Abstract
Background
Cardiovascular disease is the leading cause of death globally, with approximately 80% of these deaths occurring in low- and middle-income countries. Sex differences in cardiovascular disease are well described in high-income countries but limited in low- and middle-income countries.
Objectives
This study sought to evaluate the sex differences in clinical presentation, cardiovascular risk profile, diagnosis, treatment, and outcomes among patients in the Kenya Heart Registry.
Methods
Data were prospectively collected from 3 tertiary hospitals, including patients with heart failure, acute coronary syndrome, venous thromboembolism, and atrial fibrillation. Primary outcomes were in-hospital and 6-month mortality, as well as sex-specific differences in clinical presentation, cardiovascular risk factors, diagnosis, and treatment.
Results
Among 1,687 participants, 51.3% were women. Of these, 1,241 were admitted, while 446 were managed as outpatients. Women were younger (50.9 vs 54.2 years; P < 0.001), had lower monthly income, higher left ventricular ejection fraction, higher rates of heart failure with preserved ejection fraction, venous thromboembolism, and atrial fibrillation, and lower rates of acute coronary syndrome than men. No sex difference was observed in diagnostics or treatment or adherence to guideline-directed therapies. In-hospital and 6-month all-cause mortality were 7.4% and 14.7%, respectively, and were similar by sex (women 8.0% and 14.8% vs men 6.9% and 14.5%; P = 0.449 and P = 0.881, respectively).
Conclusions
Significant sex differences exist in clinical profiles, but management and outcomes are similar. Scaling up evidence-based interventions is urgently needed to reduce the high mortality in this population.
Key words: cardiac rehabilitation, cardiovascular disease, heart failure, registry data, sex differences, sub-Saharan Africa
Central Illustration
Cardiovascular disease (CVD) is the leading cause of death globally, with approximately 80% of deaths occurring in low- and middle-income countries (LMICs).1 Evidence mainly from high-income countries shows sex-related differences in the CVD prevalence, risk factors, clinical presentation, treatment, and outcomes.2,3 According to the Global Burden of Disease Study, females have higher rates of hypertensive heart disease, rheumatic heart disease, and nonvalvular heart disease. In contrast, males have more cardiomyopathies and ischemic heart disease.4 Although males have higher age-adjusted death rates than females, some countries in sub-Saharan Africa report higher mortality rates in females.5
Biological, behavioral, and sociocultural factors influence sex differences in CVDs.3 The X chromosome plays a role in inflammation and the development of autoimmune conditions, which are more common in females and increase the risk of CVDs. Hormonal changes, such as a decrease in estrogen after menopause, further elevate the risk.3 Other female-specific risk factors include pre-eclampsia, polycystic ovarian syndrome, and gestational diabetes.6 Psychological and social factors such as stress, anxiety, depression, and low education levels are more prevalent in females, and also raise CVD risk.3
Sex-related disparities in the prevalence of cardiovascular risk factors such as obesity, hypertension, and type 2 diabetes have been reported in studies from LMICs. Women in LMICs are approximately 3 times more likely to be obese than men, with this disparity being more pronounced in sub-Saharan Africa. Differences in hypertension and type 2 diabetes are less marked, with men exhibiting a higher risk of hypertension, while women have a greater risk of developing type 2 diabetes.7
The clinical presentation, diagnosis, treatment, and outcomes of CVDs also differ between the sexes.3 Women with coronary artery disease often present with atypical symptoms, which can lead to underdiagnosis and undertreatment. Males typically present with more calcified plaques and extensive obstruction.3 Women are less likely to undergo angiography, revascularization procedures, or be referred to cardiac rehabilitation (CR) after ST-segment elevation myocardial infarction (STEMI), which contributes to their poorer prognosis.3,8 A recent meta-analysis on sex differences in long-term heart failure (HF) prognosis found that females had a more favorable overall outcome, with lower risks of cardiovascular mortality, hospitalization for HF, and all-cause mortality, despite lower rates of guideline-directed medical therapy use. In addition, more females present with HF with preserved ejection fraction (HFpEF).3,9
The objective of this study was to evaluate the sex differences in clinical characteristics, cardiovascular risk factors, diagnosis, treatment, and clinical outcomes among participants enrolled in the Kenya Heart Registry.
Methodology
Study design
These data were prospectively collected from 3 tertiary referral hospitals as part of the Kenya Heart Registry, a longitudinal survey of patients with HF, acute coronary syndrome (ACS), venous thromboembolism (VTE), and atrial fibrillation (AF) recruited from both inpatient and outpatient settings between 2019 and 2023.
Study population
The 3 hospitals are Kenyatta National Hospital (public, Nairobi) which primarily serves central and eastern Kenya; Aga Khan University Hospital (private, Nairobi) which draws patients nationally through its private referral network; and the Moi Teaching and Referral Hospital (public, Eldoret), which serves western and parts of northern Kenya. Together, these institutions represent both urban and rural populations across the public and private health sectors.
The study recruited participants enrolled in the registry with a diagnosis of HF, ACS, VTE, and AF. The following definitions were used to confirm the above diagnoses:
Acute coronary syndrome
Must fulfill 2 of 3 criteria:
-
1)
Chest pains or equivalent symptoms
-
2)
Abnormal electrocardiogram (ECG) with ST-segment elevation (STEMI), ST-segment depression, dynamic ST-T changes
-
3)
Raised cardiac troponin
Heart failure
HF will be diagnosed as follows:
-
1)
Symptoms or signs of HF PLUS objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of left ventricular (LV) diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides (elevated N-terminal pro-B-type natriuretic peptide of >300 pg/mL, B-type natriuretic peptide >100 pg/mL. If in AF BNP >600 pg/mL; NT-proBNP >900 pg/mL)
-
2)
Hemodynamically significant (severe) valvular heart disease
Atrial fibrillation
This will be diagnosed based on the criteria below:
-
1)
Any ECG with AF that is not related to recent <2 weeks of cardiac surgery or <48 hours of ACS
-
2)
Holter monitor with AF
-
3)
Loop recorder with AF >30 seconds
-
4)
Cardiac pacemaker/implantable cardioverter-defibrillator or cardiac resynchronization therapy with AF >30 seconds
Venous thromboembolism
Diagnostic criteria:
-
1)
Positive Doppler ultrasound showing thrombus in the extremities
-
2)
Computed tomography (CT) scan or magnetic resonance imaging showing thrombus in the pulmonary veins and branches, other central vein thrombosis, mesenteric and portal vein thrombosis, and cerebral venous sinus thrombosis
Patients were enrolled in the registry using consecutive sampling. During routine clinical care, the primary physician identified all patients who met the eligibility criteria within the study period. The physician then worked with a trained research nurse to verify the diagnosis and eligibility based on clinical records. Once eligibility was confirmed, the research nurse provided study information and obtained written informed consent for inclusion in the registry.
Data management
Recruited participants were assigned a unique code, which was used to track the patient throughout the study. A manual case report form was used to collect data during admission, after which the data were entered into a web-based database (RedCap).
Data were collected on demographic characteristics, clinical presentation, medical history, comorbidities, cardiovascular risk factors, symptoms, cause of HF, investigations (including blood and imaging), treatment (medical, surgical, interventions, and rehabilitation), cost of treatment, and outcomes (in-hospital mortality). At 6 months, a telephone interview was conducted to collect data on vital status, rehospitalization, symptoms, medications, and participation in a CR program. Sex was self-reported. Diagnosis at 6-month follow-up was based on the initial diagnosis at recruitment.
Statistical analysis
Descriptive analysis was performed for the overall sample and separately comparing males and females. Summary statistics were presented as means and SDs for continuous data and frequencies and percentages for categorical data. Univariate analyses were performed using chi-square or Fisher exact test for categorical data and Student’s t-test or Kruskal-Wallis test for continuous data to identify differences between sexes. Furthermore, to identify independent associations with sex and mortality, multivariate logistic regression was used after adjusting for sociodemographic characteristics (age, race, income, and body mass index [BMI]). Analyses were conducted using complete case data; no imputation for missing values was performed. All analyses were performed using SPSS version 20 (IBM Corp).
Ethical considerations
Patients gave informed consent after receiving information about the study. The study received ethical approval from the Aga Khan University Hospital Institutional Scientific and Ethics Review Committee, Moi Teaching and Referral Hospital/Moi University College of Health Sciences–Institutional Scientific and Ethical Review Committee, Kenyatta National Hospital-University of Nairobi Ethics and Research Committee, and the National Commission for Science, Technology, and Innovation, a body that regulates all national research projects.
Results
A total of 1,687 patients were included in the Kenya Heart Registry, with 866 (51.3%) females. Of these, 1,241 were admitted, while 446 were managed as outpatients. There were 794 (47.1%) with HF, 420 (24.9%) with VTE, 247 (14.6%) with ACS, and 226 (13.4%) with AF (Table 1). There was a significant sex difference in the distribution of CVDs, with more males having ACS (23.4% vs 6.4%) and more females having VTE (32% vs 17%), HF (47.5% vs 46.7%), and AF (14.2% vs 12.5%). The participants’ mean age was 52.5 years. Females were younger than males (mean age 50.9 ± 18.9 years vs 54.2 ± 17.4 years; P < 0.001) (Table 1). The majority (91.9%) of participants were of Black African origin, with a higher proportion among males compared to females (96.9% vs 86.7%). Females were more likely than males to be of non-African ethnic background (P < 0.001). Females had a lower monthly income, with more females earning <10,000 (76.3% vs 53.1%), and more males earning >100,000 (22.9% vs 5.8%) (P < 0.001) (Table 1). Of the 1,687 patients enrolled, 1,526 were available for the 6-month follow-up, while 161 (10%) were not available.
Table 1.
Demographic and Cardiovascular Risk Profile of Study Participants
| Overall (N = 1,687) | Female (n = 866) | Male (n = 821) | P Value | |
|---|---|---|---|---|
| Diagnosis at presentation (hospital admission or outpatient visit) | ||||
| Heart failure | 794 (47.1%) | 411 (47.5%) | 383 (46.7%) | <0.001 |
| Acute coronary syndrome | 247 (14.6%) | 55 (6.4%) | 192 (23.4%) | |
| Atrial fibrillation | 226 (13.4%) | 123 (14.2%) | 103 (12.5%) | |
| Venous thromboembolism | 420 (24.9) | 277 (32.0%) | 143 (17.4%) | |
| Age, y (mean) (n = 1,670) | 52.5 [18.3] | 50.9 [18.9] | 54.2 [17.4] | <0.001 |
| Ethnicity (%) (n = 1,677) | ||||
| African | 1,542 (91.9%) | 837 (96.9%) | 705 (86.7%) | <0.001 |
| Asian | 72 (4.3%) | 17 (2.0%) | 55 (6.8%) | |
| Caucasian | 39 (2.3%) | 8 (0.9%) | 31 (3.8%) | |
| Other | 24 (1.4%) | 2 (0.2%) | 22 (2.7%) | |
| Income (monthly, Ksh) (n = 1,072) | ||||
| <10,000 | 689 (64.3%) | 395 (76.3%) | 294 (53.1%) | <0.001 |
| 10,000–50,000 | 136 (12.7%) | 53 (10.2%) | 83 (15.0%) | |
| 51,000–100,000 | 90 (8.4%) | 40 (7.7%) | 50 (9.0%) | |
| >100,000 | 157 (14.6%) | 30 (5.8%) | 127 (22.9%) | |
| BMI categories (%) (n = 1,655) | ||||
| Underweight <18.5 kg/m2 | 97 (5.9%) | 49 (5.8%) | 48 (5.9%) | 0.088 |
| Healthy 18.5–24.9 kg/m2 | 717 (43.3%) | 357 (42.1%) | 360 (44.6%) | |
| Overweight 25.0–29.9 kg/m2 | 512 (30.9%) | 252 (29.8%) | 260 (32.2%) | |
| Obese ≥30.0 kg/m2 | 329 (19.9%) | 189 (22.3%) | 140 (17.3%) | |
| Smoking status (%) (n = 1,683) | ||||
| Current | 83 (4.9%) | 12 (1.4%) | 71 (8.7%) | <0.001 |
| Former | 243 (14.4%) | 50 (5.8%) | 193 (23.6%) | |
| Never | 1,357 (80.6%) | 803 (92.8%) | 554 (67.7%) | |
| Alcohol use (%) (n = 1,011) | ||||
| Current | 187 (18.5%) | 50 (9.4%) | 137 (28.5%) | <0.001 |
| Former | 65 (6.4%) | 10 (1.9%) | 55 (11.5%) | |
| Never | 759 (75.1%) | 471 (88.7%) | 288 (60.0%) | |
| Hypertension (%) (Yes, n = 1,266) | 528 (41.7%) | 261 (44.4%) | 267 (39.4%) | 0.077 |
| Diabetes mellitus (%) (Yes, n = 1,267) | 250 (19.7%) | 101 (17.1%) | 149 (22.0%) | 0.034 |
| HIV positive (%) (n = 657) | 35 (5.3%) | 15 (5.8%) | 20 (5.0%) | 0.724 |
| Cancer (%) (Yes, n = 1,018) | 26 (2.6%) | 14 (2.6%) | 12 (2.5%) | 1.000 |
| In-hospital mortality (%) (dead, n = 1,240) | 92 (7.4%) | 47 (8.0%) | 45 (6.9%) | 0.449 |
Values are n (%).
BMI = body mass index.
Missing data were as follows: income (615, 36%), alcohol use (676, 40%), hypertension status (421, 30%), diabetic status (420, 25%), HIV status (1,030, 61%), and a history of cancer (669, 40%).
Cardiovascular risk factors
More than half of the participants (50.8%) were classified as overweight or obese with no significant difference between males and females. Other common cardiovascular risk factors included hypertension (41.7%), diabetes mellitus (19.7%), alcohol use (24.9%), and smoking (19.3%). Males were more likely to smoke, take alcohol, and have diabetes (Table 1).
Diagnosis and clinical characteristics
Of all patients recruited, the majority (794, 47.1%) presented with HF, 420 (24.9%) with VTE, 247 (14.6%) with ACS, and 226 (13.4%) with AF. Below, we describe the sex differences in demographics, clinical characteristics, risk factors, diagnostic tests, treatment modalities, and outcomes for patients presenting with each of these conditions.
Heart failure
The mean age at presentation was 52 ± 18.4 years, with no significant difference between males and females. The majority of the participants had HF with reduced ejection fraction (82.6%), but females were more likely than males to have HFpEF (22.3% vs 12.0%; P < 0.001). Dilated cardiomyopathy (33.8%), hypertensive heart disease (25.6%), and rheumatic heart disease (12.7%) were the most common etiologies of HF.
More females were diagnosed with hypertensive heart disease (29.0% vs 21.9%; P = 0.029). In contrast, more males were diagnosed with alcoholic cardiomyopathy (8.9% vs 0.2%; P < 0.001). The proportion of females with peripartum cardiomyopathy as the etiology of HF was 8.8%. Other HF etiologies did not differ by sex.
There was no significant difference in NYHA functional class at presentation between males and females (P = 0.052). However, females were more severely limited in their activities of daily living than males (P = 0.008). Data on NYHA were missing for 153 (19%) of patients.
These findings are summarized in Table 2 below.
Table 2.
Diagnosis and Clinical Characteristics of Patients With Heart Failure
| Overall (N = 794) | Female (n = 411) | Male (n = 383) | P Value | |
|---|---|---|---|---|
| Age (mean, SD) | 52.0 (18.4) | 51.7 (18.5) | 52.3 (18.3) | 0.600 |
| Heart failure type (n = 749) | ||||
| HFrEF | 619 (82.6%) | 304 (77.7%) | 315 (88.0%) | <0.001 |
| HFpEF | 130 (17.4%) | 87 (22.3%) | 43 (12.0%) | |
| Heart failure etiology | ||||
| Hypertension | 203 (25.6%) | 119 (29.0%) | 84 (21.9%) | 0.029 |
| Dilated cardiomyopathy | 268 (33.8%) | 126 (30.7%) | 142 (37.1%) | 0.066 |
| Rheumatic heart disease | 101 (12.7%) | 58 (14.1%) | 43 (11.2%) | 0.266 |
| Alcoholic cardiomyopathy | 35 (4.4%) | 1 (0.2%) | 34 (8.9%) | <0.001 |
| Ischemic heart disease | 32 (4.2%) | 12 (3.0%) | 20 (5.5%) | 0.089 |
| Peripartum cardiomyopathy | 36 (4.5%) | 36 (8.8%) | 0 (0.0%) | <0.001 |
| Pulmonary hypertension | 9 (1.1%) | 5 (1.2%) | 4 (1.0%) | 1.000 |
| Other | 63 (7.9%) | 30 (7.3%) | 33 (8.6%) | 0.579 |
| Unknown | 44 (5.5%) | 24 (5.8%) | 20 (5.2%) | 0.822 |
| LV systolic function (%) (n = 786) | ||||
| <40 | 597 (76.0%) | 288 (70.8%) | 309 (81.5%) | 0.001 |
| 40-50 | 102 (13.0%) | 59 (14.5%) | 43 (11.3%) | |
| >50 | 87 (11.1%) | 60 (14.7%) | 27 (7.1%) | |
| LA size by LAVi (mL/m2) (N = 791) | ||||
| Normal | 123 (15.5%) | 71 (17.3%) | 52 (13.6%) | 0.543 |
| Mild LAE | 307 (38.8%) | 157 (38.3%) | 150 (39.4%) | |
| Moderate LAE | 213 (26.9%) | 106 (25.9%) | 107 (28.1%) | |
| Severe LAE | 148 (18.7%) | 76 (18.5%) | 72 (18.9%) | |
| Blood pressure (BP) | ||||
| Systolic BP (mean, SD) | 125.8 (25.7) | 126.2 (24.8) | 125.5 (26.6) | 0.580 |
| Diastolic BP (mean, SD) | 82.5 (19.2) | 83.0 (17.9) | 82.0 (20.5) | 0.250 |
| NYHA functional class at presentation (n = 641) | ||||
| I | 7 (1.1%) | 1 (0.3%) | 6 (1.9%) | 0.052 |
| II | 238 (37.1%) | 132 (39.9%) | 106 (34.2%) | |
| III | 281 (43.8%) | 134 (40.5%) | 147 (47.4%) | |
| IV | 115 (17.9%) | 64 (19.3%) | 51 (16.5%) | |
| Activities of daily living (n = 791) | ||||
| No limitation | 50 (6.3%) | 16 (3.9%) | 34 (8.9%) | 0.008 |
| Mild limitation | 507 (64.1%) | 261 (64.0%) | 246 (64.2%) | |
| Severe limitation | 234 (29.6%) | 131 (32.1%) | 103 (26.9%) | |
| Depressive symptoms at presentation | ||||
| None | 285 (35.9%) | 152 (37.0%) | 133 (34.7%) | 0.677 |
| Mild | 263 (33.1%) | 137 (33.3%) | 126 (32.9%) | |
| Moderate | 233 (29.3%) | 114 (27.7%) | 119 (31.1%) | |
| Severe | 13 (1.6%) | 8 (1.9%) | 5 (1.3%) |
HFpEF = heart failure with preserved ejection fraction; HFrEF = heart failure with reduced ejection fraction; LA = left atrial; LAE = left atrial enlargement; LV = left ventricular; LAVi = left atrial volume index.
Acute coronary syndrome
In this cohort, the mean age at presentation was higher in females than in males (62.1 years vs 58.2 years; P = 0.047). Males were more likely to be current or former smokers (35.9% vs 11.0%; P = 0.002).
There was no significant difference between males and females in the use of statin or antiplatelet therapy before admission for ACS. Data on medication used before admission were missing in 181 (73%) of patients.
Most (85%) participants underwent invasive coronary assessment through coronary angiography. There was no statistical difference between males and females referred for this procedure. Regarding coronary revascularization, 186 (75.2%) underwent percutaneous coronary intervention (PCI) with no statistically significant difference between the sexes. STEMI presentations accounted for 68% of the entire cohort, with no significant sex difference in the type of ACS (Table 3).
Table 3.
Diagnosis and Clinical Characteristics of Patients With Acute Coronary Syndrome
| Overall (N = 247) | Female (n = 55) | Male (n = 192) | P Value | |
|---|---|---|---|---|
| Age (mean, SD) | 59.1 (12.9%) | 62.1 (14.2) | 58.2 (12.4%) | 0.047 |
| History (n = 91) | ||||
| History of previous MI | 29 (11.7%) | 6 (10.9%) | 23 (12.0%) | 1.000 |
| Prior angina | 54 (21.9%) | 11 (20.0%) | 43 (22.4%) | 0.853 |
| History of stroke | 7 (2.8%) | 2 (3.6%) | 5 (2.6%) | 0.655 |
| History of PAD | 1 (0.4%) | 0 (0.0%) | 1 (0.5%) | 1.000 |
| Risk factors | ||||
| Smoking | ||||
| Current | 29 (11.7%) | 3 (5.5%) | 26 (13.5%) | 0.002 |
| Former | 46 (18.6%) | 3 (5.5%) | 43 (22.4%) | |
| Never | 172 (69.6%) | 49 (89.1%) | 123 (64.1%) | |
| Diabetes mellitus | 103 (41.7%) | 24 (43.6%) | 79 (41.1%) | 0.758 |
| Hypertension | 129 (52.2%) | 32 (58.2%) | 97 (50.5%) | 0.360 |
| Dyslipidemia | 60 (26.5%) | 10 (21.3%) | 50 (27.9%) | 0.463 |
| Coronary angiography (yes) | 210 (85.0%) | 45 (81.8%) | 165 (85.9%) | 0.520 |
| Percutaneous coronary intervention (yes) | 186 (75.3%) | 38 (69.1%) | 148 (77.1%) | 0.287 |
| Medication on admission (n = 66) | ||||
| Antiplatelet | 22 (9.0%) | 6 (10.9%) | 16 (8.4%) | 0.764 |
| Statin | 44 (18.2%) | 8 (14.8%) | 36 (19.1%) | 0.583 |
| Killip class (n = 130) | ||||
| I | 62 (47.7%) | 10 (38.5%) | 52 (50.0%) | 0.600 |
| II | 43 (33.1%) | 11 (42.3%) | 32 (30.8%) | |
| III | 24 (18.5%) | 5 (19.2%) | 19 (18.3%) | |
| IV | 1 (0.8%) | 0 (0.0%) | 1 (1.0%) | |
| Electrocardiogram ST-segment changes | ||||
| Normal | 12 (4.9%) | 5 (9.1%) | 7 (3.6%) | 0.463 |
| ST-segment elevation | 176 (71.3%) | 37 (67.3%) | 139 (72.4%) | |
| ST-segment depression | 22 (8.9%) | 6 (10.9%) | 16 (8.3%) | |
| Pathological T-inversion (in absence of ST-segment elevation) | 28 (11.3%) | 6 (10.9%) | 22 (11.5%) | |
| Other | 9 (3.6%) | 1 (1.8%) | 8 (4.2%) | |
| Troponin | ||||
| HS troponin I, median [IQR] | 1915.7 [141.9, 17,617.5] | 1,211.1 [148.0, 22.057.5] | 2096.0 [141.9, 16,654.9] | 0.829 |
| HS troponin T, median [IQR] | 454.2 [81.4, 1,316.0] | 802.5 [28.4, 1,123.0] | 237.0 [141.0, 1,339.0] | 0.900 |
| Troponin I elevated within 48 h of admission (n = 60) (Yes) | 54 (90.0%) | 13 (81.3%) | 41 (93.2%) | 0.328 |
| Troponin T elevated within 48 h of admission (n = 50) (Yes) | 35 (70.0%) | 6 (66.7%) | 29 (70.7%) | 1.000 |
| Working diagnosis | ||||
| STEMI/LBBB | 168 (68.0%) | 36 (65.5%) | 132 (68.8%) | 0.271 |
| NSEMI | 70 (28.3%) | 15 (27.3%) | 55 (28.6%) | |
| Unstable angina | 9 (3.6%) | 4 (7.3%) | 5 (2.6%) |
LBBB = left bundle branch block; MI = myocardial Infarction; NSTEMI = non–ST-segment elevation myocardial infarction; PAD = peripheral arterial disease; STEMI = ST-segment elevation myocardial infarction.
Atrial fibrillation
Almost all (99.1%) participants were diagnosed with AF using a 12-lead ECG with no sex difference. More females than males had permanent AF (24% vs 12.9%), whereas more males than females presented with paroxysmal AF (26.7% vs 16.5%), a statistically significant difference (P = 0.041) (Table 4).
Table 4.
Diagnosis and Clinical Characteristics of Patients With Atrial Fibrillation
| Overall (N = 226) | Female (n = 123) | Male (n = 103) | P Value | |
|---|---|---|---|---|
| Age, mean [SD] | 58.3 [20.7] | 58.2 [21.3] | 58.4 [20.0] | 0.899 |
| Diagnosis | ||||
| ECG | 224 (99.1%) | 122 (99.2%) | 102 (99.0%) | 1.000 |
| PPM/ICD/CRT | 2 (0.9%) | 1 (0.8%) | 1 (1.0%) | |
| Type (n = 222) | ||||
| Paroxysmal | 47 (21.2%) | 20 (16.5%) | 27 (26.7%) | 0.041 |
| Persistent | 133 (59.9%) | 72 (59.5%) | 61 (60.4%) | |
| Permanent | 42 (18.9%) | 29 (24.0%) | 13 (12.9%) | |
| History of stroke/TIA | 7 (3.1%) | 2 (1.6%) | 5 (4.9%) | 0.250 |
| Family history of AF | 8 (3.5%) | 6 (4.9%) | 2 (1.9%) | 0.296 |
AF = atrial fibrillation; CRT = cardiac resynchronization therapy; ECG = electrocardiogram; ICD = implantable cardioverter-defibrillator; PPM = permanent pacemaker; TIA = transient ischemic attack.
Venous thromboembolism
The mean age at VTE presentation was younger in females compared to males (44.2 vs 51.1 years; P < 0.001). Additionally, more females than males presented with deep venous thrombosis (58.5% vs 44.8%), while more males than females presented with pulmonary embolism (46.9% vs 34.3%; P = 0.034). Only 7.1% of participants were diagnosed with both deep venous thrombosis and pulmonary embolism in the same presentation, with no statistical difference by sex.
Regarding the risk factors, males were more likely to report a family history of VTE (9.1% vs 0.6%; P = 0.005), renal insufficiency (20.0% vs 4.5%; P = 0.001), and a history of long-haul travel (11.5% vs 3.8%; P = 0.32). In most patients (47.6%), no identifiable VTE provoking risk factor was found, and this was more common in males than in females (61.5% vs 43.3%; P < 0.001). Surgery was more frequently reported as a provoking risk factor in females than males (20.3% vs 6.9%; P = 0.011). The most commonly used diagnostic confirmatory tests were compression ultrasound (57.1%) and CT pulmonary angiography (49.0%) (Table 5).
Table 5.
Diagnosis and Clinical Characteristics of Patients With Venous Thromboembolism
| Overall (N = 420) | Female (n = 277) | Male (n = 143) | P Value | |
|---|---|---|---|---|
| Age mean [SD] | 46.6 [17.0] | 44.2 [16.5] | 51.1 [17.2] | <0.001 |
| VTE classification | ||||
| DVT | 226 (53.8%) | 162 (58.5%) | 64 (44.8%) | 0.034 |
| PE | 162 (38.6%) | 95 (34.3%) | 67 (46.9%) | |
| DVT and PE | 30 (7.1%) | 19 (6.9%) | 11 (7.7%) | |
| Other | 2 (0.5%) | 1 (0.4%) | 1 (0.7%) | |
| PE (n = 192) | ||||
| Main PA | 81 (42.2%) | 49 (43.0%) | 32 (41.0%) | 0.961 |
| Lobar PA branch | 31 (16.1%) | 18 (15.8%) | 13 (16.7%) | |
| Segmental PA branch | 80 (41.7%) | 47 (41.2%) | 33 (42.3%) | |
| Risk factors | ||||
| None | 208 (49.5%) | 120 (43.3%) | 88 (61.5%) | <0.001 |
| Prior VTE | 30 (14.2%) | 19 (21.1%) | 11 (20.0%) | 0.222 |
| Family history VTE (1st degree) | 6 (2.8%) | 1 (0.6%) | 5 (9.1%) | 0.005 |
| Cancer | 63 (29.7%) | 44 (28.0%) | 19 (34.5%) | 0.460 |
| Immobilization (>4 days) | 38 (17.9%) | 23 (14.6%) | 15 (27.3%) | 0.058 |
| Chronic heart failure | 6 (2.8%) | 5 (3.2%) | 1 (1.8%) | 1.000 |
| Renal insufficiency | 18 (8.5%) | 7 (4.5%) | 11 (20.0%) | 0.001 |
| Varicose veins | 4 (1.9%) | 2 (1.3%) | 2 (3.6%) | 0.277 |
| Provoking risk factor | ||||
| None | 200 (47.6%) | 144 (52.0%) | 56 (39.2%) | 0.017 |
| Surgery | 33 (15.0%) | 27 (20.3%) | 6 (6.9%) | 0.011 |
| Trauma to lower limb | 24 (10.9%) | 10 (7.5%) | 14 (16.1%) | 0.076 |
| Acute medical illness | 85 (38.6%) | 50 (37.6%) | 35 (40.2%) | 0.802 |
| Hospitalization >2 weeks | 17 (7.7%) | 6 (4.5%) | 11 (12.6%) | 0.051 |
| Long haul travel | 15 (6.8%) | 5 (3.8) | 10 (11.5%) | 0.032 |
| Active cancer | 59 (26.8%) | 39 (29.3%) | 20 (23.0%) | 0.378 |
| Recent bleeding or anemia <9 g/dL | 19 (8.6%) | 15 (11.3%) | 4 (4.6%) | 0.093 |
| Diagnostic confirmatory test | ||||
| Ventilatory perfusion scan | 2 (0.5%) | 2 (0.7%) | 0 (0.0%) | 0.550 |
| CTPA | 206 (49.0%) | 133 (48.0%) | 73 (51.0%) | 0.627 |
| Compression ultrasound | 240 (57.1%) | 170 (61.4%) | 70 (49.0%) | 0.020 |
| Echocardiography | 11 (2.6%) | 6 (2.2%) | 5 (3.55) | 0.521 |
| Contrast venography | 3 (0.7%) | 2 (0.7%) | 1 (0,7%) | 1.000 |
| D-dimer positive | 43 (10.2%) | 32 (11.6%) | 11 (7.7%) | 0.286 |
| MRI | 1 (0.2%) | 1 (0.4%) | 0 (0.0%) | 1.000 |
CTPA = computed tomography pulmonary angiography; DVT = deep venous thrombosis; MRI = magnetic resonance imaging; PA = pulmonary artery, PE = pulmonary embolism; VTE = venous thromboembolism.
Treatment outcomes at discharge and 6 months
Heart failure
In the HF cohort, 76.3% had a NYHA classification of I or II at 6 months compared to 38.2% at admission, with no sex differences noted. In addition, 86.4% reported mild or no limitation at 6 months compared to 70.4% at admission, with no difference between the sexes. The proportion of HF patients with depressive symptoms at 6 months was lower than that during the index admission (12.8% vs 64.1%) with no statistically significant sex difference.
With regard to patients with HF on guideline-directed medical therapy at 6 months, 56.1% were on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), 62.8% on a beta-blocker, 45.3% on a mineralocorticoid receptor agonist (MRA), and 74.3% on a diuretic. There were no sex differences in the proportion of patients on these medications. Only 7 (1.2%) participants (5 males and 2 females) participated in CR with no sex difference (Table 6).
Table 6.
Treatment and Clinical Outcomes at 6 Months by Sex
| Overall | Female | Male | P Value | |
|---|---|---|---|---|
| Heart failure | ||||
| Patients with data at 6 months follow-up | 716 | 379 (52.9%) | 337 (47.1%) | |
| Admitted/readmitted (n = 670) | 78 (11.6%) | 39 (10.9%) | 39 (12.5%) | 0.547 |
| Heart failure treatment | ||||
| ACEI | 285 (44.4%) | 147 (43.9%) | 138 (45.0%) | 0.812 |
| ARB | 75 (11.7%) | 40 (11.9%) | 35 (11.4%) | 0.903 |
| Beta-blocker | 406 (62.8%) | 210 (62.3%) | 196 (63.4%) | 0.807 |
| MRA | 292 (45.3%) | 154 (45.7%) | 138 (44.8%) | 0.874 |
| Diuretic | 478 (74.3%) | 256 (76.0%) | 222 (72.5%) | 0.366 |
| Digoxin | 120 (18.8%) | 64 (19.2%) | 56 (18.4%) | 0.84 |
| DOACs | 88 (13.8%) | 47 (14.1%) | 41 (13.4%) | 0.819 |
| Statins | 95 (15.0%) | 41 (12.3%) | 54 (17.9%) | 0.058 |
| Devices (n = 639) | ||||
| Dual chamber/ICD/CRT | 8 (1.3%) | 3 (0.9%) | 5 (1.7%) | 0.487 |
| Participated in CR (n = 581) | 7 (1.2%) | 2 (0.7%) | 5 (1.3%) | 0.468 |
| NYHA functional class (n = 342) | ||||
| I | 51 (14.9%) | 26 (14.0%) | 25 (16.0%) | 0.742 |
| II | 210 (61.4%) | 118 (63.4%) | 92 (59.0%) | |
| III | 75 (21.9%) | 38 (20.4%) | 37 (23.7%) | |
| IV | 6 (1.8%) | 4 (2.2%) | 2 (1.3%) | |
| Activities of daily living (n = 592) | ||||
| No limitation | 198 (33.4%) | 95 (30.4%) | 103 (36.8%) | 0.262 |
| Mild limitation | 314 (53.0%) | 172 (55.1%) | 142 (50.7%) | |
| Significant limitation | 80 (13.5%) | 45 (14.4%) | 35 (12.5%) | |
| Depressive symptoms (n = 595) | ||||
| None | 519 (87.2%) | 273 (87.2%) | 246 (87.2%) | 0.626 |
| Mild | 67 (11.3%) | 36 (11.5%) | 31 (11.0%) | |
| Moderate | 7 (1.2%) | 4 (1.3%) | 3 (1.1%) | |
| Severe | 2 (0.3%) | 0 (0.0%) | 2 (0.7%) | |
| Acute coronary syndrome | ||||
| Patients with data at 6 months follow-up | 233 | 51 (21.9%) | 182 (78.1%) | |
| Anginal status (n = 210) | ||||
| CCS1 | 195 (92.9%) | 40 (27.8%) | 155 (93.4%) | 0.600 |
| CCSII | 9 (4.3%) | 2 (1.4%) | 7 (4.2%) | |
| CCSIII | 5 (2.4%) | 2 (1.4%) | 3 (1.8%) | |
| CCSIV | 1 (0.5%) | 0 (0.0%) | 1 (0.6%) | |
| Myocardial infarction (n = 221) | ||||
| No | 217 (98.2%) | 46 (97.9%) | 171 (98.3%) | 1.000 |
| Yes | 4 (1.8%) | 1 (2.1%) | 3 (1.7%) | |
| Stroke (n = 228) | ||||
| No | 224 (98.2%) | 49 (100.0%) | 175 (98.9%) | 1.000 |
| Yes | 4 (1.8%) | 0 (0.0%) | 2 (1.1%) | |
| Percutaneous coronary intervention | 2 (0.9%) | 1 (2.0%) | 1 (0.6%) | 0.381 |
| Coronary artery bypass surgery | 1 (0.4%) | 1 (2.0%) | 0 (0.0%) | 0.213 |
| Participated in CR (n = 225) | 25 (11.1%) | 3 (6.4%) | 22 (12.3%) | 0.307 |
| Medications | ||||
| Aspirin | 162 (79.8%) | 40 (85.1%) | 122 (78.2%) | 0.407 |
| Other antiplatelets agents | 115 (56.9%) | 24 (51.1%) | 91 (58.7%) | 0.402 |
| Anticoagulant | 23 (11.6%) | 4 (8.7%) | 17 (11.1%) | 0.788 |
| Beta-blocker | 134 (66.3%) | 30 (65.2%) | 104 (66.7%) | 0.861 |
| ACE-I | 58 (28.9%) | 15 (33.3%) | 43 (27.6%) | 0.460 |
| ARB | 17 (8.4%) | 6 (13.0%) | 11 (7.1%) | 0.227 |
| Statin | 171 (84.7%) | 36 (78.3%) | 135 (86.5%) | 0.171 |
| Atrial fibrillation | ||||
| Patients with data at 6 months follow-up | 205 | 111 (54.1%) | 94 (45.9%) | |
| Repeat echocardiogram (n = 194) | 12 (6.2%) | 5 (4.8%) | 7 (8.0%) | 0.386 |
| Ejection fraction (%) (n = 12) | ||||
| <30 | 3 (25.0%) | 0 (0.0%) | 3 (42.9%) | 0.189 |
| 40-50 | 3 (25.0%) | 2 (40.0%) | 1 (14.3%) | |
| 51-60 | 4 (33.3%) | 3 (60.0%) | 1 (14.3%) | |
| >60 | 2 (16.7%) | 0 (0.0%) | 2 (28.6%) | |
| Medication (n = 189) | ||||
| Anticoagulation | 115 (60.8%) | 67 (65.0%) | 48 (55.8%) | 0.232 |
| Venous thromboembolism | ||||
| Patients with data at 6 months follow-up | 372 | 249 (66.9%) | 123 (33.1%) | |
| Bleeding complication | 2 (0.5%) | 0 (0.0%) | 2 (1.6%) | 0.109 |
| Hemoglobin drop >2 units (n = 143) | 4 (2.8%) | 1 (1.1%) | 3 (5.8%) | 0.139 |
| Recurrent venous thromboembolism (n = 333) | 3 (0.9%) | 2 (0.9%) | 1 (0.9%) | 1.000 |
| Post-thrombotic syndrome | 3 (0.8%) | 1 (0.4%) | 2 (1.7%) | 0.257 |
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CCS = Canadian Cardiovascular Society; DOAC = direct oral anticoagulant; MRA = mineralocorticoid receptor agonists; other abbreviations as in Table 4.
Acute coronary syndrome
At 6-month follow-up, 8 patients with ACS had recurrent cardiovascular events, 4 myocardial infarction, and 4 stroke, with no statistically significant sex difference. There were no sex differences in secondary prevention medication use, with 79.8% on aspirin, 66.3% on a beta-blocker, 37.3% on ACEI/ARB, and 84.7% on a statin. Overall, only 25 patients with ACS (11.1%) participated in CR with no significant sex differences in participation (Table 6).
Venous thromboembolism
Among patients with VTE, 3 (0.9%) experienced recurrence, with no significant sex difference. There was also no significant sex difference in the occurrence of other complications, including bleeding, drop in hemoglobin, and post-thrombotic syndrome (Table 6).
Sex differences in mortality
In-hospital mortality
Overall, 1,240 of the 1,241 patients admitted had their data available for assessment of clinical outcome at discharge. In-hospital mortality occurred in 7.4% of patients (8.0% among women vs 6.9% among men; P = 0.449).
Six-month mortality
At 6 months, follow-up data were obtained for the 446 outpatients and 1,148 who were alive at discharge, yielding outcome data for a total of 1,594. The 6-month mortality rate was 14.7% overall (14.8% in women vs 14.5% in men, P = 0.881). In subgroup analysis, 6-month mortality was highest among patients with HF (21.1% in both women and men), followed by VTE (9.6% in women vs 11.4% in men; P = 0.716), AF (10.8% vs 14.9%; P = 0.406), and ACS (2.0% vs 4.4%; P = 0.688) (Table 7).
Table 7.
In-Hospital and 6-Month Mortality by Sex
| Overall | Female | Male | P Value | |
|---|---|---|---|---|
| In-hospital (n = 1,240) | 92 (7.4%) | 47 (8.0%) | 45 (6.9%) | 0.449 |
| 6-month mortality (n = 1,526) | ||||
| Overall | 224 (14.7%) | 117 (14.8%) | 107 (14.5%) | 0.881 |
| By diagnosis | ||||
| Heart failure | 151 (21.1%) | 80 (21.1%) | 71 (21.1%) | 1.000 |
| Acute coronary syndrome | 9 (3.9%) | 1 (2.0%) | 8 (4.4%) | 0.688 |
| Atrial fibrillation | 26 (12.7%) | 12 (10.8%) | 14 (14.9%) | 0.406 |
| Venous thromboembolism | 38 (10.2%) | 24 (9.6%) | 14 (11.4%) | 0.716 |
After adjustment for age, ethnicity, income, and BMI, no significant sex differences were observed in either in-hospital mortality (adjusted OR: 0.73; 95% CI: 0.44-1.21; P = 0.227) or 6-month mortality (adjusted OR: 1.02; 95% CI: 0.69-1.50; P = 0.927). Similar findings were observed across all diagnostic subgroups (Table 8). Sex-based differences in clinical characteristics, treatment, outcomes, and mortality are summarized in the Central Illustration.
Table 8.
Adjusted In-Hospital and 6-Month Mortality by Sex
| Predictor | Adjusted OR | 95% CI | P Value | |
|---|---|---|---|---|
| In-hospital mortality (n = 1,240) | ||||
| Overall | Female sex | 0.73 | 0.44-1.21 | 0.227 |
| Heart failure | Female sex | 0.54 | 0.25-1.20 | 0.129 |
| Acute coronary syndrome | Female sex | 0.61 | 0.26-1.42 | 0.251 |
| Atrial fibrillation | Female sex | 1.00 | 0.06-15.78 | 0.995 |
| Venous thromboembolism | Female sex | 1.58 | 0.35-7.09 | 0.548 |
| 6-month mortality (n = 1,526) | ||||
| Overall | Female sex | 1.02 | 0.69-1.50 | 0.927 |
| Heart failure | Female sex | 1.30 | 0.80-2.10 | 0.297 |
| Acute coronary syndrome | Female sex | 0.85 | 0.35-2.05 | 0.713 |
| Atrial fibrillation | Female sex | 0.63 | 0.05-8.12 | 0.719 |
| Venous thromboembolism | Female sex | 0.33 | 0.09-1.11 | 0.074 |
Adjusted for age, ethnicity, income, and BMI.
Abbreviation as in Table 1.
Central Illustration.
Sex Differences in Cardiovascular Disease in Kenya
The illustration summarizes sex differences in cardiovascular risk profile, clinical presentation, diagnosis, treatment, and clinical outcomes among patients enrolled in the Kenya Heart Registry, a longitudinal survey of individuals diagnosed with heart failure (HF), acute coronary syndrome (ACS), venous thromboembolism (VTE), and atrial fibrillation (AF) between 2019 and 2023. Women were younger and more likely to present with venous thromboembolism, heart failure with preserved ejection fraction (HFpEF), and hypertensive heart disease. Men were more likely to smoke, consume alcohol, and present with acute coronary syndrome or alcoholic cardiomyopathy. No significant sex differences were observed in diagnostic investigations, treatment strategies (medications and interventions), in-hospital mortality, and 6-month mortality.
Discussion
This Kenyan study examined the sex differences in demographics, clinical presentation, cardiovascular risk profiles, diagnosis, treatment, and clinical outcomes of 1,687 participants included in the Kenya Heart Registry. HF represented the most common cause of presentation, followed by VTE, ACS, and AF. Overall, our findings indicate significant sex-based differences in the risk factors, etiology, and presentation, but no difference in treatment and clinical outcomes.
The analysis of the overall mean age at presentation showed that females were younger than males (mean age of 50.9 vs 54.2 years; P < 0.001). This was most likely related to the fact that VTE presentations occurred at a much younger age in females than in males (44.2 vs 51.1 years; P < 0.001). Females tended to be in the lower income group compared to males (P < 0.001). Tromp J et al reported similar findings in the REPORT-HF (International REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) registry. This was a global longitudinal cohort study that enrolled HF patients from 44 countries across 6 continents between July 2014 and March 2017.2
Smoking and alcohol use were significantly more prevalent among males, calling for increased focus and interventions to address these risk factors in this population. In addition, slightly above half of this population was overweight or obese, calling for greater emphasis on the prevention and management of this risk factor.
Heart failure
Our data revealed a mean age of 52 years at presentation for HF, with no significant sex difference between males and females. This finding suggests that HF occurs at similar ages in both sexes, although the underlying causes and clinical presentation differ. Notably, similarly to prior studies, such as the report by Owen et al,10 female patients had a higher LV ejection fraction compared to males (P < 0.001), with a higher proportion of females with HFpEF compared to males, consistent with other studies, particularly in the middle-aged to elderly demographic.9 HFpEF is often associated with other comorbid conditions, such as hypertension, which was also more prevalent in females compared with males in this cohort.
Contrary to evidence from Europe and North America, where ischemic heart disease is the primary etiology of HF,11 the most common etiologies of HF in our study were dilated cardiomyopathy, hypertensive heart disease, and rheumatic heart disease. Female patients in our cohort were more likely to have hypertensive heart disease, while males had a higher prevalence of alcoholic cardiomyopathy. This sex difference is consistent with previous studies that demonstrate a higher prevalence of alcohol-related heart disease in males.12 Although women had a higher prevalence of hypertensive heart disease, there were no significant sex-based differences in systolic or diastolic blood pressure at presentation. Blood pressure readings at a single time point may not fully reflect the long-term burden of hypertension or its contribution to hypertensive heart disease, particularly as they can be influenced by factors such as ongoing treatment and adequacy of blood pressure control.
There was a higher proportion of males than females in the HF with reduced ejection fraction subgroup owing to higher rates of alcoholic, ischemic, and dilated cardiomyopathy presentations in males than females. Of note, peripartum cardiomyopathy, a HF etiology specific to females, represented 4.5% of the HF cohort. The observed difference in the etiology of HF underscores the importance of considering sex-specific risk factors in the prevention and management of HF.
Although there was no significant sex difference in NYHA functional class at presentation, females reported greater limitation in activities of daily living. Previous studies have reported higher prevalence of HF symptoms, such as dyspnea, among females.2,13 Although not reported in this study, this could explain the difference in limitation.
There were no observed sex differences in the use of pharmacological or device-based HF treatments. Similar findings have been reported in other studies, which noted comparable prescription rates of renin–angiotensin system inhibitors and beta-blockers between men and women, but lower use of MRAs and cardiac devices among women.2 Access to newer therapies such as angiotensin receptor–neprilysin inhibitors, sodium glucose co-transporter-2 inhibitors, and glucagon-like peptide-1 receptor agonists was limited to very few patients during the study period. These drugs were not included in the local guidelines for management of HF at the time, which is why related data were not collected.
At 6 months follow-up, most HF patients had improved functional class and reported fewer limitations in activities of daily living. There were no sex differences in these outcomes or in mortality, which is encouraging as it suggests that the prognosis for females and males with HF may be similar when managed appropriately. This observation confirms earlier published data from the global variations according to sex in patients hospitalized for HF in the REPORT-HF registry by Tromp J et al.2
Acute coronary syndrome
Our analysis explored the clinical presentation and management of ACS in both sexes. We observed that females with ACS were older at presentation, which is consistent with prior research/literature that suggests that there might be some hormonal protective mechanisms in premenopausal females that disappear after menopause.14
Although females had a higher prevalence of hypertension and diabetes, which are well-established risk factors for ACS, they were less likely to be smokers and less likely to be on statin therapy at admission. These findings highlight significant sex differences in ACS risk factors and treatment, which may contribute to variations in outcomes.
In terms of coronary assessment, the rate of coronary angiography and angioplasty procedures was similar in both sexes. This contradicts prior studies in the Western world, where males are more likely to be referred for angiography and receive more interventional therapies for coronary artery disease compared with females.8 These procedures remain prohibitively expensive for many African patients, and due to the high out-of-pocket health expenditure in the region, access is often limited to those who can afford to pay for them directly. It also implies that some cases of ischemic cardiomyopathy as an etiology of HF might have been missed since only a few patients had invasive or CT-based coronary angiograms performed.
Furthermore, despite a high rate of coronary angiography (85% of ACS presentations) and PCI (75% of ACS presentations) across both sexes, there were no significant differences in treatment between males and females, which suggest equitable management.
With regard to secondary prevention, there was no sex difference in uptake of the 4 drug pillars of secondary prevention—antiplatelets/anticoagulants, beta-blockers, Renin -Angiotensin -Aldosterone System (RAAS) inhibitors, and statins at 6 months. However, overall uptake of these therapies was suboptimal as reported in studies conducted in both low- and high-income countries.15 It remains concerning that only 11% of patients with ACS were referred for CR, a missed opportunity to improve long-term outcomes, particularly given the known benefits of rehabilitation in reducing mortality and rehospitalization rates.15 Class 1 recommendations for referral to CR include myocardial infarction, PCI, coronary artery bypass graft, chronic stable angina, HF, peripheral arterial disease, and CVD prevention.15 Females had CR lower participation rates (12.3% vs 6.4%), though not statistically significant. These findings are similar to other studies, which have reported low uptake of CR globally.15
Atrial fibrillation
In the AF cohort, the diagnostic modality was a standard 12-lead ECG in 99.1%. While this may seem convenient, it overlooks the fact that some cases of AF might be missed because, in Africa, there is relatively limited use of other diagnostic methods such as ambulatory ECG monitors, event recorders, or device therapy. Further research is necessary to determine the true rate of AF and how the appropriate use of all diagnostic modalities could improve the diagnosis and treatment outcomes of AF.
In this cohort, we also observed that more females presented with permanent AF, while more males presented with paroxysmal AF. This sex difference in AF type may reflect sex-based differences in disease progression and underlying comorbidities, like hypertension and HF. Additionally, it could be due to delays in diagnosis among females. The relationship between AF and stroke was not significantly different between the sexes, possibly because of the very short follow-up time; although the higher frequency of permanent AF in females may increase their stroke risk, it highlights the need for more aggressive management strategies in this group.
Venous thromboembolism
Our study also found sex-based differences in the presentation of VTE. Females were significantly younger at presentation compared to males. They had a higher likelihood of presenting with deep venous thrombosis, while males were more likely to present with pulmonary embolism. This finding may be explained by the fact that young, premenopausal females are more predisposed to VTEs than men due to sex-specific risk factors such as pregnancy, oral contraceptive use, and hormonal therapy.16 Conversely, pulmonary embolism, which is more common in males, could reflect higher rates of associated risk factors like smoking and chronic conditions such as renal insufficiency. The absence of a predisposing factor for VTE was more common in males, raising important questions about the role of undiagnosed or unknown risk factors in this population. Studies have reported a higher intrinsic risk of VTE related to factors such as age, height, comorbidities, and genetics, which require further exploration.17
Overall data
In this study, the overall mortality rate, both in-hospital (7.4%) and at 6-month follow-up (14.7%), is relatively high compared to reported rates in other countries.18 The 6-month disease-specific mortality was highest among patients presenting with HF (21.1%). In this cohort, sex was not an independent predictor of in-hospital or 6-month mortality after adjustment for age, ethnicity, income, and BMI. Although women had a lower in-hospital mortality, particularly among patients with HF and VTE, and lower 6-month mortality among those with AF, these differences were not statistically significant. Despite women presenting with a seemingly more favorable clinical profile, including younger age, higher LV ejection fraction, and lower rates of ACS events, clinical outcomes were comparable between men and women. These findings suggest that once access to care and treatment are established, outcomes are largely comparable between men and women in this population. Further studies in a larger cohort to better understand potential sex-related factors influencing these outcomes are needed.
The high mortality rates, especially in those presenting with HF, highlight the urgent need for optimization of Guideline-Directed Medical Therapy (GDMT). Primary prevention strategies must be central to the care of African patients, including early recognition and management of cardiovascular risk factors such as hypertension, excess weight, diabetes, smoking, and alcohol intake. Risk factor management interventions for different CVDs should consider sex-related differences. This study did not collect sex-specific risk factors for women, including adverse pregnancy outcomes, use of oral contraceptives, age at menarche, or menopausal status, all of which are associated with an increased risk of CVDs in women. We are therefore not able to show the association of these sex-specific risk factors with cardiovascular risk, disease presentation, treatment, or outcomes.
We observed that the quality of care for both HF and ACS is far from optimal. For example, we found that <65% of participants received ACEI/ARBs, beta-blockers, or MRAs, which are the cornerstones of GDMT for HF, regardless of sex. Notably, only 11.1% of ACS patients and 1.2% of HF patients were referred for CR. Although there was no sex difference in referral rates for CR, it may be that so few are referred that we could not detect a difference. There is a need to emphasize proper guideline-directed therapy, including medication, device therapy such as implantable cardioverter-defibrillator/cardiac resynchronization therapy, and CR interventions. The findings of this study highlight that sex is an important prognostic factor in this population, where local evidence is scarce. Specifically, these findings underscore the need to tailor prevention strategies to target the most common risk factors in each sex, respectively. For instance, prevention strategies among males in Kenya should emphasize smoking cessation, harmful use of alcohol, and early detection and management of diabetes. Females with HF will need treatment strategies that focus on management of HFpEF as well as GDMT and CR to address their limitations in activities of daily living. Additional strategies include managing the surgery-related VTE risk among females in Kenya. These findings also confirm the need for larger, prospective studies in Kenya to confirm and expand on these observations, including the role of sex-specific risk factors in this population. There is a need to develop policies and guidelines to inform the design of targeted screening and education programs and training curricula that address the unique needs of Kenyan women and men with CVDs.
Study limitations
This study has several limitations. Convenience sampling was used during the recruitment of patients into the registry, and therefore, the potential selection bias may limit the generalizability of the findings. The observational nature of the data prevents the establishment of causal relationships. There are no data on the uptake of newer medications with documented survival benefit, which could help explain why the mortality rates are higher than expected. Additionally, the underdiagnosis of ischemic heart disease in the HF cohort, due to limited access to coronary angiography, positron emission tomography/CT, and cardiac CT, may have skewed the etiology of HF.
Another limitation of this study is the lack of standardized protocols and adjudication for echocardiogram and ECG interpretation. Since these investigations were interpreted by the attending physicians at each site, there is a possibility of interobserver variability that could have affected diagnostic consistency across sites. In addition, depressive symptoms were assessed through clinical interviews and self-reports of health status rather than a validated questionnaire, which may have introduced information bias and affected the interpretation of our findings.
Additional limitations are common when using registry data, including missing, incomplete, and erroneous entries. Analyses were based on complete cases, which may limit generalizability. In addition, the 6-month follow-up was collected through a telephone interview and was self-reported, potentially affecting the accuracy and completeness of the data. Lastly, the lack of detailed information on medication adherence and lifestyle changes after discharge limits our understanding of the long-term impact of the treatment strategies.
Conclusions
This study highlights significant sex-based differences in risk factors, etiology, and clinical presentation among patients diagnosed with 4 major CVD—HF, ACS, AF, and VTE—enrolled in the Kenya Heart Registry.
In this cohort, female patients were generally younger and more likely to belong to a lower-income group compared to their male counterparts. Traditional cardiovascular risk factors such as alcohol consumption and smoking were more common among males. Despite the differences in risk profiles and clinical presentation, there were no statistically significant differences between sexes in terms of diagnostic investigations, treatment strategies, or clinical outcomes.
Overall mortality rates—both in-hospital and at 6-month follow-up—were high across the cohort. Additionally, adherence to guideline-directed medical therapies, including pharmacological treatment, device therapy, and CR was low, with no significant sex-based differences observed.
Understanding sex-specific differences in clinical presentation is critical for developing personalized care strategies that can enhance treatment efficacy and patient outcomes. Future research should prioritize sex-specific approaches for primary prevention, diagnosis, treatment, and secondary prevention to ensure optimal cardiovascular care for both men and women in the African context.
Funding support and author disclosures
Funding for this study was received from the National Research Fund, Nairobi, Kenya and Novartis, Basel, Switzerland. None of the funders were involved in data collection, data analysis, and interpretation of findings. Dr Gulati has received Advisory Boards/Consultant Fees/Honoraria from Bayer, New Amsterdam, and Medtronic Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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