Patient’s demographics
Patient’s basic characteristics are summarized in Table 1. Data suggested that frequency distribution was significantly different among all the treatment protocols with regards to age, mostly < 60 years of age (LTN; 85%, N-GITS; 49.5%, LTN + HCT; 71%, N-GITS+LTN + HCT; 51.7%, p < 0.01), family history; mostly had no familial link (LTN; 60%, N-GITS; 76.8%, LTN + HCT; 57%, N-GITS+LTN + HCT; 56.9%, p = 0.01), education; mostly having secondary education (p < 0.01) and physical activity (p < 0.01); more than 44% of the subjects in each treatment arm claimed to have normal physical activity (Table 1). Similarly, majority of the patients on protocols other than LTN were consuming red or white meat 1–2 times a day (N-GITS; 58.9%, LTN + HCT; 80.4%, N-GITS+LTN + HCT; 91.4%, p < 0.01) and had low salt intake (N-GITS; 53.7%, LTN + HCT; 73.8%, N-GITS+LTN + HCT; 86.2%, p < 0.01) (Table 1).
Treatment outcomes and laboratory biochemical values; baseline vs follow ups
Data on treatment outcomes and laboratory biochemical values, baseline (BL) vs follow up, are summarized in Table S1. Data revealed that mean DBP and hemoglobin baseline values were not different among all four cohorts. However, considerable differences existed among cohorts in the mean baseline values of SBP (LTN; 141.87, N-GITS; 156.52, LTN + HCT; 153.73, LTN + N-GITS+HCT; 184.05 mmHg), serum creatinine, serum urea and blood glucose levels (Table S1). When it comes to treatment effects, in last (12 months) follow up, all four therapeutic regimens had significant impact on SBP (LTN: BL; 141.87, 12-months; 123.25, p = 0.001, N-GITS: BL; 156.52, 12-months; 127.63, p = 0.001, LTN + HCT: BL; 153.73, 12-months; 128.54, p = 0.001, LTN + N-GITS + HCT: BL; 184.05, 12-months; 133.88, p = 0.001) and DBP (LTN: BL; 90.12, 12- months; 80.83, p = 0.001, N-GITS: BL; 93.51, 12-months; 81.28, p = 0.001, LTN + HCT: BL; 92.22, 12-months; 82.12, p = 0.001, LTN + N-GITS + HCT: BL; 100.44, 12-months; 84.04, p = 0.001). As for laboratory biochemical values, compared to baseline vs 12-months, mean serum creatinine levels were increased in LTN group only and mean serum urea levels were increased in N-GITS (31.27, p = 0.01), LTN + HCT (30.85, p = 0.001) and LTN + N-GITS+HCT (36.03, p = 0.001) groups. No significant effects of all four regimens were observed on Hb levels (Table S1).
Frequency of co-morbid conditions and therapy related side effects
As shown in Figure S1, diabetes was the most frequent single co-morbid condition (13.6%) followed by anemia (11%), angina (7.7%) and ischemic heart disease (3%). In more than one co-morbid category, diabetes + angina (2.7%) and diabetes + anemia (1.3%) were the notable co-morbid conditions (Fig. S1). As for the side effects, in combination therapy; N-GITS+ LTN + HCT, orthostatic hypertension (15.8%) was most frequently observed side effect followed by edema (6.9%) (Fig. S2). In LTN + HCT group, orthostatic hypertension (8.4%) and headache (8.4%) were reported with similar frequencies. While in mono-therapy, patients on N-GITS experienced edema (5.2%), headache (4.7%) and orthostatic hypertension (3.2%), yet with lower frequencies compared to combination therapy (Fig. S2).
Association of lifestyle patterns with overall hypertensive and high risk population
As shown in Table 2, hypertension was significantly associated with red/white meat intake > 2 times a day (OR; 2, p = 0.01), weight ≥ 65 Kg (OR; 1.63, p = 0.04), vegetables and fruits intake > 2 times a day (OR; 3.34, p = 0.001), salt intake (OR; 2.48, p < 0.01) and physical activity (OR; 2.79, p = 0.001). When adjusted for covariates, only salt intake, vegetables and fruit intake, and physical activity demonstrated significant associations with hypertension (Table 2).
When patients were segregated into low and high risk groups, as described in method section, forest plot revealed that high risk women were more likely to have normal salt intake (OR; 2.48, ref; low intake), meat intake > 2 times (OR; 2.02, ref; 1–2 times), vegetables and fruits intake > 2 times (OR; 3.43, ref; 1–2 times) and body weight ≥ 65Kg (OR;1.54, ref; <65Kg) compared to low risk subjects, despite normal physical activity and fat intake (OR; 1.54, ref; low intake) (Fig. 2).
Forest Plot Showing Odd Ratios of Factors Associated with Hypertension in Women with Co-morbidities
Changes in outcome measures at each follow up in hypertensive women
To examine the changes in outcome measures at each follow up in comparison to baseline values, we fitted models with second-order interaction between therapy and time in order to investigate the changes of the primary outcomes over time (Table 3). The mean changes reported in Table 3 are within various anti-hypertensive therapies relative to baseline, adjusted for socio-demographic factors. All treatment protocols, LTN, N-GITS, LTN + HCT and N-GITS + LTN + HCT demonstrated significant reduction in SBP starting at 3 months of follow up till 12 months, though maximum reduction was observed in N-GITS + LTN + HCT therapy group (β; − 50.17, p < 0.001) followed by N-GITS (β; − 28.89, p < 0.001), a similar trend was observed for DBP – N-GITS + LTN + HCT therapy group (β; − 16.55, p < 0.001) followed by N-GITS (β; − 12.21, p < 0.001) (Table 3). Compared to baseline laboratory biochemical values, at final follow up, 12 months, BSR levels exhibited maximum reduction in N-GITS (β; − 25.29, p < 0.001) and N-GITS + LTN + HCT therapy (β; − 24.93, p < 0.001) groups, while urea levels were increased in N-GITS + LTN + HCT (β; 3.47, p < 0.001) and LTN + HCT (β; 5.16, p < 0.001) groups (Table 3). Interestingly, only N-GITS treatment resulted in modest changes in blood urea and creatinine levels, which started to appear in 3rd follow up (Table 3).
Changes in outcome measures, low vs high risk hypertensive women
Table 4 showed the changes in outcome measures, i-e., SBP, DBP, urea, BSR and creatinine within and between low (LR) and high risk (HR) hypertensive women, adjusted for treatment effects, at each follow up. In low and high risk groups, compared to baseline, we observed significant reduction in SBP (at 12 months: LR; β; − 17.92, p < 0.001, HR; − 19.48, p < 0.001) and DBP (at 12 months: LR; β; − 9.49, p < 0.001, HR; − 10.12, p < 0.001) at each follow up, which became maximum at final follow up (12 months). In both low and high risk groups, compared to baseline, changes in urea and creatinine were observed after 2nd and 3rd follow ups (Table 4). But regarding changes between the groups, low vs high risk, only SBP (β; − 1.55, p = 0.03) demonstrated a significant change at final follow up (Table 4).
