{
  "abstract": "Background High blood pressure (BP) leads to coronary artery disease, yet the impact of life course BP on later-life myocardial blood flow (MBF) and perfusion reserve (MPR) remains elusive. In this study, we aimed to explore the link between life course BP and older-age global stress MBF normalized ( STRESSMBFgN) to contemporaneous rate pressure product (RPP, where RPP = heart rate x central aortic systolic BP [SBP]) and global MPRg.Methods National Survey of Health and Development (NSHD) is a 1946 birth cohort with continuous follow-up. MyoFit46 recruited ~500 NSHD participants for a cardiovascular magnetic resonance (CMR) scan at 74–78 years, assessing left ventricular (LV) structure and function, perfusion ( STRESSMBFgN and MPRg), and late gadolinium enhancement (LGE). BPs were recorded at 36, 43, 53, 60–64, 69, and 74–78 years. BP step changes between two ages, BP trajectories, mean life course BPs, and areas under the BP trajectory curve (AUC-BP) were derived using a mixed-effects natural cubic spline model. Participants were clustered based on their BP trajectories using a latent class mixed model. Associations between these BPs and CMR metrics were tested using generalized linear and additive models (GLMs, GAMs), adjusted for demographics, lifestyle, comorbidities, and antihypertensive use. Mediation analyses explored mechanistic pathways.Results 459 MyoFit46 participants aged 74–78 (53% male) were included. Using GLMs, each 1 mmHg SBP increase at 43, 53, 60–64, 69, and 74–78 years independently associated with a 0.2–0.6% lower STRESSMBFgN (table 1). For 53–69 years SBPs, relationships were non-linear using GAMs, with the steepest STRESSMBFgN decrease observed as SBP rose from 120 to 140mmHg (figure 1). Each 1 mmHg rise in mean life course SBP associated with a 0.9% lower STRESSMBFgN, while each decade spent at 10 mmHg higher SBP (as per AUC-SBP) associated with a 2.1% lower STRESSMBFgN (p<0.001). Each 1 mmHg SBP rise from 43 to 53 years, and from 53 to 60–64 years, was linked to a 0.3% and 0.5% lower STRESSMBFgN respectively, independent of AUC-SBP (table 2). LV maximal wall thickness (WT) mediated 12–17% of the relationships between life course SBPs and STRESSMBFgN. STRESSMBFgN mediated 21–31% of the SBPs-LV LGE associations. Results were similar when using MPRg (tables 1 and 2), STRESSMBFg (not normalized), or after excluding those on antihypertensives. Figure 2 shows participant clusters based on BP trajectories. Those with steep SBP increases from 36 to 53 years and slower increases after (red line) had worse MPRg (2.5 vs 2.9, p=0.046) compared to those with stable SBPs until 60–64 years, followed by steep increases (orange line). Effect sizes were larger for diastolic and pulse pressures.Abstract 6-024 Table 1Associations between life course blood pressure and myocardial perfusion at 74–78 years STRESSMBFgN at 74–78 years MPRg at 74–78 years Age when BP measured % decrease (95% CI) p-value % decrease (95% CI) p-value Systolic BP 36 years 0.14% (-0.10, 0.38) 0.252 -0.01% (-0.24, 0.23) 0.959 43 years 0.23% (0.01, 0.47) 0.045 0.22% (0.02, 0.42) 0.033 53 years 0.32% (0.15, 0.49) <0.001 0.22% (0.06, 0.39) 0.009 60–64 years 0.51% (0.35, 0.68) <0.001 0.37% (0.21, 0.53) <0.001 69 years 0.58% (0.37, 0.78) <0.001 0.32% (0.12, 0.52) 0.002 74–78 years 0.42% (0.25, 0.59) <0.001 0.15% (-0.01, 0.31) 0.071 Diastolic BP 36 years 0.08% (-0.21, 0.37) 0.575 0.07% (-0.20, 0.34) 0.603 43 years 0.08% (-0.21, 0.37) 0.557 0.08% (-0.19, 0.35) 0.556 53 years 0.52% (0.22, 0.83) <0.001 0.23% (-0.07, 0.53) 0.131 60–64 years 0.94% (0.64, 1.25) <0.001 0.50% (0.20, 0.80) 0.001 69 years 0.70% (0.34, 1.04) <0.001 0.16% (-0.17, 0.49) 0.339 74–78 years 0.53% (0.25, 0.81) <0.001 -0.01% (-0.27, 0.25) 0.935 All reported analyses consisted of generalized linear models with a gamma distribution and log link. Regression coefficients represent the decrease in STRESSMBFgN or MPRg per 1mmHg increase in the corresponding BP. All models were adjusted for age, sex, socioeconomic position, BMI, smoking status, alcohol consumption, physical activity, the presence of diabetes, and use of antihypertensives at the corresponding age. Significant p-values in bold.BMI = body mass index, BP = blood pressure, CI = confidence interval, MPRg = global myocardial perfusion reserve, STRESSMBFgN = global stress myocardial blood flow normalized to contemporaneous rate pressure product (calculated as the product of heart rate and central aortic SBP).Abstract 6-024 Table 2Associations between step changes in blood pressure across the life course and myocardial perfusion at 74–78 years STRESSMBFgN at 74–78 years MPRg at 74–78 years Step change in BP between two ages % decrease (95% CI) p-value % decrease (95% CI) p-value Systolic BP 36 to 43 years 0.22% (-0.04, 0.47) 0.090 0.11% (-0.13, 0.36) 0.361 43 to 53 years 0.29% (0.10, 0.49) 0.004 0.22% (0.02, 0.41) 0.033 53 to 60–64 years 0.51% (0.30, 0.73) <0.001 0.35% (0.15, 0.56) <0.001 60–64 to 69 years 0.31% (0.06, 0.56) 0.018 0.09% (-0.16, 0.33) 0.473 69 to 74–78 years 0.26% (0.07, 0.44) 0.006 0.05% (-0.13, 0.23) 0.559 Diastolic BP 36 to 43 years 0.07% (-0.25, 0.39) 0.656 -0.04% (-0.35, 0.28) 0.819 43 to 53 years 0.59% (0.25, 0.92) <0.001 0.25% (-0.09, 0.59) 0.149 53 to 60–64 years 0.93% (0.54, 1.32) <0.001 0.53% (0.15, 0.89) 0.006 60–64 to 69 years 0.23% (-0.17, 0.63) 0.256 -0.12% (-0.50, 0.25) 0.540 69 to 74–78 years 0.35% (0.04, 0.5) 0.026 -0.08% (-0.37, 0.20) 0.562 All reported analyses consisted of generalized linear models with a gamma distribution and log link. Regression coefficients represent the decrease in STRESSMBFgN or MPRg per 1mmHg increase in BP at age 2 compared to age 1. All models were adjusted for age, sex, socioeconomic position, BMI, smoking status, alcohol consumption, physical activity, the presence of diabetes, the use of antihypertensives, baseline BP (i.e., BP at age 1), and area under the BP trajectory across the life course (calculated using a linear-mixed model as described in the abstract). Significant p-values in bold.BMI = body mass index, BP = blood pressure, CI = confidence interval, MPRg = global myocardial perfusion reserve, STRESSMBFgN = global stress myocardial blood flow normalized to contemporaneous rate pressure product (calculated as the product of heart rate and central aortic SBP).Abstract 6-024 Figure 1Relationships between SBPs across the life course and STRESSMBFgN at 74–78 years.Generalized additive models explored any non-linear relationships between SBPs at 53, 60–64, and 69 years (expressed in mmHg) and STRESSMBFgN at 74–78 years(expressed in 10-4 ml/min*g*mmHg*bpm), after adjusting for age, sex, socioeconomic position, BMI, smoking status, alcohol consumption, physical activity, the presence of diabetes, and antihypertensive use at the corresponding age. Significant p-values in bold. EDF ~1 implies a linear relationship, while EDF >1 suggests the presence of non-linearities.BMI = body mass index, bpm = beats per minute, EDF = estimated degrees of freedom, STRESSMBFgN = global stress myocardial blood flow normalized to contemporaneous rate pressure product (calculated as the product of heart rate and central aortic SBP), SBP = systolic blood pressure.Abstract 6-024 Figure 2MyoFit46 participant clusters based on life course BP trajectoriesIn MyoFit46 participants, BPs were recorded at 36, 43, 53, 60–64, 69, and 74–78 years (vertical dotted black lines). A latent class mixed model using natural cubic splines and 43, 53, 60–64, and 69 years as knots, grouped study members into clusters based on their life course BP trajectories, with separate analyses conducted for systolic and diastolic BPs. This model identified 3 different clusters based on life course systolic BP trajectories (shown in green, orange, and red in panel A) and 2 clusters when using diastolic BPs (shown in green and orange in panel B), displayed using bold lines. Individual participant trajectories are also shown using thin lines.BP = blood pressure.Conclusion Higher life course BPs, steeper increases, and spending more years with a higher BP associate with worse myocardial perfusion in older-age, partially explained by high BP increasing LV WT. Reduced myocardial perfusion associates with fibrosis, suggesting that certain individuals (e.g., those with higher midlife BP) may benefit from stricter control.",
  "authors": [
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK"
      ],
      "name": "Constantin-Cristian Topriceanu"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Matthew Webber"
    },
    {
      "affiliations": [
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Hunain Shiwani"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Fiona Chan"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Emma Martin"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Debbie Falconer"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Jonathan Bennett"
    },
    {
      "affiliations": [
        "ELEM Biotech SL, Barcelona, Spain"
      ],
      "name": "Pablo Gonzales"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK",
        "ELEM Biotech SL, Barcelona, Spain",
        "Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK",
        "National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA",
        "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK"
      ],
      "name": "Haytham Shah"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK",
        "ELEM Biotech SL, Barcelona, Spain",
        "Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK",
        "National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA",
        "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK"
      ],
      "name": "Andrew Wong"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK",
        "ELEM Biotech SL, Barcelona, Spain",
        "Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK",
        "National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA",
        "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK"
      ],
      "name": "Iain Pierce"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK",
        "ELEM Biotech SL, Barcelona, Spain",
        "Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK",
        "National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA",
        "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK"
      ],
      "name": "Rhodri H Davies"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK",
        "ELEM Biotech SL, Barcelona, Spain",
        "Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK",
        "National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA",
        "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK"
      ],
      "name": "Pier D Lambiase"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Nishi Chaturvedi"
    },
    {
      "affiliations": [
        "National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD, USA"
      ],
      "name": "Peter Kellman"
    },
    {
      "affiliations": [
        "School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK"
      ],
      "name": "Rebecca Hardy"
    },
    {
      "affiliations": [
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "Cardiac MRI Unit, Barts Heart Centre, West Smithfield, London, UK"
      ],
      "name": "James C Moon"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK"
      ],
      "name": "Alun D Hughes"
    },
    {
      "affiliations": [
        "UCL MRC Unit for Lifelong Health and Ageing, University College London, London, UK",
        "UCL Institute of Cardiovascular Science, University College London, London, UK",
        "The Royal Free Hospital, Centre for Inherited Heart Muscle Conditions, Cardiology Department, Pond Street, Hampstead, London, UK"
      ],
      "name": "Gabriella Captur"
    }
  ],
  "title": "6-024 Higher blood pressure across the life course can be linked to reduced myocardial perfusion in older age",
  "uid": "a69413a2-6d40-595e-997c-d4f6e24cf96c"
}