The acute heart rate response (AHRR) to physical activity, which refers to the change in heart rate during and after exercise, has been associated with cardiovascular and all-cause mortality. Previous studies have shown that AHRR is significantly determined by genetics in addition to environmental and lifestyle factors. The aim of this study was to investigate the genetic background of AHRR by analysing ten single nucleotide polymorphisms (SNPs) associated with leisure-time physical activity (LTPA) in 620 samples from the Hungarian population. The AHRR can be characterised as the difference between post-exercise and resting heart rate, i.e., the delta heart rate (ΔHR) defined by the YMCA 3 min step test, with a lower value indicating better cardiovascular fitness. The association of SNPs with ΔHR was analysed both separately and in combination using an optimised polygenic score (oPGS). The results showed that five SNPs (rs10252228, rs459465, rs6022999, rs8097348, and rs12405556) had at least nominally significant (p < 0.05) individual associations with ΔHR. After optimizing the PGS, a cumulative effect was observed for eight SNPs (rs6022999, rs12405556, rs459465, rs10252228, rs8097348, rs10887741, rs12612420, and rs7023003) that had a strong and statistically significant association with ΔHR (B = −2.51, 95% CI: −3.46–−1.76; p = 2.99 × 10⁻⁹). Of the four main domains of physical activity, the oPGS showed a significant positive association only with LTPA (B = 84.60; 95%CI: 25.23–143.98; p = 0.005). In conclusion, our results suggest that the SNPs we investigated influence individual leisure-time physical activity, mediated by their effects on the acute heart rate response.

Background/Objectives: As part of the human adaptation to dairy consumption, the presence of the rs4988235-T variant in the MCM6 gene primarily determines lactase persistence in adult European populations, increasing the expression of the lactase-encoding LCT gene. Carriers of the C/C variant are lactose intolerant, while carriers of the T/T or T/C variant have persistent lactase enzyme activity and are able to digest lactose in adulthood. While the association between lactose intolerance and increased cardiovascular risk (CVR) is well-known, the underlying causes have only been partly explored. The present study aimed to investigate the association of rs4988235 polymorphism with significant lipids affecting cardiovascular health and estimated CVR. Methods: The rs4988235 polymorphism was genotyped in 397 subjects from the general Hungarian population and 368 individuals from the Roma population. To characterize the overall lipid profile, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein AI (ApoAI), and apolipoprotein B100 (ApoB100) levels were measured, and their ratios (TG/HDL-C, LDL-C/HDL-C, and ApoB100/ApoAI) were calculated. Cardiovascular risk was estimated using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCE), Revised Pooled Cohort Equations (RPCE), and the Systematic Coronary Risk Evaluations (SCORE and SCORE2) algorithms. Adjusted linear and logistic regression analyses were performed, with p < 0.05 considered significant. Results: The Roma population had a significantly higher prevalence of the C/C genotype than the general population (65.5% vs. 40.3%, respectively). The results of the adjusted linear regression analysis showed a significant association between the C/C genotype and higher LDL-C level (B = 0.126, p = 0.047) and ApoB100 level (B = 0.046, p = 0.013), as well as a higher LDL-C/HDL-C ratio (B = 0.174, p = 0.021) and a higher ApoB100/ApoAI ratio (B = 0.045, p = 0.002), as well as a lower HDL-C level (B = −0.041, p = 0.049). The C/C genotype was also significantly associated with an increased cardiovascular risk (CVR) as estimated by the SCORE (B = 0.235, p = 0.034), SCORE2 (B = 0.414, p = 0.009), PCE (B = 0.536, p = 0.008), and RPCE (B = 0.289, p = 0.045) but not the FRS. After adjusting the statistical model further for ApoAI and ApoB100 levels, the significant correlation with the risk estimation algorithms disappeared (SCORE: p = 0.099; SCORE2: p = 0.283; PCE: p = 0.255; and RPCE: p = 0.370). Conclusions: Our results suggest that the C/C genotype of rs4988235 is associated with significantly higher ApoB100 and lower ApoAI levels and consequently higher ApoB100/ApoAI ratios, potentially contributing to an increased risk of cardiovascular disease. The results of the statistical analyses suggest that the association between lactose intolerant genotype and cardiovascular risk may be mediated indirectly via modification of the apolipoprotein profile.

Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624—C_dominant: B = −8.41, p < 0.001; rs708272—G_dominant: B = −8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624—C_dominant: OR = 0.44, p = 0.004; rs708272—G_dominant: OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3—CAGCA: B = −6.81, p = 0.003; H9—CGGCG: B = −14.64, p = 0.015) and lower risk of adverse AHRR (H3—CAGCA: OR = 0.58, p = 0.040; H9—CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1—AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile.

The association of HDL and its subfractional profile with cardiovascular health, particularly atherosclerosis, is well established; however, its association with post-exercise heart rate response remains underexplored. This cross-sectional study investigated whether HDL subfraction distribution is associated with post-exercise heart rate dynamics. We analyzed 304 adults, stratifying HDL into ten subfractions and 3 subclasses using the Lipoprint^® system. Heart rate was measured at rest (HR_rest), immediately after the YMCA 3-min step test (HR_aft), and during recovery (HR_5min and HR_10min) to calculate ΔHR. Multiple regressions were applied with False Discovery Rate correction. Participants with a more favorable post-exercise heart rate profile exhibited higher ApoA-I levels and favorable lipid ratios. Subfractions spanning the large and intermediate ranges (HDL-3 to HDL-5) were inversely associated with HR_aft, HR_5min, and ΔHR. In contrast, smaller, lipid-poor subfractions (HDL-7 to HDL-10) were associated with higher heart rates and a less favorable post-exercise response. Total HDL-C and subclass-level concentrations showed no significant association. These findings suggest that HDL particle size distribution may provide exploratory insight into exercise-related cardiovascular responses beyond conventional lipid metrics. Although limited by the use of a submaximal field test and manual heart rate assessment, these results support further investigation of HDL subfraction profiling in relation to post-exercise heart rate dynamics.

Smoking has a well-established impact on cardiovascular health, notably through elevated resting heart rate and impaired autonomic regulation—both key risk factors. While nicotine’s acute effects are well documented, the influence of smoking-related genetic variants on heart rate (HR) responses remains unclear. This study investigated the association between selected smoking-related single nucleotide polymorphisms (SNPs) and HR dynamics following physical exertion. A total of 661 Hungarian adults completed the YMCA 3 min step test, with HR measured at rest, immediately post-exercise, and during recovery at 5 and 10 min. Key indices included post-exercise HR (HR_aft), HR change (ΔHR), maximum HR percentage (HR_max%), and heart rate recovery coefficient (HRR). Genetic analysis focused on nine SNPs previously linked to smoking behaviours, with a composite genetic risk score derived from the three most influential variants (rs2235186, rs4142041, and rs578776). Associations were examined using adjusted linear regression. No significant relationship was found between any individual SNP and resting HR. However, rs2235186, rs4142041, and rs578776 were consistently associated with elevated HR_aft, increased ΔHR, higher HR_max%, and slower HRR. The genetic risk score showed significant correlations with all post-exercise HR measures, suggesting a cumulative genetic effect. These findings indicate that smoking-related genetic predisposition may influence autonomic cardiovascular responses to physical activity. Although resting HR remains unaffected, specific SNPs are linked to post-exercise HR dynamics and recovery, highlighting the potential value of genetic screening in personalised cardiovascular risk assessment among smokers.

Regular physical activity (PA) is strongly associated with cardiovascular health; however, its associations with cardiovascular function may differ according to the domain, intensity, and context in which it is performed. This exploratory cross-sectional study investigated associations between domain- and intensity-specific PA and heart rate (HR) responses to standardized exercise in 605 adults from northeastern Hungary. Participants had a mean age of 42.50 ± 12.23 years, 65.5% were women, and 60.7% were overweight or obese. PA was assessed using the long-form IPAQ, and HR responses were evaluated using the YMCA 3 min step test. Multiple linear regression models were adjusted for demographic, clinical, behavioural, and socioeconomic covariates, with genetic scores examined in sensitivity analyses. Higher total PA was associated with lower ΔHR, HR_aft, and HR_max% (standardized β = −0.222 to −0.207; all q < 0.001). Moderate-intensity PA showed the strongest intensity-specific associations (β = −0.237 to −0.223; all q < 0.001), whereas vigorous PA was associated only with ΔHR after FDR correction, and walking PA showed no significant associations. In the mutually adjusted domain model, leisure-time and domestic/gardening PA were each associated with lower values of all three principal HR outcomes, whereas work- and transport-related PA were not. Exploratory activity-specific associations for cycling, vigorous gardening, and moderate leisure-time PA did not remain significant after FDR correction. These exploratory findings suggest that the intensity and domain composition of habitual PA may be relevant to its associations with post-exercise HR measures and warrant further investigation in independent studies.