HOW TO MANAGE OUTPATIENTS WITH DEEP VEIN THROMBOSIS
 Achkar A, Samama MM.
Journal des Maladies Vasculaires 1999; 24(1):58-65

COMMENTARY BY:
Henri Boccalon, M.D., Ph.D.
Toulouse, France

This presentation discusses different ways in which ambulatory treatment of deep venous thrombosis (DVT) can be carried out. It is the advent of low-molecular-weight heparins that allow outpatient management. Thus, the treatment is more comfortable for the patients and also for medical personnel. The cost of treatment is reduced and control of hemodynamic parameters simplified. The in-hospital stay can be reduced or even eliminated. Clinical trials now underway raise the possibility of treating pulmonary embolism on an outpatient basis as well.

With regard to the diagnosis of DVT, Doppler duplex ultrasound can be accepted because it is noninvasive and has a comparable sensitivity and specificity to venography. The latter has almost disappeared in clinical practice. This article does not address the problem of DVT recurrence and there is no clear and reliable way to manage this problem. The question arises "Do we need to hospitalize the patient or do we need to initiate a search for the etiology of the thrombosis?"

The authors of this presentation insist on absolute obligation to confirm the diagnosis of deep venous thrombosis before starting anticoagulant treatment. A single exception is granted if the clinical probability of DVT is high and there is need to wait for a duplex examination or the results of a D-dimer assay.

The hemorrhagic risk of anticoagulant therapy is still too high. I would like to point out that France does not insist on every center having an anticoagulant clinic. In Toulouse, we set up such a clinic in 1998. There we succeeded in reducing by 50% iatrogenic complications of anticoagulant therapy. This has been achieved by teaching the patient and the medical network their individual responsibilities with regard to thromboembolic disease and its treatment. It is essential that a specialist center obtain the consent of the general practitioner and the patient's family before treating DVT on an ambulatory basis. Also, in addition to the obligations of monitoring anticoagulant treatment, it is necessary to insure that the patient achieves adequate compression therapy.

Treatment with low-molecular-weight heparins is now standard practice. Nevertheless, it is advisable not to forget basic principles of anticoagulant therapy. These include monitoring the platelet count and watching for overdose of anticoagulants in the elderly. The search for an underlying etiologic agent should not be forgotten, and during such an investigation it may be necessary to stop anticoagulant treatment.

Treatment of DVT at home is possible if there is no hemorrhagic risk, no symptomatic pulmonary embolism, and if monitoring can be achieved easily. However, an in-hospital stay if necessary can be shortened either by adding an ambulatory element or by a planned 48-hour hospitalization. ivdfboc2







THE POSTTHROMBOTIC SYNDROME IN RELATION TO VENOUS HEMODYNAMICS AS MEASURED BY MEANS OF DUPLEX SCANNING AND STRAIN-GAUGE PLETHYSMOGRAPHY
Haenen JH, Janssen MCH, van Langen H et al.
J Vasc Surg 1999; 29:1071-76

ABSTRACT AND COMMENTARY BY:
Gy–rgy Acsady, M.D.
Professor of Vascular Surgery
Budapest, Hungary

In this study, venous hemodynamics were evaluated in 82 patients 7 to 13 years following deep venous thrombosis (DVT). The initial DVT was diagnosed by phlebography. All patients had been treated with intravenous heparin for five to ten days during the acute phase and with oral anticoagulants for at least 12 weeks. All had been instructed to wear graduated compression stockings. In followup, local venous compressibility, reflux, and the presence of flow were assessed by color-flow duplex scanning. Venous resistance in the postthrombotic extremity was measured by strain-gauge plethysmography.

The veins examined included the common femoral, superficial femoral (proximal, middle, distal), long saphenous (proximal, middle, distal), popliteal, short saphenous, posterior tibial, anterior tibial, peroneal, and gastrocnemius. Proximally, reflux was evaluated after a Valsalva maneuver. Reflux in the distal veins was detected by distal manual compression with sudden release. Pathological reflux was defined as reverse flow duration in the proximal veins > 1 second and in the distal veins > 0.5 seconds. Superficial or deep reflux was defined as the presence of abnormal venous reflux in at least one vein segment and combined reflux in at least two vein segments. The vein was considered incompressible when it was not totally compressed under gentle pressure by the duplex probe.

Relationship between the seven-point CEAP scale and the presence of abnormal venous resistance and body mass index (BMI) was analyzed by the chi-square test. The contribution of age, gender, presence of reflux, and venous resistance in relation to the seven-point CEAP scale was studied with simple regression analysis. Important results were:

  1. There was no significant relationship between the CEAP class and the BMI.

  2. Prevalence of abnormal venous resistance was not significantly greater in patients with severe clinical symptoms of postthrombotic syndrome.

  3. A total of 64% of patients with severe signs of postthrombotic syndrome had a combination of deep and superficial reflux.

  4. No relationship was found between postthrombotic syndrome and incompressibility of major veins nor with a combination of reflux and incompressibility.

  5. Only reflux was shown to have a significant relationship to the CEAP classification. Reflux in the proximal and distal superficial femoral veins and popliteal veins was associated with a significantly higher mean CEAP classification. No such significant relationship was found in the tibial, long and short saphenous vein.

  6. Age and reflux appeared to be the main contributors to the severity of postthrombotic syndrome.
COMMENTARY

In my opinion, the late consequences of acute deep venous thrombosis depend on the time which has elapsed between the onset of symptoms and the beginning of therapy as well as extension of the acute venous occlusion. Late sequelae are also influenced by the type of initial therapy (anticoagulant, fibrinolytic, or surgical). Late changes of chronic venous insufficiency (CVI) are related to adequacy of the drugs given, duration of treatment time, quality of followup treatment, and, of course, cooperation of the patient.

These factors determine both the extension of initial thrombus and the degree of recanalization which in turn influences the development of venous hypertension. Ultimately, the severity of the postthrombotic syndrome depends on the quantity and duration of venous hypertension.

In this manuscript, the authors examined several hemodynamic factors by various methods in 82 patients treated with conventional anticoagulant therapy. Their results document the known pathological role of late consequences of DVT in the development of symptoms of postthrombotic syndrome; however, they did not uncover any new information. ivdfacs1







VENOUS THROMBUS STABILITY DURING ACUTE PHASE OF THERAPY
 Caps MT, Meissner MH, Tullis MJ et al.
Vascular Medicine 1999; 4:9-14

COMMENTARY BY:
David S. Sumner, MD
Distinguished Professor of Surgery Emeritus
Southern Illinois University School of Medicine
Springfield, Illinois

This prospective study was designed to document the incidence of contiguous and noncontiguous extension of deep venous thrombosis (DVT) during the early phase of medical treatment and assess the effect of anticoagulation levels on the risk of thrombus extension.

Seventy-one patients with acute lower extremity DVT were enrolled. Those with a prior history of DVT or with clinical evidence of postthrombotic disease were excluded. After the initial diagnostic study, all patients underwent 3 to 7 repeat duplex examinations during a three-week period. Length of followup ranged from 2 to 21 days (median 15). All duplex exams were performed at the University of Washington Vascular Research Laboratory and included scans of all veins of both legs from the inferior vena cava to the ankle. Anticoagulation and other aspects of therapy were managed by the patient's primary care physician. Anticoagulation levels were considered adequate if the INR equaled or exceeded 2.0, or if the PTT was 55 seconds or longer.

Thirteen patients (18%) presented with isolated calf vein thrombosis and 31 (44%) had iliofemoral involvement. Extension of the initial thrombus occurred in 15 (21%). Five of these were not contiguous with the original thrombus. Three were new thrombi in the previously uninvolved leg. Extensions were more frequent in the early therapeutic period with the cumulative incidence being 13% at five days and 26% at three weeks (Kaplan-Meier analysis). A total of 9 (60%) of the extensions were asymptomatic. Two patients with new iliac and femoral vein thrombi had pulmonary emboli, one of which was fatal. Age, sex, malignancy, recent surgery, prolonged bedrest, and proximal location of the thrombus were not significantly related to the incidence of thrombus extension.

Three patients with isolated calf vein thrombi and one with a contraindication to anticoagulation received no heparin or Coumadin. Thirty-five patients (49%) were adequately anticoagulated less than 80% of the time. At three weeks, these inadequately treated patients had a 38% cumulative incidence of recurrent DVT. In contrast, the cumulative incidence of recurrent DVT at three weeks was considerably less (14%) in the 36 patients adequately anticoagulated 80% or more of the time. By the Cox Proportional Hazards Regression Analysis, each 20% reduction in the time of adequate anticoagulation was associated with a 1.4-fold increase in the incidence of recurrent DVT, a ratio that increased to 1.5 when adjusted for the presence of other risk factors.

COMMENTARY

The goal of anticoagulant therapy for acute DVT is to prevent further thrombus formation, to facilitate natural thrombolytic processes, and to prevent pulmonary emboli. By decreasing the incidence of clot propagation and encouraging clot lysis, the extent of damage to venous valves is decreased, thereby reducing the risk of subsequent postthrombotic syndrome. This study, however, suggests that these goals are often not achieved in clinical practice. In fact, the authors found that the incidence of clot extension in patients being treated by primary care physicians in the mid-1990s in a medically sophisticated community was surprisingly high during the three-week period following initial diagnosis of lower extremity DVT. That the incidence of clot extension was several times greater in this study than previously reported can be attributed, in part, to the superior sensitivity of duplex scanning which exceeds 90% and approaches 100%, to the completeness of the venous survey, and to the skill of the vascular technologists. In addition, past studies were often confined to symptomatic patients. If this had been the case in the present study, more than half of the patients with new thrombi would have been overlooked.

The observation that nearly half of the patients were inadequately anticoagulated is disturbing but not unexpected. Despite concerted educational efforts, many physicians are unduly cautious in the administration of heparin, especially in the critical early period following the onset of DVT. This practice may be partially responsible for skewing the incidence of recurrent clots to the initial 5 to 7 days after diagnosis. An encouraging finding was the verification that adequate anticoagulation does reduce the incidence of recurrent thrombosis by more than 60%. However, the 14% incidence of thrombus extension at three weeks is far from ideal.

To determine the percent of time that patients were inadequately anticoagulated, the authors interpolated between INR and PTT data points plotted as a function of time. Depending on the length of time between data points and the physician's policy for ordering heparin doses, this practice could over- or underestimate the time of adequate anticoagulation. vdsum201







RISK FACTORS FOR VENOUS THROMBOEMBOLISM FOLLOWING PROLONGED AIR TRAVEL: A "PROSPECTIVE" STUDY
 Arfvidsson B, Eklof B, Kistner RL, Masuda EM, Sato D
Vasc Surg 1999; 33(5):537-44

COMMENTARY BY:
Prof. Lars Norgren
Lund, Sweden

After their first publication on venous thromboembolism associated with prolonged air travel,1 the authors performed this study on hospital inpatients with deep vein thrombosis and/or pulmonary embolism in whom a relation to air travel could be found. During slightly more than three years, 109 patients were identified with venous thromboembolism (VTE). Of these, 25 had a history of recent air travel (14 women, 11 men, age range 36 to 79 years, airborne for 5 to 18 hours). Twenty of 25 patients developed symptoms within the first 24 hours after starting the flight. The other 5 developed symptoms within 2, 3, 7, 9, and 10 days. All 25 patients had deep vein thrombosis and 9 had pulmonary embolism as well. The thrombus was confined to the leg in all but 7 who had an iliac vein thrombus.

The majority of patients (92%) had at least one patient-related risk factor (mean of 3). Overweight was the most common 76%, chronic heart disease 44%, hormone medication 40%, chronic disease excluding heart disease and malignancy 32% history of previous venous thromboembolism 28%, malignancy 28%, smoking 20%, recent lower limb injury 16%, and recent surgery 12%. The authors concluded that flight travel was not important as a risk factor in healthy individuals but that a combination of patient-related risk factors and cabin-related risk factors (cramped position and slight dehydration) could be of importance. They provide precautions for passengers with risk factors, including anticoagulant prophylaxis with low-molecular-weight heparin (LMWH), compression stockings if there is tendency to swelling, intermittent walking, deep breaths while seated, and nonalcoholic beverage consumption.

COMMENTARY

This report follows a previous report from the same group. As the authors state, this study is as prospective as was possible. Nevertheless, it does not give any information on the total incidence of VTE after long flights.

There are some interesting discrepancies between the two studies in that chronic disease or malignancy was seen in only 25% in the previous study but constituted 60% in the present study. There is a great difference between hormone medication in the two studies (16% and 40%). Most importantly, the first study did not tell us anything about obesity which was present in 76% in the present study.

In this study, smoking is reported as a risk factor in 20%. This is a rather controversial issue since smoking has not been regarded as a risk factor for VTE. Actually, contradictory findings were present in a study from the UK published in 19782 where there was a reduced incidence of DVT with increasing levels of cigarette smoking. On the other hand, in a report from 1986,3 cigarette smoking in conjunction with surgical procedures was found to be of some risk. Finally, in a study from 1995,4 it was not possible to draw a firm conclusion concerning smoking.

The latter study also discussed the role of obesity, finding that an increased body mass index was an independent risk factor for VTE which is in line with the study reported above. There are also contradictory findings. The Journal of the Royal Society of Medicine 5 concluded that obesity was a risk factor for thrombosis after air travel while a recent summary from the Aviation Health Institute claimed that obesity is not a clear risk factor.6 This review article also accepted smoking as a degree of protection against VTE.

Discrepancies between various studies shows how difficult it is to perform this type of study. There is regularly a selection bias because large numbers of patients with DVT go without symptoms and it is not possible to get correct figures for DVT after flights or any other risky situation. Most studies appear to conclude that the risk for healthy patients to develop VTE after long flights is very limited while those with known risk factor should take precautions. The precautions listed in this paper do not seem controversial except for LMWH in patients with one or more risk factors. One needs to be careful when offering this kind of prophylaxis. Young females on hormone medication probably do not need prophylaxis. While single risk factors should not qualify for pharmacological prophylaxis, combinations of risks is a trickier situation.

FInally, the authors claim that only 23% of patients with VTE had a long flight which might be part of the VTE etiology. As the study was performed in Hawaii, it could be argued that a considerable proportion of patients with any diagnosis had recently had a long-distance flight. ivdfnor3

REFERENCES

1. Eklof B, Kistner Recently, Masuda EM, Sonntag BV, Wong HP. Venous thromboembolism in association with prolonged air travel. Dermatol Surg 1996; 22:637-41.

2. Prescott RJ, Jones DR, Vasilescu C, Henderson JT, Ruckley CV. Smoking and risk factors in deep vein thrombosis. Thromb Haemost 1978; 40:128-33.

3. Sue-Ling HM, Johnson D, McMahon MJ, Philips PR, Davies JA. Preoperative identification of patients at high risk of deep venous thrombosis after elective major abdominal surgery. Lancet 1986; 1:1173-76.

4. Venous thromboembolic disease and combined oral contraceptives: Results of international multicenter case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1995; 346:1575-82.

5. Forbes CD, Johnson RV. Venous and arterial thrombosis in airline passengers. J Royal Soc Med 1998; 91:565-66.

6. Giangrande PLF. Thrombosis and air travel. Aircare Worldwide 1999; UK.







RISKS OF AND PROPHYLAXIS FOR VENOUS THROMBOEMBOLISM IN HOSPITAL PATIENTS
Second Thromboembolic Risk Factors (THRiFT II) Consensus Group
Phlebology 1998; 13:87-97

ABSTRACT AND COMMENTARY BY:
David Bergqvist, M.D., Ph.D.
Professor of Vascular Surgery
Department of Surgery, Uppsala University
Uppsala, Sweden

The British Second Thromboembolic Risk Factors (THRiFT II) Consensus Group has reported an analysis of published papers during a period from 1991 to 1997 as identified by a Medline search and the participants' knowledge of the literature. In their analysis, they used only papers reporting randomized trials with clearly defined diagnostic methods and clear endpoints.

Frequency of venous thromboembolism in various specialties is summarized. Guidelines for thromboprophylaxis based on the published evidence and consensus opinion within the group are given. In most situations, subcutaneous administration of low-molecular-weight heparins once daily is recommended. There is overwhelming evidence of that prophylaxis reduces the incidence of postoperative deep vein thrombosis and fatal pulmonary embolism. Prophylaxis has major practical advantages and is cost effective. Further work is required to investigate the use of thromboprophylaxis in minimal access surgery, trauma, elective lower limb surgery, hip fracture, and pregnancy. Also, further work is needed to investigate the risk of thromboembolism associated with contraceptive pills and hormone replacement therapy, to compare the efficacy of low-molecular-weight heparins and mechanical methods, and to investigate the need for extended post discharge prophylaxis. The development of local hospital prophylaxis protocols is strongly recommended. Monitoring protocol compliance and the adverse reactions should be a part of a clinical audit.

COMMENTARY

The literature on postoperative thromboembolic problems has become overwhelming and almost too extensive to grasp, even for specialists in the field. This, together with movement into the era of evidence-based medicine has made various types of consensus activities necessary and welcome. One potential problem, however, is the definition and process of consensus. Originally started by the National Institutes of Health (and thereafter taken up in several countries), the idea was to establish a document with a certain degree of authority with the blessing of national health care authorities. Eventually, the consensus concept has become diluted and used by various discussion groups. This does not necessarily mean differences in conclusions but rather in the impact of the document. This principle observation is not meant to question the value of the THRiFT II document but instead merely to comment on the fact that the process and any potential official influence are not made clear in this article.

Until now, most studies on thromboprophylaxis have used deep vein thrombosis as a surrogate endpoint for clinical thromboembolism. Now we need to know more what that means. Of course, it is hard to believe that without thrombosis there will be no pulmonary embolism and without pulmonary embolism there will be no mortality.

One of the major problems in analyzing the effect of prophylaxis on fatal pulmonary embolism (this is not discussed in the present article) is the importance of the autopsy rate. If we are interested in total mortality, the required sample size of future studies will make most impossible to perform. In the present article, the background (frequency of thromboembolism without prophylaxis) is given although it is stated that the frequency of deep vein thrombosis in hip surgery is unknown. Actually, there are several phlebographic studies pointing to an incidence of at least 50%.

In this paper, the various types of prophylaxis in various clinical situations are adequately dealt with. The final conclusion is that low-molecular-weight heparins should be used in most of these situations. I would strongly support their recommendation to develop local multidisciplinary protocols. My experience in Sweden is that the existence of such protocols increases the use of prophylaxis in high-risk patients and also increases the compliance.

Extended or prolonged prophylaxis extending to more than five or ten days is briefly discussed in this paper, and I do agree with the authors that our knowledge is very superficial at present regarding this. My personal guess is that some patients operated on for malignant diseases are in greater need of extended prophylaxis than orthopedic cases.

One current problem, which is only mentioned in this manuscript, is the combination of thromboprophylaxis and epidural analgesia in obstetrics. Finally, although complications are extremely rare, an increasing number of colleagues have become restrictive in thromboprophylaxis because of the severity of bleeding complications. When they do occur, they can be serious and may be important for medicolegal reasons. The article ends with a list of examples of further studies which are necessary to extend our knowledge. Some of the problems are already on the way to be solved in ongoing studies. ivdfber2







NONINVASIVE DIAGNOSIS OF VENOUS THROMBOEMBOLISM IN OUTPATIENTS
 Perrie A, Desmarais S, Miron P, de Moerloose P, Lepage R, Slosman D, Didier D, Unger PF, Patenaude JV, Bounameaux H
Lancet 1999; 353:190-95

COMMENTARY BY:
Marc Cairols, MD, FRCS (Eng)
Barcelona, Spain

The authors have tried to establish an integrated diagnostic algorithm based on clinical probability assessment of venous thromboembolic disease, including deep venous thrombosis (DVT) and pulmonary embolism (PE). In addition to clinical diagnosis, the authors give plasma D-dimer measurement a key role in ruling out venous thromboembolic disease. Venous compression ultrasonography of the lower limbs was also used to avoid the need for a venogram and to reduce need for pulmonary angiography and lung scan.

A total of 1102 consecutive patients with clinically suspected PE or DVT were considered for study. Only 948 entered into the sequential diagnostic protocol. All were attended to in an emergency center or in an outpatient clinic at the Geneva University Hospital in Switzerland or the HŮpital Saint-Luc in Montreal, Canada for a one-year period. Patients in whom venous thromboembolism was deemed absent did not receive anticoagulation and were followed for three months.

A normal D-dimer concentration (< 500 ug/L by a rapid ELISA assay) ruled out 286 patients (31%) as not having venous thromboembolism. The other 532 patients had plasma D-dimer > 500 ug/L. In 157 of these (17%), compression ultrasonography established the diagnosis of DVT. Thus, there were 475 patients with no DVT on ultrasonography, 238 with suspected DVT, and 237 with suspected PE. In the DVT cohort, 236 (26%) had a low or intermediate probability of DVT on clinical assessment, and the duplex scan was negative. The two patients with high probability of DVT had a positive phlebogram. In the PE cohort, 37 (4%) had a normal or near-normal lung scan. A total of 43 (5%) had a high probability of PE on the lung scan. In 50 cases with high probability of PE, a pulmonary angiography was performed. In 13 (26%), pulmonary angiography showed the presence of PE. Angiography proved negative in the other 37 (74%).

The authors conclude that a diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan produced a noninvasive diagnosis in the vast majority of patients with suspected venous thromboembolism in an outpatient setting.

COMMENTARY

It is well known that clinical diagnosis for DVT is like tossing a coin. Different patient referral criteria from diverse health systems produce different populations. In this study, for example, only the cohort from Geneva is given and only 17% of cases were confirmed to have a diagnosis of DVT. In other words, to identify a true DVT, six other individuals were examined. Perhaps the referral criteria were too liberal.

Plasma concentration of D-dimer used to rule out venous thromboembolism seems to be reliable. However, determination of D-dimer plasma concentration is not a standardized test. On the contrary, each antibody may measure different fragments. It should be run with a dedicated analyzer and this is not the case in every laboratory. Determining the lowest cutoff level may be controversial. The poor sensitivity at the crucial region of the calibration curve may raise concern. Nevertheless, other studies support the discriminating level of 500 ug/L as the best.

Of the 286 patients (31%) with low and intermediate probability scans, some may have had infrapopliteal DVT which might have produced a minor thromboembolic event. If referral criteria were more restrictive, could performing a duplex scan as a screening test be of value? In our emergency unit, 65% of patients with suspected DVT have a positive duplex scan.

A major issue is duplex scan diagnostic technique. Years ago, Strandness proved that compression is not an ideal technique for diagnosing DVT.1 He believed flow characteristics remained the best parameter. Fresh clot can be compressed and yet have no flow. In the present study, it would have been interesting to know the reliability of this method in diagnosing DVT.

Degrees of probability are acceptable for lung scan classification but I am not sure the same classifications can be applied for DVT in the legs. Clinical syndromes are individually dependent. For example, some patients with associated diseases may have plasma D-dimer concentration altered by the primary condition.

Also, one wonders about the accuracy of a telephone call to confirm a thromboembolic event. I believe that a further patient examination should have been done. Despite ruling out venous thromboembolism, 39 of 703 patients (5.5%) received anticoagulation and, for other reasons, 184 of 1102 (17%) were initially excluded from the study. In addition, 64 patients were excluded because the diagnostic protocol was not followed strictly (40 patients with suspected PE should have had angiography and 14 patients with suspected DVT should have had phlebography). Thus, a total of 27% of patients did not follow the protocol.

Introducing protocols in day-to-day work is a laudable target. While plasma D-dimer concentration has an excellent negative predictive value, its specificity is very low. Dealing with venous thromboembolism is not simple and it is important that no patient requiring treatment be excluded because a proper diagnosis was not made. ivdfcai1

REFERENCE

1. Strandness D. Deep venous thrombosis and postthrombotic syndrome. In: Duplex Scanning in Vascular Disorders. Raven Press, New York 1993; pp 240-42.







MINI ABSTRACTS
John J. Bergan, M.D.
Items of Interest Which Have Crossed the Editor's Desk
(Provided for reference purposes and general interest)


Graduated Compression Stockings in the Prevention of Thromboembolism
Agu O, Hamilton G, Baker D.
Br J Surg 1999; 86:992-1004

This review of 15 randomized and controlled trials comes to the conclusion that the effect of the gradient stockings is enhanced by combinations with pharmacologic agents.


Edema Volume, Not TIming, is the Key to Success in Lymphedema Treatment
Ramos SM, O'Donnell LS, Knight G.
Am J Surg 1999; 178:311-15

In this study of 69 women treated by combined decongestive therapy, the best results were achieved in limbs with the least initial volume of edema. Not surprising.


Leg Cramps in the Elderly: Prevalence, Drug and Disease Associations
Abdulla AJJ, Jones PW, Pearce VR
Int J Clin Pract 1999; 53(7):494-96

This study identifies a prevalence of leg cramps at 50%. These are more common in women than men and occur most often at night. They were strongly associated with peripheral vascular disease and arthritis but negatively associated with heart failure, hypertension, diabetes, and stroke. Unfortunately, peripheral vascular disease was not separated as to arterial or venous. Readers of the Venous Digest, of course, know that leg cramps are associated with venous insufficiency.