekly sun exposure were 2.9 ± 1.9 for the whole study population. In addition, according to the quartiles of sun exposure, we observed that subjects in the highest quartile had a lower IMT (0.666), compared with the subjects in the lowest quartile of sun exposure (0.688).

Table 1.

Characteristics of 2,257 Women from the Mexican Teachers' Cohort by Weekly Mean Hours of Sunlight Exposure from Age 12 to Age of Intima-Media Thickness Measurement

	Quartiles of sun exposure
	Q1, n = 563	Q2, n = 564	Q3, n = 618	Q4, n = 512
Median (range) hours of weekly mean hours of sunlight exposure	1 (1–1.4)	1.8 (1.4–2.4)	3.5 (2.4–3.5)	5.2 (3.5–13.2)	p
Age, years^a	50.8(6)	49.8(5)	49.1(5)	48.9 (6)	0.012
Speaks indigenous language^b	10.3	14.4	15.1	14.9	0.314
Highest socioeconomic tertile	53.6	53.6	52.4	48.3	0.016
Teaches at rural site	11.6	13.4	13.2	17.0	0.919
Menopausal	61.4	59.7	53.8	56.5	<0.001
Clinical site
Chiapas	31.6	29.9	25.1	25.9	<0.001
Mexico City	11.0	12.9	15.9	20.0
Monterrey	35.9	30.5	29.1	26.9
Yucatán	21.9	26.6	29.9	27.1
Total intensity exercise, METS/week	27.1(28)	29.9(29)	33.8(29)	44.9(39)	0.587
Total alcohol servings per month	2.1(6)	2.1(3)	1.8(6)	2.1(6)	0.670
Smoking status
Never	67.1	63.3	61.7	62	0.671
Past	23.9	26.7	27.1	27.8
Current	8.9	8.4	10.0	8.4
Intima-media thickness (mm)	0.688 (0.099)	0.686 (0.099)	0.672 (0.093)	0.666 (0.096)	0.011
Diabetes	6.8	10.6	9.6	11.8	0.064
Hypertension	18.9	20.5	18.4	22.1	0.478
Hypercholesterolemia	23.9	26.2	25.7	26.8	0.738
Body mass index, kg/m²
Normal, %	20.5	22.1	22.3	21.5	0.787
Overweight, %	42.3	39.4	41.9	43.0
Obesity, %	37.3	28.5	38.5	35.5
Vitamin D intake, UI, days	158.4(117)	161.7(125)	171.9(141)	175.5(117)	0.197
Vitamin D supplements, %	6.0	2.5	1.8	3.0	<0.001
Regular sun screen use, %	37.5	41.0	36.7	44.3	0.212

Values are given as percentages, mean ± SD, and are adjusted to the age distribution of the study population.

Values are not age adjusted.

Defined as either speaking an indigenous language or having a parent who did.

MET, metabolic equivalents of task; SD, standard deviation.

Compared with women who spend less time under the sun, women with the highest sun exposure category (median 5.2 hours/week) were more likely to teach at rural areas and use sunscreen regularly. Women in the highest category of sun exposure reported higher levels of physical activity but were less likely to be in the highest tertile of the socioeconomic status score relative to women in the referent category. In addition, a slightly higher prevalence of diabetes, hypertension, and hypercholesterolemia was observed among women with the highest sun exposure. We observed a variation in sun exposure according to study site. The proportion of women from Chiapas and Monterrey decreased as the sun exposure increased across quartiles.

Compared with women in the lowest quartile of sun exposure, women in the highest quartile had lower mean IMT (age-adjusted mean % difference = −1.6; 95% CI: −3.0, to −0.01). However, this association was no longer significant when additional confounders were included in the model (multivariable-adjusted mean % difference: −0.8; 95% CI: −2.3 to 0.8). Compared with women in the lowest quartile of sun exposure, the multivariable adjusted ORs of carotid atherosclerosis were 0.89 (95% CI: 0.67–1.21) for women in the second quartile, 0.93 (95% CI: 0.69–1.24) for women in the third quartile, and 0.88 (95% CI: 0.64–1.16) for women in the fourth quartile.

Compared with women with 1 hour of sun exposure, women with 9 hours of sun exposure had lower mean IMT (multivariable-adjusted mean % difference = −1.8; 95% CI: −4.8 to −1.2). Compared with women in the lowest category of sun exposure, the multivariable adjusted ORs of carotid atherosclerosis were 1.04 (95% CI: 0.83–1.32) for women exposed 3.5 hours, 0.82 (95% CI: 0.51–1.34) for women exposed 7 hours, and 0.54 (95% CI: 0.25–1.18) for women who were exposed 9 hours ( Table 2).

Table 2.

Multivariate-Adjusted Percentage of Differences of Mean Intima-Media Thickness and Odds Ratio for Carotid Atherosclerosis Use in 2,257 Women from the Mexican Teachers' Cohort for Cumulative Sunlight Exposure (Quartiles) and Most Recent Exposure

Cumulative	Quartile 1 (n = 563)	Quartile 2 (n = 550)	Quartile 3 (n = 633)	Quartile 4 (n = 496)	p-trend
Difference, % (95% CI)
Age adjusted	Reference	0.5 (−1.0 to 2.0)	1.0 (−2.0 to 0.7)	–1.6 (−3.0 to −0.01)	0.009
Age and site adjusted	Reference	0.3 (−1.1 to 0.5)	–0.8(−2.3 to 0.6)	–1.0 (−2.5 to 1.8)	0.01
Multivariable^a	Reference	0.4 (−1.0 to 1.8)	–0.8 (−2.2 to 0.7)	–0.8 (−2.3 to 0.8)	0.11
Odds ratio, % (95% CI)
Age adjusted	Reference	0.88 (0.66 to 1.2)	0.88 (0.66 to 1.2)	0.78 (0.58 to 1.0)	0.15
Age and site adjusted	Reference	0.89 (0.66 to 1.2)	0.92 (0.68 to 1.2)	0.85 (0.62 to 1.2)	0.39
Multivariable^a	Reference	0.89 (0.67 to 1.2)	0.93 (0.69 to 1.2)	0.88 (0.64 to 1.2)	0.55

Most recent exposure	1 hour	3.5 hours	7 hours	9 hours	p-trend
Difference, % (95% CI)
Age adjusted	Reference	–0.8 (−6.2 to 0.2)	–2.0 (−4.4 to 0.3)	–2.9(−2.0 to 0.4)	0.01
Age and site adjusted	Reference	–0.8 (−1.9 to 0.4)	–1.6 (−3.7 to 0.6)	–2.0 (−5.0 to 0.3)	0.03
Multivariable^a	Reference	–0.7 (−1.8 to 0.0)	–1.3 (−3.4 to 0.8)	–1.8 (−4.8 to 1.2)	0.07
Odds ratio, % (95% CI)
Age adjusted	Reference	0.99 (0.78 to 1.2)	0.72 (0.45 to 1.2)	0.48 (0.22 to 1.0)	0.05
Age and site adjusted	Reference	1.03 (0.82 to 1.3)	0.79 (0.4 to 1.3)	0.52 (0.24 to 1.1)	0.14
Multivariable^a	Reference	1.04 (0.83 to 1.3)	0.82 (0.51 to 1.3)	0.54 (0.25 to 1.2)	0.23

Values are given as percentage of differences (95% CI) and odds ratio (95% CI) unless otherwise specified.

All models are multivariate analysis adjusted for age (continuous), indigenous (yes or no), site (Monterrey, Mexico City, Yucatan, Chiapas), smoking status (never, past, current), socioeconomic status (tertiles), and physical activity (continuous).

CI, confidence intervals.

For exposure by age categories the magnitude of the effect for adjusted percentage difference seemed higher at increasing ages (−0.4 for 12–24, −0.6 for 25–35, −1.8 for 36–59 years). Likewise, the OR for carotid atherosclerosis decreased with increasing ages (0.94 for 12–24, 0.92 for 25–35, 0.69 for 36–59 years). None of these analyses were statistically significant, but the p-trend for percentage difference for ages 36–59 was significant (p-trend 0.04; Table 3).

Table 3.

Multivariate-Adjusted Percentage Differences of Mean Intima-Media Thickness and Odds Ratio (95% Confidence Intervals) by Tertiles of Sunlight Exposure for Age Categories of Exposure

	Tertile 1	Tertile 2	Tertile 3	p-trend
12–24	n = 697	n = 1127	n = 433
Difference, % (95% CI)	Reference	0.10 (−1.1 to 1.3)	–0.40 (−1.9 to 1.1)	0.62
Odds ratio, (95% CI)	Reference	0.98 (0.77 to 1.2)	0.94 (0.68 to 1.3)	0.68
25–35	n = 881	n = 1008	n = 368
Difference, % (95% CI)	Reference	–0.40 (−1.6 to 0.7)	–0.60 (−2.1 to 1.0)	0.43
Odds ratio, (95% CI)	Reference	0.99 (0.79 to 1.3)	0.92 (0.66 to 1.3)	0.66
36–59^a	n = 1259	n = 773	n = 211
Difference, % (95% CI)	Reference	–0.59(−1.7 to 0.5)	–1.8 (−3.7 to 0.04)	0.04
Odds ratio, (95% CI)	Reference	1.08 (0.86 to 1.4)	0.69 (0.45 to 1.1)	0.32

Values are given as percentage of differences or odds ratio (95% CI) unless otherwise specified.

Multivariate analyses were adjusted for age (continuous), indigenous (yes or no), site (Monterrey, Mexico City, Yucatan, Chiapas), smoking status (never, past, or current), socioeconomic status (tertiles), and physical activity (continuous).

Participants who were 60 or older were excluded because there were <90 women.

For women who denied regular sunscreen use, those in the higher exposure category (9 hours) had lower mean IMT compared with those in the lower category (multivariable-adjusted mean % difference = −2.67; 95% CI: −6.9 to −1.5). The multivariable adjusted ORs for carotid atherosclerosis with women in the lowest category of exposure as reference were 0.97 (95% CI: 0.72–1.30) for women exposed 3.5 hours, 0.72 (95% CI: 0.39–1.35) for women exposed 7 hours, and 0.45 (95% CI: 0.15, 1.35; p-trend = 0.13) for women who were exposed 9 hours (Table 4).

Table 4.

Multivariable-Adjusted Percentage Differences of Mean Intima-Media Thickness and Odds Ratios for Carotid Atherosclerosis (95% Confidence Intervals) for Current Sunlight Exposure by Weekly Hours of Exposure for Women Without Regular Sunscreen Use (n = 1,338)

	1 hour, n = 761	3.5 hours, n = 456	7 hours, n = 84	9 hours, n = 37	p-trend
Percentage differences
Age adjusted	Reference	–1.13 (−2.7 to 0.4)	–0.73(−3.8 to 2.3)	–3.34 (−7.9 to 1.1)	0.09
Multivariable^a	Reference	–1.29 (−2.8 to 0.2)	–1.12 (−4.0 to 1.8)	–2.67 (−6.9 to 1.5)	0.07
Odds ratio
Age adjusted	Reference	0.90 (0.68 to 1.2)	0.69 (0.39 to 1.3)	0.39 (0.14 to 1.2)	0.05
Multivariable^b	Reference	0.97 (0.72 to 1.3)	0.71 (0.38 to 1.3)	0.45 (0.15 to 1.4)	0.13

Values are given as multivariable-adjusted odds ratio (95% CI) unless otherwise specified.

In stratified analyses for BMI, we found that nonobese women in the highest quartile of sun exposure had a lower mean IMT compared with those in the lowest quartile (multivariable-adjusted mean % difference = −0.79; 95% CI: −4.2 to −2.7). For carotid atherosclerosis we did not find a significant association for nonobese women. Analyses for overweight participants did not show effect modification. In obese women the estimate was higher, but not significant. Nevertheless, the p-value for interaction was not significant, suggesting statistical interaction (p for % difference = 0.52; p for OR = 0.12; Supplementary Table S1).

In sensitivity analyses using a stricter definition of carotid atherosclerosis (mean left and right IMT ≥0.8 mm or the presence of plaque) we did not find a statistically significant association between sun exposure and carotid atherosclerosis (Supplementary Table S2).

Finally, in the multivariate-adjusted percentage of differences of mean IMT, for women with most recent exposure (no imputation), those in the higher exposure category (9 hours) had lower mean IMT compared with those in the lower category (multivariable-adjusted mean % difference = −2.8; 95% CI: −6.3 to 0.8, p-trend = 0.04) (Supplementary Table S3).

Discussion

To our knowledge this is the first study in Latin America that evaluates short- and long-term sun exposure and its association with subclinical cardiovascular disease. In general, we observed that cumulative sun exposure was inversely associated with IMT and subclinical carotid atherosclerosis; however, this relationship was not statistically significant. Furthermore, when we analyzed the association between sun exposure (hours/week) and subclinical cardiovascular disease in women without regular sun screen use, we found that women who were exposed to sun >9 hours a week had lower odds of carotid atherosclerosis.

The relation of sun exposure and cardiovascular disease has been analyzed in different countries around the world.^22,33
–35 In this study, sun exposure (>9 hours a week) was associated with lower odds of carotid atherosclerosis. This is consistent with previous results observed in the Swedish population, in which women with increased sun exposure habits had reduced CVD mortality, adjusted for sociodemographic variables, smoking, and comorbidity (hazard ratio = 0.50; 95% CI: 0.40–0.60).

Specifically, for IMT The IMPROVE study³⁶ showed that a major determinant of IMT was latitude with Northern populations having higher IMT than those in the South. This phenomenon has also been reported for coronary heart disease in France and is known as the North–East–South gradient.³⁷ Specific mechanisms causing these differences were not elucidated by the IMPROVE study; nevertheless, confounding by diet and socioeconomic status were discarded, suggesting that the differences found could be explained by environmental effects on cardiovascular risk factors, such as sun exposure.

In addition, when we evaluated sun exposure according to age categories, we observed that in those women aged 36–59 years who had greater sun exposure, IMT was lower than in those of the lowest category of sun exposure (difference = −1.8; 95% CI: −3.7, 0.04; p-trend = 0.04). Moreover, when we analyzed the most recent exposure, we observed that the magnitude of the effect was stronger, but these results were not statistically significant probably because of the small sample size. Recent evidence suggests sun exposure might have a protective role in cardiovascular disease explained by the mobilization of nitric oxide skin stores to systemic circulation, which reduces systolic blood pressure.¹⁰

In agreement with this, observational studies have shown a reduction in blood pressure in participants who were more sun exposed, but these changes were not significant after adjusting for potential confounders.³⁸ Because nitric oxide vasodilation is an immediate effect of sun exposure, cumulative exposure might not reflect the protective role. This is consistent with the higher effect observed in most recent exposure and with the p-trend on exposure from 36 to 59 years, which is the age category closest to the average age of participants at the time of IMT measurement. Other studies have also shown a protective effect only from recent exposure.³⁹

There is rising evidence that sun exposure might play a protective role in mortality and cardiovascular outcomes.^23,34 Historically, vitamin D synthesis has been the proposed mechanism for safe sun exposure, by modifying calcium influx into endothelial cells as well as effects on vascular tone.⁴⁰ The role of vitamin D as a negative regulator of the renin–angiotensin–aldosterone system has also been proposed.⁴¹ Because vitamin D deficiency has also been linked to adverse cardiovascular outcomes and cancer,^42,43,,44 several clinical trials with supplementation have been conducted to determine if improvement in cancer and cardiovascular outcomes occurred.

Most trials have shown null results; one evaluated vitamin D supplementation and IMT⁴⁵ and a large randomized double-blind trial showed no improvement in cardiovascular outcomes or cancer after supplementation with high doses of vitamin D (2000 UI).⁴⁶ These results suggest that vitamin D might be related to cardiovascular health but not through a causal relationship. Vitamin D has been suggested as a marker of sun exposure.⁴⁴ Despite the fact vitamin D has a biological half-life of several weeks,⁶ it would be plausible that our longer term sunlight exposure would have a larger effect on vitamin D levels, and thus on cardiovascular risk.

In addition, for specific cardiovascular outcomes like stroke, it has been suggested that sun exposure modifies autonomic and endothelial function, increases levels of cholesterol and fibrinogen, increases blood viscosity, and hormonal variation, but the specific mechanisms through which sun exposure causes these modifications remain unclear.⁴⁷

Our analyses have some strengths, including a population-based design and the assessment of the exposure through an extensive questionnaire. Another strength is the high-quality assessment of IMT, which was conducted by standardized neurologists and with a high reproducibility technique. However, the possibility of random error cannot be ruled out. Evaluating short- and long-term sun exposure is also a strength, as well as assessing this exposure in sites with different latitudes and therefore different sun exposures.

It is important to mention some methodological limitations that might affect the interpretation of our results. First, because it is a cross-sectional study, it is not possible to address the causal sequence; however, it is unlikely that carotid atherosclerosis of which the participants were not aware of could have changed sun exposure reports. Furthermore, although we adjusted for potential confounding factors, there are other confounder factors that we have not considered and limit the direct effect of sun exposure on IMT, so the presence of residual confounding is possible. However, we were able to control confounding for common causes of sun exposure and atherosclerosis. A small number of participants and the limited variability of the exposure might limit the power of our study, but we believe this variability is representative of Mexican sun exposure habits.

There are few validated sun exposure questionnaires, and some studies have tried to assess sun exposure with estimations of UV radiation in geographical areas. However, questionnaires estimate sun exposure more effectively because they reflect actual behavior toward sun exposure. Ambient UV radiation and latitude provide rough estimates of UV exposure because individual behaviors regarding sun exposure vary widely within individuals and within life periods.⁴⁸ Even if recall bias cannot be ruled out, asking for previous exposures allowed us to evaluate the differences between cumulative and most recent exposure and we did not assume that sun exposure habits do not change over time. Another potential limitation is that our study lacks any change with sun exposure and vitamin D levels; nevertheless, previous studies have suggested that changes on vitamin D concentrations are primarily regulated by solar radiation.

In addition, it was not possible to measure the body area directly exposed to the sun, so exposure misclassification could exist as a potential source of bias. Because our cohort study includes only women, our data cannot be generalized to adult Mexican men. Finally, the effects observed could be owing to other factors like increase in physical exercise and dietary factors and may not be because of sun exposure directly; also, sun exposure may be related to many other factors that are unfortunately not taken into account. Hence, further large studies need to be performed to validate the results.

Conclusions

Public health recommendations regarding sun exposure primarily focus on its avoidance and regular sunscreen use because of long-standing concerns regarding skin cancer. These recommendations tend to ignore that sun exposure is the main source of vitamin D and that oral supplements fail to substitute actual sun exposure.^45,46,49 Rising evidence, including our study, suggest that historical recommendations of sun avoidance should be questioned and further investigated in view of the potential health benefits of increasing sun exposure.

Our findings suggest that public health messages should consider a positive role for sun while still emphasizing the negative impacts of excessive exposure. Future studies regarding the effects of differing long-term and acute sun exposure on various risk factors conceptualized in terms of both disease and reactivity are needed to explore these relationships.

Footnotes

Acknowledgments

The authors thank all study participants for their time and continued support of the Mexican Teachers' Cohort (ESMaestras). The authors thank the leadership at the office for Regulation at Carrera Magisterial (now Unidad del Sistema para la Carrera de las Maestras y Maestros) in Mexico's Ministry of Education as well as state coordinators in Chiapas, Yucatán, and Nuevo León for their support in contacting Mexican Teachers' Cohort participants and assisting with operations during the clinical visits. The authors acknowledge the commitment to the study by ISSSTE's Prevention and Health Protection area within the Medical Sub-Directorate by providing technical and logistical support in data collection and hosting clinical visits in their facilities in Chiapas and Yucatán. For data collection in Nuevo León, the authors thank TecSalud's School of Medicine and Medical Sciences and ISSSTE León for limited financial support and hosting our research team for clinical data collection.

Authors' Contributions

The authors' contributions were as follows: M.L., R.L.-R., A.C.-K., and E.D.-G., designed research; M.A., P.M.-A., A.C.-V., and M.H.F.-T., conducted research; M.A., A.C.-V., B.L.R., and C.C.-B., analyzed data; M.A., P.M.-A., A.C.-V., and E.D.-G., performed statistical analysis; M.A., and P.M.-A., wrote article; all authors reviewed the article, and all authors had primary responsibility for final content.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This work was supported by CONACyT (Grant No. SALUD 161786 and FOINS 214145), Bernard Lown Scholars in Cardiovascular Health Program at the Harvard T.H. Chan School of Public Health, and a no restricted grant from AstraZeneca (Grant No. ISSNPCV0022).

Supplementary Material

Supplementary Table S1

Supplementary Table S2

Supplementary Table S3

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