Cold hypersensitivity in the lower extremities: an underappreciated symptom in patients with varicose veins

Introduction

Varicose veins are characterised by the emergence of elongated, tortuous or contorted veins in the lower extremities. This condition is significantly attributable to compromised functionality of valves within deep or superficial veins, perforator veins, venous tributaries and occasionally venous obstructions. These factors collectively increase venous pressure and impede blood flow. The prevalence of varicose veins in adults ranges from 2% to 30%, with a higher prevalence among women.1 The symptoms frequently linked with varicose veins include sensations of heaviness, aching, swelling, throbbing, itching, restlessness in the legs, oedema (fluid retention), muscle cramps, formation of leg ulcers and a sensation of tightness in the affected region.2

Coldness in the extremities refers to a subjective and uncomfortable sensation in the hands, feet or other peripheral body areas, even when the ambient temperature is within the normal range. Studies indicate that this sensation is correlated with various chronic conditions including arthritis, gastritis, gastroduodenal ulcers, reflux oesophagitis and rhinitis,3 implying that these conditions may be crucial in initiating or intensifying the perception of coldness in the hands, feet or other peripheral extremities. However, these diseases do not encompass other leg-related symptoms such as heaviness, cramping pain, sensations of tightness or swelling.

During the clinical evaluation of patients presenting with varicose veins, the concurrent occurrence of frequent complaints related to cold legs usually remains unrecognised. Additionally, cold hypersensitivity is frequently overlooked, particularly during clinical encounters. Notably, cold hypersensitivity is more prevalent in the East Asian population, with a significantly higher occurrence rate observed in women.3 4 The connection between this symptom and varicose veins is partially acknowledged or emphasised in the literature or during routine clinical assessments.5–7 Therefore, we aimed to explore the relationship between venous leg symptoms—specifically the sensation of heaviness and varying degrees of cold sensitivity—in individuals diagnosed with varicose veins.

Methods

The data were obtained from the Taiwan Biobank, the largest genetic and population-based database in Taiwan. Volunteers aged 30–70 years without a history of cancer who were strictly Taiwanese were included. All volunteers signed an informed consent form before enrolment, and physical examinations, bioinformatics analyses and questionnaires were administered during recruitment. The data were collected between January 2008 and December 2020.

Varicose veins were defined in the questionnaire by the question: “Can you see distorted blood vessels on your four limbs (varicose veins)?” The answer choices were none, mild, moderate, severe or extreme. We excluded those with mild varicose veins and classified those who answered ‘none’ as controls, while those with moderate, severe and extreme varicose veins were classified as cases. For cold hypersensitivity, the option “I feel cold, cold hypersensitivity in hands and feet, or need to put on more clothes” was presented. Cold hypersensitivity was divided into three groups: (1) no cold hypersensitivity; (2) mild cold hypersensitivity; and (3) those with moderate, severe or extreme were classified as severe cold hypersensitivity. To determine if patients had heavy legs, the following question was asked: “Do you feel heavy in your body or lower body?” There were two groups of heavy legs: (1) non-heavy legs, including those answering none or mild; and (2) heavy legs for those with moderate, severe or extreme heaviness. Both evaluations of cold hypersensitivity and heavy legs were based on self-reported symptoms assessed by patients. Other covariates in the logistic regression model included sex (women/men), vegetarian diet (yes/no), age, cigarette smoking (yes/no), alcohol intake (yes/no), exercise (yes/no), body mass index (BMI) (normal weight/underweight/overweight obese), education level (elementary and below/junior and senior school/university and above), job type (non-prolonged standing/prolonged standing), hypertension (yes/no) and diabetes (yes/no).

SAS version 9.4 (SAS Institute, Cary, North Carolina, USA) was used to analyse the associations among individuals with cold hypersensitivity, heavy legs and varicose veins. Odds ratios (OR) with 95% confidence intervals (CI) were determined using logistic regression. Analysis of variance was used to examine the differences between cold hypersensitivity and continuous variables. The results are shown as mean±SE. The χ² test was used to examine the differences between the cold hypersensitivity status and categorical variables. The results are presented as numbers and percentages, and the significance level was set at p<0.05.

Results

After excluding participants with incomplete and missing values and those with mild varicose veins, 8782 participants were included in the analysis. The basic characteristics of the participants according to cold hypersensitivity are shown in table 1. Among those with no, moderate and severe cold sensitivity, 5.77%, 9.38% and 14.13% had varicose veins, respectively, while 4.74%, 7.36% and 14.13% had heavy legs (p<0.0001). In those with no cold hypersensitivity (n=5888), 340 (5.77%) had varicose veins while 5548 (94.23%) did not. Similarly, significant differences were observed between cold hypersensitivity status and sex, age, cigarette smoking, alcohol intake, exercise, BMI, education level, hypertension and diabetes (p<0.0001). In addition, job type was associated with cold sensitivity (p=0.0384).

Logistic regression was used to analyse the associations between cold hypersensitivity, heavy legs and varicose veins (table 2). Moderate and severe cold hypersensitivities were associated with a higher risk of varicose veins, with an OR of 1.490 (95% CI 1.205 to 1.842) and 1.894 (95% CI 1.546 to 2.320), respectively, than no cold hypersensitivity. Similarly, heavy legs were associated with varicose veins (OR 4.239; 95% CI 3.381 to 5.315). Men had a lower risk of varicose veins than women (OR 0.241; p<0.0001). Age and job type were associated with an increased risk of varicose veins, with ORs of 1.013 (95% CI 1.004 to 1.023) and 1.452 (95% CI 1.219 to 1.730), respectively. Furthermore, the association between cold hypersensitivity and heavy legs was significant (p=0.0009).

Table 3 shows the association between heavy legs and varicose veins stratified based on cold hypersensitivity. In the absence of cold hypersensitivity, the OR for heavy legs and varicose veins was 7.141 (95% CI 5.191 to 9.823) compared with that of non-heavy legs. Furthermore, the ORs were 1.905 (95% CI 1.072 to 3.385) for moderate cold hypersensitivity and 3.175 (95% CI 2.140 to 1.710) for severe cold hypersensitivity.

Table 4 shows the association between cold hypersensitivity and varicose veins stratified according to heavy legs. Compared with no cold hypersensitivity in non-heavy legs, moderate and severe cold hypersensitivities were associated with varicose veins, with ORs of 1.802 (95% CI 1.435 to 2.264) and 2.199 (95% CI 1.753 to 2.758), respectively. In those with heavy legs, only moderate cold hypersensitivity was significantly associated with varicose veins (OR 0.519, 95% CI 0.290 to 0.926) and not severe cold hypersensitivity (OR 0.999, 95% CI 0.636 to 1.569).

The relationships between cold hypersensitivity, heavy legs and varicose veins are shown in table 5.

The reference group had non-heavy legs and no cold hypersensitivity; the OR of non-heavy legs and moderate cold hypersensitivity was 1.799 (95% CI 1.434 to 2.258) and that of non-heavy legs and severe cold hypersensitivity was 2.183 (95% CI 1.743 to 2.734). Similarly, heavy legs and no cold hypersensitivity were associated with a higher risk of varicose veins than the reference group (OR 6.879; 95% CI 5.041 to 9.387). A similar association was observed in heavy legs with moderate cold hypersensitivity (OR 2.583; 95% CI 2.121 to 6.053) and severe cold hypersensitivity (OR 7.135; 95% CI 4.980 to 10.221).

Discussion

We examined the frequently overlooked symptoms of cold hypersensitivity and heavy legs related to varicose veins in a large sample and found that patients with varicose veins exhibit notable sensations of extremity heaviness and coldness compared with those without this condition. In clinical practice, the sensation of coldness is usually relegated to a secondary position among the many varicose vein symptoms. This relegation is attributed to its subjectivity and the consequent ease with which it can be overlooked. However, our study showed the presence of a moderate-to-severe degree of hypersensitivity to cold in the lower extremities, which has hitherto been underestimated as a subjective symptom associated with varicose veins. Of note is the significance of the concurrent symptoms of heaviness and cold feet. When these symptoms coexist, the likelihood of confirming the presence of varicose veins is notably amplified compared with individuals without such symptoms. To date, no direct empirical evidence or animal studies have been conducted to elucidate these specific relationships of symptom and disease, so our study could provide novel findings. It may be that the extracellular matrix remodelling in varicose veins contributes to subsequent venous hypertension.8 Under physiological circumstances, the presence of venous dilation while under a dependent position instigates the venous–arterial reflex, inducing a subsequent contraction response within the arteries. This reflex mechanism counteracts precapillary resistance and venous hypertension, reducing blood flow through the microvessels. Through these concerted actions, a harmonious equilibrium of venous blood flow is maintained.9 10 As a consequence of this physiological reaction, the body experiences the sensation of cold feet owing to the sequential response of arterial vasoconstriction. Over time, this phenomenon can be exacerbated, resulting in the progressive intensification of the cold sensation. Furthermore, Asians have notably narrower diameters of the great saphenous vein than their Caucasian counterparts. Venous distal reflux frequently extending down to the ankle level was observed in one study among many in an Asian patient cohort.11 The presence of an increased frequency of venous blood reflux may cause heightened activity of the venoarterial reflex. Finally, blood stasis and local hypoxia resulting from varicose veins may stimulate unmyelinated C-fibres in the vicinity of the saphenous veins. This phenomenon may contribute to the local disruption of cold sensation regulation.12 13

A recent questionnaire-based study of 1120 patients found that coldness was significantly higher than other symptoms in patients with varicose veins.7 Moreover, there was a significant correlation between the varicose vein diagnosis and coldness (r=0.47, p<0.001).7 Among the 495 patients complaining of coldness, 70% had heavy legs.14 Additionally, a feeling of heaviness was positively associated with varicose veins primarily in females patients (OR 2.6, 95% CI 2.1 to 3.3). Moreover, as the severity of varicose veins progressed, the feeling of heaviness showed a stronger association with the varicose veins diagnosis, with OR of 1.4 (95% CI 0.9 to 2.2) in C1 patients and OR 4.8 (95% CI 1.6 to 14.6) in C5–C6 patients.14 However, there is a lack of advanced investigations into the association between cold hypersensitivity, heavy legs and varicose veins in the existing literature. The present study provides more information about this issue (table 5), indicating that the diagnosis of varicose veins is more accurate as long as there is a higher proportion of the coexistence of heavy legs and moderate cold hypersensitivity (OR 3.583; 95% CI 2.121 to 6.053) and severe cold hypersensitivity (OR 7.135).

Varicose veins frequently cause various symptoms in the lower limbs, including sensations such as heaviness, swelling, aching, restlessness, cramps, itching and tingling.14 15 These abnormal vessels represent a chronic and advanced condition that exerts a substantial and discernible influence on the patient’s overall quality of life. These varices can lead to subsequent complications including superficial vein thrombosis, deep venous insufficiency, arthrogenic congestive syndrome and a propensity for bleeding arising from variceal sources. According to the findings from the Edinburgh Vein Study conducted over 13.4 years, a substantial proportion of individuals (57.8%) who presented with varicose saphenous veins or chronic venous incompetence showed a progressive deterioration in their varicose vein condition throughout their lifetime.16 Close to one-third of individuals with varicose veins experience skin changes associated with chronic venous insufficiency, rendering them susceptible to skin ulcers in the lower extremities. The advancement of chronic venous disease should not be underestimated, underscoring the need for timely interventions to impede disease progression. These interventions are advantageous for the patient’s well-being and could reduce the overarching expenses associated with medical services.

The sensation of cold hypersensitivity in the hands and feet is associated with factors such as hypertensive vasoconstriction, stress,17 inadequate physical activity and a specific bodily constitution (called the cold pattern of the Sasang constitution).18 Moreover, this particular trait displays an evident hereditary component.4 Depending on the underlying cause of cold hypersensitivity, distinct treatment approaches should be considered. These range from conservative strategies involving physical therapy and using insulated clothing to more invasive options including lumbar interventions.19 20 In individuals with varicose veins accompanied by sensations of coldness, many supplementary leg-related symptoms usually coexist. These encompass sensations of heaviness, pain, the subjective perception of swelling and cramps. These manifestations can collectively exert considerable influence on an individual’s day-to-day activities and social engagement, causing physical and psychological fatigue and substantial inconvenience.

The introduction of efficacious treatment protocols targeting varicose veins can mitigate the symptoms associated with cold hypersensitivity and its accompanying manifestations, possibly enhancing overall clinical outcomes.

Healthcare providers frequently underestimate the gravity and implications of varicose veins, leading to their neglect, and there is usually a gap in understanding the comprehensive spectrum of linked symptoms. Therefore, emphasising the significance of varicose veins, particularly considering the substantial population affected by this condition, is crucial. For patients developing varicose veins and other cardiovascular diseases, history-taking and physical assessment are important factors to identify the pathophysiological process.21 Common symptoms such as oedema, leg pain and skin changes can easily be reported from self-check-up by patients.21 The assessment of a self-reported approach has been validated by a large study including 10 423 adult participants, with their severities of varicose veins defined by using self-reported venous symptoms.22 Self-reported symptom assessment focusing on the leg is a simple and practical method which can be applied to a real-world setting.23 The pronounced socioeconomic burden stemming from advanced forms of varicose veins further underscores the need for heightened awareness and proactive management.

Conclusion

This study presents findings based on the largest sample of patients with varicose veins to date, indicating that these patients show notable sensations of extremity heaviness and coldness, ranging from moderate to severe, compared with individuals without this condition. When assessing patients clinically, complaints pertaining to moderate to severe degrees of coldness should be regarded as a potential symptom of varicose veins, particularly in the absence of arterial disorders. The identification of supplementary leg symptoms linked to varicose veins has significant clinical value, given the relatively limited diagnostic efficacy of venous leg symptoms reported in the existing literature. The legs can be a clue to the heart, and symptoms related to varicose veins could be confused or be coexistent with undetected heart failure.24 There are many communal pathophysiology mechanisms between varicose veins and other cardiovascular diseases, such as inflammation, endothelial dysfunction and thrombosis.24 Furthermore, the genetic correlation between varicose veins and heart failure has been reported in a recent article,25 indicating a higher risk of heart failure in patients with varicose veins.25 Either cold hypersensitivity or heavy legs is a subjective description. Patients with varicose veins have a double risk of congestive heart failure, deep vein thrombosis and pulmonary embolism.25 However, early surveillance is difficult for currently limited medical competence and resources. As a result, self-reported symptom assessment focusing on the leg can be a simple and practical method to approach the progress of varicose veins.23 Awareness of patient-oriented common complaints including cold hypersensitivity and heavy legs can provide more details for early detection and differential diagnosis, which can mitigate the drawbacks of current clinical settings and identify more cases at the early stage of varicose veins. The concurrent manifestations of leg heaviness and pronounced cold sensation can serve as pivotal markers suggestive of latent varicose veins, empowering healthcare practitioners to make informed decisions in their routine clinical practice. These symptoms provide vital diagnostic clues and contribute to enhanced varicose vein diagnosis and management protocols, leading to an improved quality of life for these patients.