The Mean Platelet Volume Is Positively Correlated with Serum Thyrotropin Concentrations in a Population of Healthy Subjects and Subjects with Unsuspected Subclinical Hypothyroidism

Abstract

Background:

A possible prothrombotic effect of elevated thyrotropin (TSH) has been suggested. The mean platelet volume (MPV), which is used to measure the platelet size, can reflect platelet activity. Although limited and inconsistent data regarding the effects of thyroid function on the MPV are available from small-scale case-control studies, no study has been based on a general population, particularly in euthyroid states. The objective of the present study was to determine whether there is an association between the MPV and serum TSH concentrations in an apparently healthy Korean population without overt thyroid disease, but including subjects with unsuspected subclinical hypothyroidism (SCH).

Methods:

We retrospectively studied 6893 asymptomatic Korean adults who were 20 years of age or older and who underwent voluntary regular health check-ups at the Health Promotion Center of Chosun University Hospital. The subjects who met the inclusion and exclusion criteria were subdivided into four groups, such as tertile groups for the TSH reference range and an SCH (TSH ≥4 μIU/mL with a normal free T4 concentration) group according to the TSH level. We compared the mean values of the MPVs among the groups. Multivariate logistic regression analyses were used to identify associations between the highest tertile of the MPV and the TSH subgroups.

Results:

The mean level of the MPV in all study subjects was 8.12±0.75 femtoliters (fL), and the mean value of the MPV was significantly different in each group. The mean MPV in SCH was significantly higher compared with those of the first tertile (T1) and second tertile (T2). Moreover, the mean MPV increased statistical significantly by increasing tertiles of the TSH concentration and was highest in SCH (T1, 8.08±0.81 fL; T2, 8.09±0.62 fL; T3, 8.13±0.77 fL; SCH, 8.21±0.81 fL; p for trend=0.012). After adjusting for risk factors associated with increasing MPVs and platelet counts, SCH was independently associated with the highest tertile of the MPV (all subjects, odds radio (OR) 1.58 [95% confidence interval (CI) 1.19–2.09]; men, OR 1.70 [CI 1.10–2.64]; women, OR 1.55 [CI 1.06–2.26]).

Conclusions:

The MPV was positively correlated with the TSH level. SCH is an independently associated factor with the highest tertile of MPV in a general Korean population. We propose that the MPV may contribute to the prothrombotic condition that is associated with SCH and perhaps even in putative euthyroid states where the TSH level is the higher part of the normal range.

Introduction

T hyroid hormone is an essential regulator in the development of atherosclerotic cardiovascular disease (CVD) by direct effects and contributing to risk factors (1). Despite some conflicting results, subclinical hypothyroidism (SCH), similar to overt hypothyroidism, accelerates atherogenesis (2). Previous studies have reported that SCH was an independent risk factor of CVD (3 –6). Even the upper range of the thyrotropin (TSH) reference range may accelerate the development of artherosclerosis in euthyroid states (7). However, the underlying mechanism has not yet been determined. Recently, a hypercoagulable state and prothrombotic characteristics have been suggested as contributing conditions (8).

Platelets play an important role in atherothrombosis. Larger platelets are likely to be more reactive, contain more granules, and produce greater amounts of vasoactive and prothrombotic factors (9). The mean platelet volume (MPV), which is used to measure platelet size, can reflect the platelet activity (10). Several studies reported that an elevated MPV was associated with atherosclerotic lesions and CVD (11 –13). Moreover, higher MPVs were associated with diabetes, hypertension, dyslipidemia, smoking, and obesity, which are CVD risk factors (14 –16).

Currently, limited and conflicting data regarding the relationship between thyroid function and MPV have been reported in small-scale case-control studies (17 –22). To our knowledge, no study has been based on a general population, particularly in those who were thought to be healthy and euthyroid.

The objective of the present study was to determine whether there was an association between the MPV and the TSH level in an apparently healthy Korean population who were thought to be healthy and euthyroid. We also identified an independent range of the TSH level that was associated with the highest tertile of MPV in euthyroid states and SCH.

Materials and Methods

Study populations

We retrospectively studied 6893 asymptomatic Korean adults who were 20 years of age or older and who underwent voluntary regular health check-ups at the Health Promotion Center of Chosun University Hospital (Gwangju, Republic of Korea) from January 2009 to September 2011. We included individuals with free thyroxine (FT4) levels within the reference range and TSH levels within the reference range or above the upper limit of the reference range while not taking any thyroid medication and without a history of thyroid disease. Individuals with overt thyroid disease or suppressed TSH concentrations were excluded. The following reference ranges for the thyroid panel were used according to the standards of our hospital's biochemistry laboratory: 0.25–4 μIU/mL TSH and 0.7–1.8 ng/dL FT4. Individuals who had been previously diagnosed with diabetes, hypertension, or dyslipidemia and those had been treated with hypoglycemic agents, antihypertensive agents, and lipid-lowering agents were excluded. Other exclusion criteria included coronary artery disease (CAD), stroke, acute infection, pregnancy, malignancy, liver cirrhosis, and impaired renal function, as well as those individuals with serum liver enzyme activities higher than twice the upper normal limit, those with white blood cell (WBC) counts of <3.0 or >10.0×10⁹ cells/L, those with platelet counts of <150 or >400×10⁹ cells/L, those with a hemoglobin level of <12.0 g/dL for women or <13.0 g/dL for men, and those with missing data. After these exclusions, 2997 individuals (aged 20–81 years, mean age=46.17±10.56; men/women 1566/1431) were included in this study.

This study was approved by the Institutional Review Board of Chosun University Hospital.

Clinical examination and laboratory methods

Data were collected through questionnaires (medical history), a physical examination (height, weight, waist circumference [WC], and blood pressure), and blood collection. Smoking status was divided into current smoker, ex-smoker, and nonsmoker. Height and weight were measured while each subject was wearing light clothing without shoes. Body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. WC was measured midway between the costal margin and the iliac crest at the end of a normal expiration. Blood pressure was measured with a mercury sphygmomanometer on the right arm in the sitting position after a 5-minute rest. After an overnight (>8 hours) fast, venous blood samples were obtained and collected in K2-ethylenediaminetetraacetic acid (EDTA) and serum separator blood-drawing tubes. TSH and FT4 levels were measured using a radioimmunoassay. The MPV value and platelet count were analyzed using an Advia 2120 Hematology Analyzer (Siemens Healthcare Diagnostic GmbH). The fasting plasma glucose (FPG) level was measured using the hexokinase enzymatic method. Levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides were measured with an ADVIA 1650. HbA1c level was measured using ion-exchange high-performance liquid chromatography (Variant II^™; Bio-Rad).

Classification by thyroid status

For data analysis, subjects were subdivided into four groups, following the tertile groups based on the TSH reference range and an SCH group according to the TSH level. The division by tertile was as follows: first tertile (T1), 0.25–0.46 μIU/mL; second tertile (T2), >0.46–2.31 μIU/mL; and third tertile (T3), >2.31–4 μIU/mL. Within the reference range, T1 represents the lowest TSH level, while T3 represents the highest TSH level. SCH was defined as a TSH ≥4 μIU/mL with a normal free T4 concentration.

Statistical analysis

The comparisons among groups were performed using a one-way ANOVA for continuous variables, and a chi-squared test was used for noncontinuous variables. A post-hoc analysis using Scheffe's method was used to compare differences between the groups. MPVs were subdivided into tertiles according to the distribution of the MPV, and the highest tertile of the MPV was determined for all subjects and for men and women separately. Multivariate logistic regression analyses were used to identify associations between the highest tertile of the MPV and the TSH subgroups by evaluating the odds ratio after adjusting for clinical and biochemical variables that were associated with an increased MPV. Statistical analyses were performed using SPSS software (version 18.0), and a p-value of <0.05 was considered statistically significant.

Results

The prevalence of SCH was 10% (301/2997) in all subjects, 7.3% (114/1566) in men, and 13.1% (187/1431) in women (data not shown). The clinical and biochemical characteristics of the subjects are presented in Table 1. The mean age of the subjects was 46.17±10.56 years. Men were more likely to have higher BMI, WC, systolic and diastolic blood pressure, FPG, HbA1c, lipid profile, and smoking rate than women.

Table 1.

Clinical and Biochemical Characteristics of All Subjects

	Total	Men	Women	p-value
n	2997	1566 (52.3%)	1431 (47.7%)
Age group				0.201
20–29 years	117 (3.9%)	55 (3.5%)	62 (4.3%)
30–39 years	725 (24.2%)	366 (23.4%)	359 (25.1%)
40–49 years	1094 (36.5%)	596 (38.1%)	498 (34.8%)
50–59 years	706 (23.6%)	377 (24.1%)	329 (23.1%)
60–69 years	294 (9.8%)	140 (8.9%)	154 (10.8%)
≥70 years	61 (2.0%)	32 (2.0%)	29 (2.0%)
Age (years)	46.17±10.56	46.17±10.30	46.16±10.85	0.990
BMI (kg/m²)	23.61±3.02	24.28±2.80	22.88±3.08	0.000
WC (cm)	82.47±8.39	85.64±7.13	78.99±8.29	0.000
SBP (mmHg)	121.34±13.43	123.74±12.61	118.72±13.80	0.000
DBP (mmHg)	73.47±10.41	75.27±10.37	71.50±10.08	0.000
Plt (count/mm³)	261.68±50.73	257.97±48.35	265.73±52.93	0.000
MPV (fL)	8.12±0.75	8.10±0.75	8.14±0.74	0.047
TSH (μIU/mL)	2.29±1.43	2.08±1.29	2.51±1.54	0.000
Free T4 (ng/dL)	1.28±0.27	1.33±0.27	1.22±0.26	0.000
FPG (mg/dL)	88.47±16.13	90.75±17.86	85.97±13.57	0.000
HbA1c (%)	5.65±0.59	5.69±0.64	5.62±0.53	0.001
TC (mg/dL)	189.61±32.30	191.60±31.29	187.43±33.29	0.000
TG (mg/dL)	123.76±85.85	144.70±91.21	100.83±73.01	0.000
LDLc (mg/dL)	119.13±29.96	122.20±28.30	115.76±30.64	0.000
HDLc (mg/dL)	53.49±12.42	50.41±11.25	56.86±12.77	0.000
Smoking				0.000
Nonsmoker	1923 (64.2%)	539 (34.4%)	1384 (96.7%)
Current smoker	798 (26.6%)	757 (48.3%)	41 (2.9%)
Ex-smoker	276 (9.2%)	270 (17.2%)	6 (0.4%)

The data are mean±SD.

BMI, body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDLc, high-density lipoprotein cholesterol; LDLc, low-density lipoprotein cholesterol; MPV, mean platelet volume; Plt, platelet count; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride; TSH, thyrotropin; WC, waist circumference.

The mean level of TSH was 2.29±1.43 μIU/mL, and the mean level of FT4 was 1.28±0.27 ng/dL. The mean level of MPV was 8.12±0.75 femtoliters (fL). The average MPV was higher in the women (8.14±0.74 fL) than in the men (8.10±0.75 fL).

Comparison of clinical and biochemical characteristics among TSH subgroup

The characteristics of the subjects according to the TSH tertiles and one SCH subgroup are shown in Table 2. As expected, free T4 levels were decreased significantly across the TSH tertiles and were the lowest in the SCH group. Age distribution and smoking rate were significantly different among TSH subgroups. No significant differences were found for the mean values of age, BMI, WC, systolic and diastolic blood pressure, FPG, HbA1c, lipid profile, and platelet count among each TSH tertile and the SCH group.

Table 2.

Clinical and Biochemical Characteristics Stratified by Tertiles of the Thyrotropin Reference Range and Subclinical Hypothyroidism

	T1	T2	T3	SCH	p-Value	p for trend
n	909	891	896	301
Sex					0.000
Men	558 (61.4%)	484 (54.3%)	410 (45.8%)	114 (37.9%)
Women	351 (35.6%)	407 (45.7%)	486 (54.2%)	187 (62.1%)
Age group					0.017
20–29 years	28 (3.1%)	26 (2.9%)	40 (4.5%)	23 (7.6%)
30–39 years	210 (23.1%)	224 (25.1%)	218 (24.3%)	73 (24.3%)
40–49 years	359 (39.5%)	333 (37.4%)	309 (34.5%)	93 (30.9%)
50–59 years	199 (21.9%)	207 (23.2%)	229 (25.6%)	71 (23.6%)
60–69 years	97 (10.7%)	84 (9.4%)	78 (8.7%)	35 (11.6%)
≥70 years	16 (1.8%)	17 (1.9%)	22 (2.5%)	6 (2.0%)
Age (years)	46.42±10.28	46.29±10.27	46.03±10.85	45.46±11.40	0.544	0.171
BMI (kg/m²)	23.71±2.96	23.60±2.94	23.57±3.05	23.47±3.32	0.617	0.192
WC (cm)	82.70±8.34	82.48±8.25	82.32±8.45	82.14±8.76	0.706	0.239
SBP (mmHg)	121.68±13.59	121.05±13.19	121.14±13.37	121.81±13.82	0.664	0.771
DBP (mmHg)	73.77±10.51	73.15±10.31	73.31±10.49	74.00±10.09	0.464	0.869
Plt (count/mm³)	260.86±49.03	261.61±50.15	262.89±52.47	260.72±52.32	0.836	0.645
MPV (fL)^*	8.08±0.81^a	8.09±0.62^a	8.13±0.77^a,b	8.21±0.81^b	0.047	0.012
Free T4 (ng/dL)^*	1.30±0.27^a	1.29±0.27^b	1.27±0.27^b	1.20±0.29^b	0.000	0.000
FPG (mg/dL)	89.30±16.70	88.24±15.01	88.29±16.71	87.15±15.73	0.197	0.049
HbA1c (%)	5.67±0.58	5.64±0.55	5.66±0.65	5.64±0.55	0.744	0.564
TC (mg/dL)	189.80±32.65	190.54±32.43	189.45±31.10	186.75±34.26	0.370	0.241
TG (mg/dL)	123.57±84.32	126.12±88.47	121.19±81.95	124.98±93.74	0.674	0.763
LDLc (mg/dL)	119.14±29.84	119.73±30.09	119.43±29.69	116.40±30.77	0.401	0.395
HDLc (mg/dL)	53.28±12.34	53.42±12.55	53.59±12.30	54.04±12.70	0.816	0.564
Smoking					0.000
Nonsmoker	506 (55.7%)	564 (63.3%)	622 (69.4%)	231 (76.7%)
Current smoker	320 (35.2%)	249 (27.9%)	185 (20.6%)	44 (14.6%)
Ex-smoker	83 (9.1%)	78 (8.8%)	89 (9.9%)	26 (8.6%)

The data are the means±SD.

The presence of the same letter indicates a nonsignificant difference between those groups based on Scheffe's multiple-comparison test.

T1, first tertile (TSH 0.25–0.46 μIU/mL); T2, second tertile (TSH >0.46–2.31 μIU/mL); T3, third tertile (TSH >2.31–4.00 μIU/mL); SCH, subclinical hypothyroidism (TSH >4.00 μIU/mL).

Comparison of mean values of MPV among TSH subgroup

The mean values of MPV were significantly different in each of the TSH subgroups. The mean value of MPV in the SCH group was significantly higher compared with the T1 and T2 groups. Moreover, the mean value of MPV increased significantly by increasing tertiles of the TSH concentration and was highest in SCH (T1, 8.08±0.81 fL; T2, 8.09±0.62 fL; T3, 8.13±0.77 fL; SCH, 8.21±0.81 fL; p for trend=0.012).

Relationship between MPV and TSH

Table 3 shows the multivariable-adjusted relationship between the highest tertiles of the MPV and the TSH range. The highest tertile of the MPV was ≥8.3 fL for all subjects, as well as for men and women separately. After adjustments for age and sex, SCH was independently associated with the highest MPV tertile (odds radio (OR) 1.54 [95% confidence interval (CI) 1.17–2.01]) in all subjects. These independent associations were demonstrated in both men (OR 1.52 [CI 1.02–2.30]) and women (OR 1.56 [CI 1.09–2.25]) after having adjusted for age. The independent association between the highest MPV tertile and SCH remained significant in all subjects (OR 1.55 [CI 1.82–2.02]) and both sexes (men, OR 1.55 [CI 1.02–2.35]; women, OR 1.57 [CI 1.09–2.27]) after having adjusted for BMI, WC, systolic and diastolic blood pressure, FPG, and HbA1c, in addition to the previously described factors. These significant associations remained after adjusting for the previous factors as well as for the lipid profile, smoking status, and platelet counts (all subjects, OR 1.58 [CI 1.19–2.09]; men, OR 1.70 [CI 1.10–2.64]; women, OR 1.55 [CI 1.06–2.26]).

Table 3.

Odds Ratios and 95% Confidence Intervals for the Highest Tertile of the Mean Platelet Volume, According to the Tertiles of the Thyrotropin Reference Range and Subclinical Hypothyroidism

	T1	T2	T3	SCH
All subjects
Model 1a	1.00	1.12 [0.92–1.36]	1.10 [0.90–1.34]	1.54 [1.17–2.01]^*
Model 2a	1.00	1.12 [0.92–1.36]	1.11 [0.92–1.35]	1.55 [1.18–2.02]^*
Model 3a	1.00	1.14 [0.93–1.39]	1.12 [0.92–1.37]	1.58 [1.19–2.09]^*
Men
Model 1	1.00	1.06 [0.82–1.37]	1.07 [0.81–1.40]	1.52 [1.01–2.30]^*
Model 2	1.00	1.08 [0.84–1.41]	1.09 [0.83–1.44]	1.55 [1.02–2.35]^*
Model 3	1.00	1.11 [0.85–1.46]	1.08 [0.81–1.43]	1.70 [1.10–2.64]^*
Women
Model 1	1.00	1.21 [0.90–1.63]	1.14 [0.86–1.52]	1.56 [1.09–2.25]^*
Model 2	1.00	1.21 [0.90–1.63]	1.15 [0.86–1.53]	1.57 [1.09–2.27]^*
Model 3	1.00	1.20 [0.88–1.63]	1.16 [0.86–1.56]	1.55 [1.06–2.26]^*

Data are odds ratios [95% confidence intervals]. The highest tertile of MPV was ≥8.3 fL for all subjects, ≥8.3 fL for men, and ≥8.3 fL for women. Models were adjusted as follows: 1, for age; 1a, for age and sex; 2, for age, FPG, HbA1c, SBP, DBP, BMI, and WC; 2a, for the factors in Model 2 as well as for sex; 3, for the factors in Model 2 as well as TG, HDLc, smoking status, and Plt; 3a, for the factors in Model 3 as well as for sex.

p<0.05.

Discussion

The results of the present study demonstrated a significant positive association between the TSH level and MPV. In particular, SCH was independently associated with the highest MPV tertile after adjustments for risk factors that are associated with an increased MPV. To our knowledge, this is the first general population-based study that investigated the association between the TSH level and MPV. It shows that the influence of thyroid function on MPV due to SCH even extends into the euthyroid states.

Thyroid hormone has antiatherosclerotic effects (1). Overt hypothyroidism has been known to be related to accelerated atherogenesis through a modulation of atherosclerotic risk factors and direct effects that lead to the development of CVD (23). SCH is defined by serum TSH levels that are above the upper limit of the reference ranges but normal FT4 and free triiodothyronine (FT3) concentrations (24). Although controversy still remains, it has been suggested that SCH has a strong impact on the risk of atherosclerotic lesions and cardiovascular events (2). In a Rotterdam study (3), SCH had an association with myocardial infarction (MI) and aortic calcification. The Busselton Health study (4) reported that SCH is an independent risk factor for CAD. Several meta-analyses found an association between SCH and CAD (5,6). In addition, even levels in the upper range of the TSH reference range may accelerate the development of artherosclerosis and produce changes in cardiovascular performance (7). Serum TSH concentrations are strongly associated with components of metabolic syndrome, which cluster with cardiovascular risk factors, even in euthyroid states (25). These results suggest a possible prothrombotic effect of elevated TSH. The mechanism by which elevated TSH, even within the reference range, may lead to artherosclerosis and its complications is not clear. Recently, several parameters that are considered risk factors for artherosclerosis, including homocysteine, C-reactive protein, endothelial dysfunction, and arterial stiffness, have been proposed to play a role in SCH (26). However, there is insufficient evidence to explain all of the causal relationships, although some studies have suggested a hypercoagulable state and prothrombotic characteristics in overt hypothyroidism (8).

Platelets play a crucial role in the pathophysiology of atherosclerotic diseases that are related to thrombosis, inflammation, and angiogenesis. Large platelets are more active hemostatically and enzymatically, and they contain more prothrombotic molecules, such as platelet factor 4, serotonin, and platelet-derived growth factor (9). Platelet size can be measured by the MPV. An increased MPV may lead to a prothrombotic condition with increased thromboxane A2 and B2 and adhesion molecules, such as P-selectin and glycoprotein IIb/IIIa expression, as well as β-thromboglobulin release. Moreover, the response to ADP was greater aggregability and decreased inhibition of aggregation by prostacyclin. A decrease in prostacyclin leads to vasoconstriction (10). Therefore, an elevated MPV may be considered a potential marker that reflects adverse atherosclerotic events. A previous study reported that an elevated MPV was a risk factor and a prognostic indicator of prothrombotic disease, such as CVD (11). It was noted that a high MPV was an independent risk factor for CAD and MI (12). In addition, an increased MPV was positively correlated with arterial stiffness (13). Moreover, an increased MPV was associated with diabetes, obesity, hypertension, smoking, and dyslipidemia, which are CVD risk factors (14 –16).

A few studies have evaluated a possible association between the MPV and thyroid status, with conflicting results. Van Doormaal et al. (17) found small-sized platelets in overt hypothyroidism, whereas Ford et al. (18) did not show small-sized platelets in overt hypothyroidism. Coban et al. (19), Erikci et al. (20), and Yilamz et al. (21) reported an increased MPV in the SCH group compared with the euthyroid states. In premenopausal women with a low cardiac risk, overt hypothyroidism and SCH did not influence MPV (22). Previous studies showing the contribution of thyroid status to MPV was noted in small-scale case-control studies. Unlike previous studies, we evaluated the relationship between MPV and thyroid status in an apparently healthy general population, even extended into the euthyroid status. MPV can differ with regard to individual characteristics, including genetics and different populations and regions. These discrepancies may originate from the heterogeneity of the study subjects with regard to individual characteristics, age, sex, and race/ethnicity.

Studies evaluating an elevated MPV in SCH have reported a wide range of MPVs (6–12.4 fL) (21). Moreover, the cutoff value of MPVs that contribute to CVD has not yet been determined. Muscari et al. suggested 8.4 fL as a cutoff value for predicting cardiovascular events (27). In our study subjects, the lower limit of the highest MPV tertile was 8.3 fL in all subjects, as well as in men and women separately. We found that the mean value of MPV increased significantly with an increasing TSH tertile in euthyroid states and was highest in the SCH group. SCH was significantly associated with the highest MPV tertile. The relationship between MPV and platelet count is unclear (28). It may be argued that an elevated MPV is secondary to other factors that are affected with the MPV. However, these results remained after adjustments for all conditions associated with MPV and platelet counts in all subjects as well as in the men and the women. It seems reasonable to suggest that MPV plays a role in the thrombotic process and that elevated TSH levels are not only a causal factor.

Other than platelet function, various changes in the coagulation-fibrinolytic system have been described with regard to the thrombotic characteristics of the thyroid hormone alterations. Most studies found no significant association between an increased platelet count and the incidence of atherosclerotic events (28). Increased fibrinogen, factor VII activity, and plasminogen activator inhibitor-1 levels and decreased antithrombin III concentration, factor VIII, and von-Willebrand factor activities are indicated in SCH (8). However, the role of the coagulation-fibrinolytic system in the pathophysiology of artherosclerosis and arterial thrombosis is still debatable, and the available evidence for this important role is lacking and requires larger-scale studies.

It had been suggested that MPV increases on storage in EDTA and that the results become increasingly unreliable after 4 hours (29). Although the time of the exposure to EDTA could not be standardized because our study was conducted retrospectively, the blood analyses were usually processed within 2 hours of the blood collection in our hospital. Thus, the possibility of a storage-related error is minimal. The increasing MPV over time was reported to be <0.5 fL within 2 hours to analysis (11).

The limitations of this study include the small sample size and the fact that the measurements were performed at a certain time as a cross-sectional design; thus, a causal relationship could not be clearly determined. The lack of the FT3 concentration is also a limitation of this study, as is the single measurement of the TSH level. The biologic variability of TSH might result in assignment of some subjects to another thyroid status. We could not include thyroid autoantibodies in our assessment. Other limitations were that the risk factors for CVD and a specific outcome could not be assessed. Thus, we cannot provide insights into whether elevated MPVs actually cause atherosclerotic events. A prospective study that evaluates the relationship between the MPV, thyroid function, and cardiovascular phenotype is needed. In addition, data on the use of antiplatelet agents were not available, but we excluded subjects who had a known history of CAD and stroke. Finally, our results may not be generalizable to all Koreans, because the study participants were volunteers who attended regular health check-ups. Despite these limitations, this study is meaningful, because it is the most current data available that investigate the possibility of an association between MPV and thyroid function in a general population in both SCH and euthyroid states.

In conclusion, MPV was positively correlated with the TSH level, and SCH is an independently associated factor with the highest MPV tertile in a Korean general population. We propose that MPV may contribute to the prothrombotic condition that is associated with SCH and even with the higher TSH levels in euthyroid states. Therefore, more attention should be focused on platelet function for effective management and the prediction of thrombotic events in SCH. A prospective study is needed.

Footnotes

Acknowledgment

This study was supported by research funds from Chosun University, 2010.

Disclosure Statement

The authors declare that no competing financial interests exist.

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