Table 2.
Main results of the investigations linking HTN and thrombosis in MPNs.
| Author and Year | Study Location | MPN Subtype | Number of Patients | Main Results |
|---|---|---|---|---|
| Carobbio et al. (2011) [42] | International cohort: Italy, Austria, Germany, USA | ET | 891 | HTN, T2DM or smoking (at least one CVRF) were predictors of both major thrombotic events (HR = 1.56, 95% CI = 1.03–2.36, p = 0.038) HTN, T2DM or tobacco use were predictors of major arterial thrombotic events (HR = 1.91, 95% CI = 1.19–3.07, p = 0.007), namely acute myocardial infarction, ischemic stroke, cerebral transient ischemic attacks or peripheral arterial thrombosis, but not of the occurrence of major venous thrombosis (HR = 0.77, 95% CI = 0.33–1.83, p = 0.556), namely venous thromboembolism |
| Buxhofer-Ausch et al. (2014) [43] | Austria | ET, PMF | 167 | HTN prevalence similar in both subgroups (50% vs. 44%, p = 0.48) HTN = risk factor for thrombosis (univariate model: HR = 3.43, range 1.12–10.52, p = 0.03; multivariate model: HR = 3.33, range 0.90–12.29, p = 0.07), in particular arterial thrombosis (only in the univariate model: HR = 3.76, range 1.05–13.48, p = 0.04; multivariate model: HR = 2.79, range 7.06–11.02, p = 0.14) in ET HTN did not impact the occurrence of venous thrombosis (HR = 2.09, range 0.19–23.11, p = 0.55) in ET |
| Pósfai et al. (2015) [44] | Hungary | ET | 101 | HTN = #1 comorbidity (46.5%) in ET HTN not linked to the occurrence of thrombosis in the logistic regression analysis co-existence of two or more CVRFs out of HTN, dyslipidemia, diabetes or smoking was linked to the development of thrombotic events (p = 0.02) thrombosis-free survival lower in ET with ≥ 1 CVRF vs. those without CVRFs (p = 0.01) and in ET patients with one CVRF vs. ≥ 2 CVRFs (p = 0.002) |
| Pósfai et al. (2014) [45] | Hungary | ET | 128 | HTN = predisposing factor (p = 0.001) to the development of thrombotic complications in females with ET of whom ~55% (n = 70) had elevated BP ≥2 CVRFs = linked with elevated probability of suffering a thrombotic event in women diagnosed with ET (RR = 4.728, 95% CI 1.312–17.040, p = 0.01) |
| Horvat et al. (2018) [46] | Hungary | PV, ET, PMF | 258 | HTN and presence of ≥1 CVRF = risk factors for thrombotic events (OR = 2.8, 95% CI 1.6–5.0, p < 0.001; OR = 3.2, 95% CI 1.7–6.3, p = 0.001, respectively), especially arterial thrombosis (OR = 3.3, 95% CI 1.7–6.3, p < 0.001; OR = 5.7, 95% CI 2.3–13.9, p < 0.001, respectively) in PV (n = 70) and PMF (n = 54) the presence of ≥1 CVRF but not HTN alone predicted the development of arterial thrombotic complications (OR = 7.9, 95% CI 1.0–64.9, p = 0.049; OR = 12.2, 95% CI 0.7–225.3, p = 0.044, respectively) both HTN and the presence of ≥1 CVRF were risk factors not only for overall thrombosis (OR = 3.8, 95% CI 1.6–8.7, p = 0.003; OR = 5.1, 95% CI 1.8–14.1, p = 0.001, respectively), but also for arterial (OR = 2.8, 95% CI 1.2–6.5, p = 0.021; OR = 3.9, 95% CI 1.4–11.1, p = 0.009, respectively) and venous (OR = 30.3, 95% CI 1.7–532.4, p < 0.001; OR = 17.1, 95% CI 1.0–300.8, p = 0.005) thrombosis separately in ET |
| Lekovic et al. (2014) [47] | Serbia | ET | 244 | ~58% of ET cases had HTN development of both arterial and global thrombosis associated with HTN (p = 0.01 and p = 0.001, respectively), CVRFs in general (p = 0.01 and p = 0.002, respectively) and number of CVRFs (p < 0.001 and p < 0.001, respectively) |
| Lekovic et al. (2015) [48] | Serbia | ET | 244 | CVRFs (HTN, T2DM and dyslipidemia) and combination of CVRFs and tobacco use were less common in the patients who were still alive at the time of the analysis (~62% versus ~78%, p = 0.05 and ~21% versus ~41%, p = 0.01, respectively) presence of CVRFs (HR = 2.33) and CVRFs + tobacco use (HR = 2.08) linked with shorter overall survival in ET novel assessment tool for the prognosis of ET, namely the Cardio-IPSET prognostic model which takes into consideration the following factors: age, history of thrombotic events, leukocyte count and the presence of CVRFs (HTN, T2DM, dyslipidemia, and smoking) ~75% of deaths in ET attributed to cardiovascular causes |
| Schwarz et al. (2015) [49] | Czech Republic | PV, ET, PMF | 1179 | HTN = predictor of overall thrombosis (p = 0.003), major thrombosis (p = 0.022) and arterial thrombosis (p < 0.001); however, not of microvascular events or venous thrombotic events based on the univariate analysis in MPNs treated with anagrelide in the multivariate regression analysis, HTN was the best predictor of arterial thrombotic events (OR = 1.813, 95% CI 1.295–2.538, p = 0.001) |
| Accurso et al. (2020) [50] | Italy | PV, ET | 403 | HTN = #1 cardiovascular comorbidity in PV and ET (~64%) an elevated percentage of PV vs. ET cases (~39% vs. ~27%, p = 0.014) experienced thrombotic complications CVRFs associated with decreased survival in PV (p = 0.014) and ET (p = 0.036) |
| Cucuianu et al. (2006) [51] | Romania | PV, ET | 37 | ~31% of the patients had HTN association of HTN, platelet count > 600,000 platelets/mmc and hematocrit > 55% was linked with higher incidence of thrombotic events (p = 0.02) in PV |
| Barbui et al. (2017) [52] | International cohort: Italy, Austria, USA | PV | 604 | HTN impacts the incidence of thrombosis in low-risk PV (n = 525). Thrombosis-free survival higher in low-risk PV patients who did not suffer from HTN (IR = 0.85, 95% CI 0.57-1.25 vs. IR = 2.05, 95% CI 1.34-3.14, p = 0.025) Compared to another ET cohort (n = 891), HTN was more prevalent in PV (OR = 1.38, p = 0.022) and BP values positively correlated with hematocrit levels |
| Benevolo et al. (2021) [53] | Italy | PV | 861 | HTN (HR = 1.77, 95% CI 1.03–3.06, p = 0.04) and previous history of thrombosis (HR = 2.10, 95% CI 1.21–3.60, p = 0.01) elevate risk of thrombosis in PV |
| Birgegård et al. (2018) [54] | International cohort: Sweden, Italy, France, UK, USA, Germany, Spain, Switzerland | ET | 3649 | post-hoc multivariate analysis of the Evaluation of Anagrelide Efficacy and Long-term Safety study, long-term research with prospective observational design which recruited high-risk ET cases 34% of ET cases had elevated BP (#1 CVRF in ET) HTN = predictor of major hemorrhages (HR = 1.33, 95% CI 1.04–1.69, p = 0.02) and thrombohemorrhagic complications (HR = 1.69, 95% CI 1.02-2.79, p = 0.04) |
| Cerquozzi et al. (2017) [55] | USA | PV | 587 | 42% of PV cases had HTN rate of arterial and venous thrombotic complications was elevated in subjects with elevated BP (52% vs. 38%, p = 0.004 and 44% vs. 30%, p = 0.009, respectively). Individuals with PV had lower thrombosis-free survival (HR = 1.7, 95% CI 1.1–2.6, p = 0.02) in the univariate but not in the multivariate analysis |
| Cervantes et al. (2006) [56] | Spain | PMF, SMF | 155 | patients with any CVRF (HTN, T2DM, hypercholesterolemia, use of cigarettes) were at an elevated risk for thrombosis (OR = 14.9, 95% CI 2.5–87, p = 0.003) and had lower thrombosis-free survival (~83% vs. 97%, p = 0.02) |
| Navarro et al. (2015) [57] | Brazil | ET | 46 | association between CVRFs and thrombosis (p = 0.01), namely arterial (p = 0.03) and not venous (p > 0.05) thrombotic complications |
| Shih et al. (2002) [58] | Taiwan | ET | 89 | assessment of thrombosis in women with ET and with/without clonal/polyclonal X-chromosome inactivation patterns Thrombosis but not hemorrhage was more common in ET subjects with vs. without HTN (p = 0.002 and p = 0.287, respectively) After adjustment for HTN and age, the risk of thrombotic events was 7 times more elevated in ET individuals with clonal X-chromosome inactivation patterns vs. those without |
| Bucalossi et al. (1996) [59] | Italy | PV, ET | 81 | similar prevalence of HTN in PV and ET with/without thrombosis |
| Landolfi et al. (2007) [60] | International cohort | PV | 1638 | assessment of 1638 subjects from the European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) HTN did not emerge as a predictor for major/arterial/venous thrombosis, AMI, TIA, stroke or peripheral arterial thrombosis |
| Finazzi (2004) [61] | International cohort | PV | 1630 | European Collaboration on Low-Dose Aspirin in Polycythemia Vera (ECLAP) analysis cumulative incidence rate of cardiovascular events (i.e., cardiovascular death and non-fatal thrombotic events) = 5.5 events/100 persons per year Thrombosis = main cause of death Age > 65 years, history of thrombosis = predictors of cardiovascular events smoking, HTN, congestive heart failure = risk factors for thrombosis Platelet counts, myelosuppressive drugs = no association with the risk of cardiovascular events Antiplatelet treatment = only variable associated with lower risk of thrombosis |
| Bazzan et al. (1999) [62] Cortelazzo et al. (1990) [63] |
Italy | ET | 187 100 |
HTN did not impact thrombosis-free survival and life expectancy |
| Jantunen et al. (2001) [64] | Finland | ET | 132 | cigarette use = more common risk factor for thrombosis versus HTN (24.3% versus 20.5%) male gender (p < 0.001) and tobacco consumption (p = 0.01) = risk factors for thrombotic complications, whereas HTN did not (p = 0.34) |
| Barbui et al. (2018) [65] | International cohort | PV, ET, PMF | 597 | HTN = more common occurrence in MPNs who developed ischemic stroke versus those with transient ischemic attacks HTN = prognostic factor in recurrence of stroke (HR = 4.24) |
| Košťál et al. (2020) [66] | Czech Republic | PV, ET, PMF | 1442 | HTN = more common individuals who experienced a stroke or a TIA (~53% vs. ~41%), HTN = risk factor for such complications based on the univariate analysis model (OR = 1.604, 95% CI = 1.219–2.111, p = 0.001) but not on the multivariate logistic models on data with imputed missing values (OR = 1.170, 95% CI 0.845–1.619, p = 0.344 for treated and untreated subjects; OR = 0.918, 95% CI = 0.55–1.534, p = 0.745 for subjects not receiving cytoreductive agents |
| De Stefano et al. (2018) [67] | International cohort | PV, ET, PMF | 597 | assessment of MPNs with history of stroke or TIA similar HTN frequency (stroke vs. TIA = 57% vs. 52%, p > 0.05) HTN = independent risk factor for the recurrence of ischemic stroke in MPNs (HR = 4.24, 95% CI 1.23–14.7) Cytoreduction decreased the risk of stroke re-occurrence by 76% |
| Jiao et al. (2021) [68] | China | ET | 91 | HTN more prevalent (~32% vs. ~4%, p = 0.003) in ET without CVST |
| Robertson et al. (2007) [69] | UK | PV, ET, PMF | 118 | compared to subjects with HTN, individuals diagnosed with MPNs display elevated concentrations of soluble p-selectin (p < 0.001), particularly if they harbor the JAK2V617F mutation (p = 0.006 between JAK2V617F-positive and JAK2V617F-negative cases), and D-dimers (p = 0.03), but similar soluble E-selectin, thrombin–antithrombin complexes, prothrombin fragments or antiphospholipid antibodies soluble p-selectin levels were similar in MPN patients who experienced thrombotic events versus those who did not |
Legend: NS, not specified. For abbreviations, see list of abbreviations.