Epidemiology and pathophysiology of vascular thrombosis in acclimatized lowlanders at high altitude: A prospective longitudinal study.

Background: Previous literature suggests that thrombosis is more common in lowlanders sojourning at high altitude (HA) compared to near-sea-level. Though the pathophysiology is partly understood, little is known of its epidemiology. To elucidate this, an observational prospective longitudinal study was conducted in healthy soldiers sojourning for months at HA. Methods: A total of 960 healthy male subjects were screened in the plains, of which 750 ascended, to altitudes above 15,000ft (4,472m). Clinical examination, haemogram, coagulogram, markers of inflammation and endothelial dysfunction, were studied at three time points during ascent and descent. The diagnosis of thrombosis was confirmed radiologically in all cases where a thrombotic event was suspected clinically. Subjects developing thrombosis at HA were labelled as Index Cases (ICs) and compared to a nested cohort of the healthy subjects (comparison group,(CG)) matched for altitude of stay. Findings: Twelve and three subjects, developed venous (incidence: 5,926/105 person-years) and arterial (incidence: 1,482/105 person-years) thrombosis at HA, respectively. The ICs had enhanced coagulation (FVIIa: p<0.001; FXa: p<0.001) and decreased levels of natural anticoagulants (thrombomodulin, p=0.016; tissue factor pathway inhibitor [TFPI]: p<0.001) and a trend to dampened fibrinolysis (tissue plasminogen activator tPA; p=0.078) compared to CG. ICs also exhibited statistically significant increase in the levels of endothelial dysfunction and inflammation markers (vascular cell adhesion molecule-1[VCAM-1], intercellular adhesion molecule-1 [ICAM-1], vascular endothelial growth factor receptor 3 [VEGFR-3], P-Selectin, CD40 ligand, soluble C-reactive protein and myeloperoxidase: p<0.001). Interpretation: The incidence of thrombosis in healthy subjects at HA was higher than that reported in literature at near sea-level. This was associated with inflammation, endothelial dysfunction, a prothrombotic state and dampened fibrinolysis. Funding: Research grants from the Armed Forces Medical Research Committee, Office of the Director General of Armed Forces Medical Services (DGAFMS) & Defence Research and Development Organization (DRDO), Ministry of Defence, India.

In the search of a 'fitness gene': an analysis of ACTN gene polymorphisms in serving soldiers.

BACKGROUND: Genetic polymorphisms in the exon 15 and exon 16 of the ACTN3 gene are believed to be associated with athletic performance. Paratroopers are some of the fittest soldiers in the Indian Armed Forces. This study was taken up to assess if there was a significant difference in the genetic profile between paratroopers and non-paratroopers. METHOD: Polymerase chain reaction (PCR) followed by restriction length fragment polymorphism (RFLP) was used to analyse the genetic polymorphisms in the exon 15 and 16 of the ACTN3 gene. RESULTS: There was a significant difference between paratroopers and non-paratroopers in the polymorphic loci at codon 15 and 16. CONCLUSIONS: The study suggests that there is a significant difference in the genotype between paratroopers and non-paratroopers. It is likely that the differences in muscle fibres as a result of these genotypic changes confer a 'survival advantage'; people with a homozygous genotype are more likely to pass the harsh probation and qualify for the Parachute Regiment.

Evaluation of nasal obstruction in lowlander males in high altitude.

BACKGROUND: Nasal symptoms are a major problem affecting the quality of life of lowlanders deployed at high altitude. Study was carried out in fresh male inductees inducted in high altitude of 11,500 ft (3500 m) above sea level to evaluate the nasal obstruction using the subjective Nasal obstruction and symptom evaluation (NOSE) score and rhinomanometry during the stay in high altitude. METHODS: A prospective study was carried out in 100 males inducted into high altitude. The subjects were evaluated using the subjective assessment tool, NOSE scale and rhinomanometry on induction and after 2 months. The data were analysed for NOSE scale in the 1st and 2nd visit by test for equality of proportions and the total nasal airway resistance (Pa) has been expressed as mean ± standard deviation and compared across severity of NOSE score using one way ANOVA and between 1st and 2nd visit using paired t test. RESULTS AND CONCLUSIONS: Out of the 100 subjects, 77 came for the 2nd review after 2 months. There was statistically significant worsening in the subjective feeling of nasal obstruction during the stay in high altitude without any significant change in the nasal airway resistance.