Varicose Veins and Risk Factors: Systematic Review with ☸️SAIMSARA.

• Generated: 2026-02-15 11:05:20 CET
• Plan: Pro (expanded craft tokens; source: Europe PMC)
• Source: Europe PMC
• Scope: Titles/Abstracts (tiab)
• Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
• Total Abstracts/Papers: 8600
• Downloaded Abstracts/Papers: 7850
• Included original Abstracts/Papers: 716
• Total study participants (naïve ΣN): 8321642

• Bias: Qualitatively inferred from study design fields.

• Demographic Risk Factors:
• Age: Increasing age is a consistent risk factor for VVs [7, 13, 91, 114, 145, 149, 184, 195, 235, 252, 258, 260, 275, 291, 303, 304, 313, 336, 349, 350, 358, 373, 378, 384, 385, 409, 411, 422, 440, 464, 486, 487, 489, 491, 492, 500, 505, 518, 567, 576, 577, 579, 613, 616, 626, 631, 640, 643, 701, 707, 712], with older patients often presenting with more advanced disease [336, 411].
• Sex: Female sex is frequently associated with VVs [7, 9, 10, 13, 72, 76, 78, 91, 114, 135, 145, 147, 149, 184, 195, 220, 241, 258, 260, 267, 275, 291, 294, 303, 313, 336, 349, 355, 358, 375, 398, 400, 422, 440, 464, 473, 477, 486, 489, 491, 492, 500, 505, 518, 527, 563, 567, 579, 611, 616, 626, 627, 631, 632, 639, 640, 647, 652, 653, 689, 696, 703, 706, 707, 711], with women having up to 7 times higher risk than men [358]. However, some studies note higher prevalence in men for trunk varices [464] or more severe disease [336].
• Body Mass Index (BMI) / Weight / Height: Higher BMI and obesity are significant risk factors [7, 13, 34, 36, 68, 78, 89, 91, 110, 118, 121, 149, 174, 181, 182, 188, 220, 223, 231, 235, 243, 248, 258, 263, 274, 298, 303, 304, 314, 320, 325, 342, 349, 350, 355, 358, 373, 381, 384, 385, 415, 420, 422, 424, 432, 434, 440, 471, 473, 489, 492, 506, 518, 526, 567, 569, 586, 588, 593, 609, 611, 613, 631, 634, 637, 689, 696, 701, 707], with higher BMI associated with increased complication rates [3] and less improvement post-treatment [118]. Taller height is also associated with increased risk [13, 89, 110, 349, 355, 611].
• Lifestyle & Occupational Factors:
• Prolonged Standing/Static Postures: Consistently identified as a significant risk factor [9, 66, 72, 91, 105, 138, 163, 175, 182, 195, 207, 235, 242, 273, 277, 287, 294, 349, 362, 375, 409, 432, 440, 473, 476, 489, 502, 506, 527, 552, 566, 577, 582, 611, 614, 627, 643, 646, 647], with some studies reporting high odds ratios (ORs) up to 27.44 [105] or 31.8 [287] in specific populations.
• Physical Activity/Sedentary Lifestyle: Lack of exercise increases risk [48, 81, 138, 155, 391, 526, 545, 611, 646], while regular exercise can be protective [94, 155]. Sedentarism is a risk factor for recurrent varices [391] and leg edema [426].
• Smoking & Alcohol: Smoking is associated with increased risk [7, 89, 138, 249, 266, 312, 410, 424, 434, 518, 545, 569, 611, 637, 672, 707] and impaired endothelial function [672]. Mild/regular alcohol consumption may be associated with lower risk [151], but other studies suggest increased risk [249].
• Genetic & Familial Predisposition:
• Family History: A strong and consistent risk factor [7, 29, 36, 48, 70, 73, 91, 128, 181, 209, 228, 238, 244, 271, 287, 291, 294, 349, 385, 432, 440, 465, 473, 477, 489, 491, 498, 502, 504, 526, 560, 564, 597, 616, 633, 643, 657, 659, 688, 703], with genetic factors contributing significantly to familial transmission [238, 465, 597].
• Specific Genetic Variants: Multiple genetic loci and variants are associated with VVs, including PTPRB [15], HADHA, BCL2L1, PARK7 [16], CASZ1 [39, 224], KRTAP5-AS1, PLEKHA5, CBWD1, CRIM1 [44], IRF3, LUM, POSTN, RSPO3, SARS2 [45], PIEZO1 [92, 413], EFEMP1 [83, 99], GJD3 (protective) [64], and MHC class III genomic region [172]. Genetically predicted higher sex hormone-binding globulin (SHBG) levels also increase risk, especially in females [46, 267].
• Hormonal & Reproductive Factors:
• Pregnancy & Parity: Pregnancy is a significant risk factor for VVs development and recurrence [7, 72, 81, 88, 91, 113, 114, 116, 124, 128, 131, 136, 164, 178, 195, 196, 214, 216, 228, 259, 268, 269, 278, 291, 294, 295, 306, 313, 324, 349, 362, 365, 399, 422, 427, 429, 432, 456, 461, 473, 477, 486, 489, 493, 501, 507, 526, 611, 652, 698, 704], with increasing parity being a key factor [116, 124, 195, 313, 349, 432].
• Oral Contraceptives (OCs) & Hormone Replacement Therapy (HRT): Use of OCs is identified as a risk factor in some studies [72, 81, 106, 138, 196, 315, 363, 427, 507, 609, 611, 632, 697], while HRT showed an increased risk in one study [313].
• Comorbidities & Associated Conditions:
• Deep Vein Thrombosis (DVT) / Venous Thromboembolism (VTE): VVs are a significant risk factor for DVT and VTE [19, 55, 58, 87, 93, 102, 104, 107, 109, 111, 113, 117, 120, 127, 130, 134, 135, 143, 144, 145, 150, 155, 164, 171, 176, 177, 181, 185, 188, 191, 194, 201, 205, 206, 215, 217, 223, 225, 226, 230, 232, 241, 243, 248, 254, 260, 261, 262, 263, 264, 265, 266, 268, 272, 279, 283, 292, 297, 304, 314, 315, 322, 327, 329, 331, 333, 338, 352, 353, 356, 361, 363, 365, 367, 370, 373, 376, 377, 379, 380, 383, 386, 387, 389, 393, 395, 399, 405, 415, 421, 423, 427, 434, 441, 442, 450, 451, 458, 459, 460, 461, 482, 493, 496, 498, 499, 504, 505, 507, 510, 513, 517, 518, 521, 522, 524, 525, 528, 532, 533, 536, 538, 540, 542, 544, 550, 551, 554, 556, 557, 560, 569, 570, 571, 583, 585, 586, 587, 588, 589, 590, 594, 596, 600, 601, 602, 603, 605, 606, 607, 608, 609, 612, 613, 617, 618, 619, 620, 621, 622, 625, 628, 629, 630, 631, 635, 636, 638, 641, 642, 645, 648, 649, 654, 656, 660, 662, 667, 668, 670, 671, 674, 675, 676, 677, 678, 679, 683, 684, 687, 690, 692, 693, 694, 697, 698, 700, 701, 702, 705, 707, 708, 709, 710, 712, 713], with ORs up to 5.30 [127] and 16.8 [513].
• Heart Failure & Cardiovascular Disease: VVs are associated with an increased risk of heart failure [13, 30, 38, 43, 145] and other cardiovascular risk factors [348].
• Metabolic Conditions: Hypertension [3, 7, 13, 252], diabetes [3, 7, 36, 71, 97, 410, 424, 426, 545, 704], and dyslipidemia [232, 410] are associated with VVs or their complications.
• Neurological & Cognitive Conditions: VVs are linked to increased incidence of sensorineural hearing loss [22], potential risk for Alzheimer's disease [51], and increased risk of all-cause dementia [95]. Restless legs syndrome (RLS) is associated with VVs [97, 412, 545], though one study suggests RLS may reduce VV risk [152].
• Other Comorbidities: Hydroceles [2], hemorrhoidal disease [33, 234], pelvic varicose veins/pelvic congestion syndrome [31, 204, 372, 429, 516, 549, 578, 633], cirrhosis/portal hypertension [77, 101, 170, 179, 281, 289, 310, 321, 326, 424, 512, 565, 615], cellulitis/infection [3, 40, 42, 48, 90, 160, 162, 170, 175, 279, 302, 417, 480, 519, 534, 542, 604, 613], connective tissue disorders [339, 351, 414, 419, 562, 559, 371], and even schizophrenia [137, 305] have shown associations with VVs.
• Pathophysiological Mechanisms:
• Valvular Dysfunction & Venous Reflux: Central to VV pathogenesis, involving fewer venous valves [21], saphenous vein incompetence [3, 19, 34, 114, 123, 124, 132, 133, 141, 193, 208, 213, 214, 216, 240, 258, 276, 290, 301, 311, 312, 334, 354, 357, 372, 378, 385, 390, 396, 406, 408, 418, 447, 448, 458, 470, 481, 503, 506, 509, 511, 520, 521, 525, 546, 553, 561, 563, 567, 576, 580, 593, 598, 614, 634, 639, 640, 652, 665, 666, 703, 709, 716], and disturbed venous shear stress [35].
• Inflammation & Endothelial Dysfunction: Involves dysregulations in angiogenesis- and inflammation-related factors [40, 42, 62, 63, 123, 129, 266, 280, 282, 300, 302, 316, 322, 332, 359, 364, 366, 397, 401, 402, 453, 472, 484, 488, 530, 574, 584, 610, 614, 672], activation of ETS1-NOTCH4/DLL4 signaling [35], and increased superoxide production [239].
• Hypoxia: Increased activation of hypoxia-inducible factor (HIF) pathway [123, 229, 316, 425, 474, 584] is implicated in VV pathogenesis.
• Extracellular Matrix (ECM) Remodeling: Alterations in smooth muscle cells, collagen, and elastin [397, 401, 445, 453, 539, 584, 650, 665, 703], and increased matrix metalloproteinases (MMPs) expression/activity [123, 332, 343, 366, 453, 472, 584] contribute to vein wall dilation.
• Outcomes & Complications of Varicose Veins:
• Postoperative Complications & Recurrence: Factors like larger vein diameter [132, 213, 214, 231, 320, 553], previous DVT [8, 111, 600], specific surgical techniques [173, 276, 390, 403, 448, 457, 479, 520, 537, 541, 598], and patient characteristics (e.g., male gender [217], advanced age [140], obesity [350]) influence postoperative outcomes and recurrence rates.
• Quality of Life & Functional Impairment: VVs negatively impact quality of life [9, 98, 147, 149, 198, 360, 400, 407, 435, 485, 523, 548, 643], with symptoms like pain and dysfunction [435] and limitations in daily activities [247].
• Ulceration: Risk factors for venous ulceration in VV patients include male sex, obesity, longer VV duration, deep venous valve insufficiency, low lymphocyte counts, high fibrinogen [34], and certain inflammatory markers [63, 155, 274, 342, 396, 467, 487, 561, 598, 663, 680, 686].
• Associated Health Conditions: VVs are linked to various conditions, including hydroceles [2], sensorineural hearing loss [22], breathing difficulties and hypotension [25], heart failure [13, 30, 38, 43, 145], dementia [51, 95], atrial fibrillation [61], mitral valve regurgitation [96], chronic pelvic pain [31, 202], cellulitis [417, 480, 519], and specific thrombophilic factors [205, 232].

• Targeted Screening & Prevention: Given the strong association with age, female sex, and family history [13, 91, 149, 228, 349, 385, 477], screening efforts could be prioritized for individuals with these characteristics.
• Lifestyle Modification: Counseling on modifiable risk factors like obesity [78, 188, 420], prolonged standing [105, 138, 207, 375, 409], and physical inactivity [48, 94, 155] is crucial for both prevention and managing disease progression.
• Comorbidity Management: Awareness of the increased risk for DVT/VTE [127, 130, 191, 230, 331, 461, 513, 569], heart failure [30, 43], and other conditions [22, 95, 202, 416] in VV patients should guide comprehensive patient care and monitoring.
• Post-Procedural Care: Factors influencing postoperative complications and recurrence, such as vein diameter [132, 213, 214, 320, 553], previous DVT [8, 111, 600], and adherence to compression therapy [10, 187, 531], should be integrated into treatment planning and patient education.

• Standardized Epidemiology: Future studies should adopt standardized definitions and reporting metrics for VV prevalence and incidence across diverse populations to enable more robust meta-analyses and comparative studies.
• Mechanistic Pathways: Further research is needed to fully elucidate the complex interplay between identified genetic variants [15, 39, 64, 83, 92], hormonal influences [46, 267], and molecular mechanisms (e.g., inflammation, hypoxia, ECM remodeling) [35, 40, 123, 316, 453] in VV pathogenesis.
• Longitudinal Intervention Studies: Prospective randomized controlled trials are required to evaluate the effectiveness of targeted interventions for modifiable risk factors (e.g., weight management, ergonomic workplace interventions, specific exercise regimens) on the incidence and progression of VVs.
• Risk Stratification Models: Development and validation of comprehensive risk prediction models that integrate genetic, demographic, lifestyle, and comorbidity data are needed to identify individuals at highest risk for VV development and associated complications.

• Heterogeneous Study Designs — The included studies varied significantly in design, from cross-sectional to cohort studies, limiting direct comparisons and meta-analysis.
• Inferred Bias — Bias was qualitatively inferred from study designs, without a formal risk-of-bias assessment for each individual study.
• Variable Outcome Definitions — Definitions and diagnostic criteria for varicose veins and associated conditions were not always consistent across studies, affecting comparability.
• Limited Causal Inference — Many studies identified associations rather than causal relationships, particularly for lifestyle and comorbidity factors.
• Geographic and Ethnic Specificity — Prevalence and risk factor profiles often showed geographic or ethnic specificity, limiting generalizability to broader populations.

• Harmonize Diagnostic Criteria
• Investigate Genetic-Environment Interactions
• Develop Predictive Biomarkers
• Assess Long-term Intervention Efficacy
• Integrate Patient-Reported Outcomes